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AzTrials

NeoplasmsPhase 1NCT03307785

Study of Niraparib, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy in Combination With TSR-042

A Phase 1 study testing Niraparib, TSR-042 and Carboplatin-Paclitaxel in people with Neoplasms and Metastatic Cancer, run by Tesaro, Inc. at 8 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

Part A: To test the safety and tolerability of combination therapy with Niraparib and TSR-042 and to establish a safe dose that will be used in a Phase 2 study. Part B: To test the safety and tolerability of combination therapy with Carboplatin-Paclitaxel and TSR-042 and to establish a safe dose that will be used in a… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Neoplasms, Metastatic Cancer, Advanced Cancer
What is being tested?
Niraparib, TSR-042 and Carboplatin-Paclitaxel
Could I receive a placebo?
No, everyone receives an active treatment
How many people
60 participants
Where
8 sitesUnited States
Study dates
12 Oct 2017to 11 Dec 2024
Phase
Phase 1
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patient has histologically or cytologically proven advanced (unresectable) or metastatic cancer as outlined below according to study part and disease type:
  • Part A: Patients with previously treated advanced or metastatic cancer. Patient may have received no more than 4 lines of treatment for advanced or metastatic cancer. Hormonal treatment will not be considered a prior line of treatment.
  • Part B: Patients with advanced or metastatic cancer for which treatment with carboplatin-paclitaxel is considered appropriate therapy. Patient may have received no more than 1 prior line of chemotherapy in the metastatic setting. Hormonal treatment will not be considered a prior line of treatment.
  • Part C: Patients with previously treated advanced or metastatic cancer. Patient may have received no more than 4 lines of treatment for advanced or metastatic cancer. Hormonal treatment will not be considered a prior line of treatment.
  • Part D: Patients in whom carboplatin-paclitaxel and bevacizumab is considered appropriate therapy. Patient may have received no more than 1 prior line of chemotherapy in the metastatic setting. Hormonal treatment will not be considered a prior line of treatment.
  • Part E and F: Patients who have not received prior systemic therapy, including targeted therapy and biologic agents, for their advanced or metastatic (Stage ≥ IIIB or IV) Non-Squamous NSCLC. Patients who have received neoadjuvant or adjuvant therapy are eligible as long as development of advanced or metastatic disease occurred at least 12 months after completion of neoadjuvant or adjuvant therapy.
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  • Part G, H, and I: Patients who have not received prior systemic therapy, including targeted therapy and biologic agents, for their advanced or metastatic (Stage ≥ IIIB or IV) NSCLC. Patients who have received neoadjuvant or adjuvant therapy are eligible as long as development of advanced or metastatic disease occurred at least 12 months after completion of neoadjuvant or adjuvant therapy.
  • Patient has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
  • Patient has adequate organ function.
  • Female patient has a negative serum pregnancy test within 72 hours prior to taking study treatment if of childbearing potential and agrees to abstain from activities that could result in pregnancy from screening through 180 days after the last dose of study treatment, or is of non-childbearing potential.
  • Male patient agrees to use an adequate method of contraception and not donate sperm starting with the first dose of study treatment through 90 days after the last dose of study treatment. Note: Abstinence is acceptable if this is the established and preferred contraception for the patient.
  • Patient has measurable lesions by RECIST v1.1.
  • For Part A and C, in addition to the general inclusion criteria, patients must also meet the following additional criterion to be considered eligible to participate in this study:
  • Patient is able to take oral medications.
  • For patients to be eligible for any parts of the study using niraparib 300 mg as a starting dose, a screening actual body weight ≥ 77 kg and screening platelet count ≥ 150,000 u/L is necessary.
  • Exclusion Criteria: (Patients will not be eligible for the study entry if any of the following criteria are met)
  • Patient has known active central nervous system metastases, carcinomatous meningitis, or both.
  • Patient has a known additional malignancy that progressed or required active treatment within the last 2 years. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin that has undergone potentially curative therapy, or in situ cervical cancer.
  • Patient is considered a poor medical risk due to a serious, uncontrolled medical disorder, nonmalignant systemic disease, or active infection that requires systemic therapy.
  • Patient has a condition (such as transfusion-dependent anemia or thrombocytopenia), therapy, or laboratory abnormality that might confound the study results or interfere with the patient's participation
  • Patient is pregnant or expecting to conceive children within the projected duration of the study, starting with the screening visit through 180 days after the last dose of study treatment.
  • Note: No data are available regarding the presence of niraparib or its metabolites in human milk, or on its effects on the breastfed infant or milk production. Because of the potential for serious adverse reactions in breastfed infants from niraparib, female patients should not breastfeed during treatment with niraparib and for 1 month after receiving the final dose.
  • Patient has a known history of human immunodeficiency virus (type 1 or 2 antibodies).
  • Patient has known active hepatitis B or hepatitis C.
  • Patient has an active autoimmune disease that has required systemic treatment in the past 2 years.
  • Patient has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 including ipilimumab), or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways.
  • Patient has undergone prior treatment with a known PARP inhibitor.
  • Known history or current diagnosis of MDS or AML.
  • Patient has a known hypersensitivity to TSR-042 components or excipients.
  • For Parts B, D, E, F, G, H, and I, patients will not be eligible for study entry if any of the following additional exclusion criterion are met:
  • Patient has a known hypersensitivity to any of the following relevant study treatments: carboplatin, paclitaxel, pemetrexed, nab-paclitaxel, or TSR-022 components or excipients.
  • For Parts C and D only, patients will not be eligible for study entry if the following additional exclusion criterion is met:
  • Patient has clinically significant cardiovascular disease (e.g., significant cardiac conduction abnormalities, uncontrolled hypertension, myocardial infarction, cardiac arrhythmia or unstable angina, New York Heart Association Grade 2 or greater congestive heart failure, serious cardiac arrhythmia requiring medication, Grade 2 or greater peripheral vascular disease, and history of cerebrovascular accident [CVA]) within 6 months of enrollment.
  • Patient has a history of bowel obstruction, including subocclusive disease, related to the underlying disease and history of abdominal fistula, gastrointestinal perforation, or intra abdominal abscesses. Evidence of recto-sigmoid involvement by pelvic examination or bowel involvement on CT scan or clinical symptoms of bowel obstruction.
  • Patient has proteinuria as demonstrated by urine protein: creatinine ratio ≥1.0 at screening or urine dipstick for proteinuria ≥2 (patients discovered to have ≥2 proteinuria on dipstick at baseline should undergo 24-hour urine collection and must demonstrate <2 g of protein in 24 hours to be eligible).
  • Patient is at increased bleeding risk due to concurrent conditions (e.g., major injuries or surgery within the past 28 days prior to start of study treatment, history of hemorrhagic stroke, transient ischemic attack, subarachnoid hemorrhage, or clinically significant hemorrhage within the past 3 months).
  • Patient has a known hypersensitivity to bevacizumab components or excipients.
  • For Parts E and F only, patients will not be eligible for study entry if any of the following additional exclusion criteria are met:
  • Patient is unable to interrupt aspirin or other nonsteroidal ant-inflammatory drugs, other than an aspirin dose ≤ 1.3 g per day, for a 5-day period (8-day period for long -acting agents, such as piroxicam.
  • Patient is unable or unwilling to take folic acid, vitamin B12 supplement.
  • Patient has symptomatic ascites or pleural effusion. A patient who is clinically stable following treatment for these conditions (including therapeutic thoraco- or paracentesis) is eligible.
  • For Parts G, H, and I only, patients will not be eligible for study entry if any of the following additional exclusion criteria are met:
  • Patient has pre-existing peripheral neuropathy that is Grade ≥ 2 by Common Terminology Criteria for Adverse Events (CTCAE) version 4 criteria.
  • For Parts E, F, G, H and I only, patients will not be eligible for study entry if any of the following additional exclusion criteria are met:
  • Patient has interstitial lung disease or a history of pneumonitis that required oral or intravenous glucocorticoids to assist with management.

Who cannot join

None listed.

Trial locations and contacts

8 sites in 1 country.

8 sites in 1 country

United States8 sites

  • GSK Investigational Site

    Canton, Ohio, 44718

  • GSK Investigational Site

    Cleveland, Ohio, 44106

  • GSK Investigational Site

    Encinitas, California, 92024

  • GSK Investigational Site

    Houston, Texas, 77030

  • GSK Investigational Site

    Nashville, Tennessee, 37203

  • GSK Investigational Site

    San Marcos, California, 92069

  • GSK Investigational Site

    Sarasota, Florida, 34232

  • GSK Investigational Site

    Scottsdale, Arizona, 85258

Other trials in United States

About this study

Official title: Phase 1b Dose-Finding Study of Niraparib, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy in Combination With TSR-042 in Patients With Advanced or Metastatic Cancer

Part A: To test the safety and tolerability of combination therapy with Niraparib and TSR-042 and to establish a safe dose that will be used in a Phase 2 study.

Part B: To test the safety and tolerability of combination therapy with Carboplatin-Paclitaxel and TSR-042 and to establish a safe dose that will be used in a Phase 2 study.

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Part C: To test the safety and tolerability of combination therapy with Niraparib, TSR-042 and Bevacizumab and to establish a safe dose that will be used in a Phase 2 study.

Part D: To test the safety and tolerability of combination therapy with Carboplatin-Paclitaxel, TSR-042 and Bevacizumab and to establish a safe dose that will be used in a Phase 2 study.

Part E: To test the safety and tolerability of combination therapy with Carboplatin-Pemetrexed and TSR-042 and to establish a safe dose that will be used in a Phase 2 study.

Part F: To test the safety and tolerability of combination therapy with Carboplatin-Pemetrexed, TSR-022 and TSR-042 and to establish a safe dose that will be used in a Phase 2 study.

Part G: To test the safety and tolerability of combination therapy with Carboplatin-nab-Paclitaxel, TSR-042 and to establish a safe dose that will be used in a Phase 2 study.

Part H: To test the safety and tolerability of combination therapy with Carboplatin-nab-Paclitaxel, TSR-022 and TSR-042 and to establish a safe dose that will be used in a Phase 2 study.

Part I: To test the safety and tolerability of combination therapy with Carboplatin-Paclitaxel, TSR-022 and TSR-042 and to establish a safe dose that will be used in a Phase 2 study.

Being tested
Niraparib, TSR-042, Carboplatin-Paclitaxel, Bevacizumab, TSR-022
Medical subject headings
Neoplasms, Neoplasm Metastasis, Carcinoma, Non-Small-Cell Lung

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • NiraparibDrug

    Also called Zejula

    Niraparib is a potent, orally active PARP1 and PARP2 inhibitor being developed as a treatment for patients with tumors that harbor defects in the homologous recombination DNA repair pathway or that are driven by PARP-mediated transcription factors.

  • TSR-042Drug

    TSR-042 is a humanized monoclonal antibody that binds with high affinity to PD-1 resulting in inhibition of binding to programmed death receptor ligands 1 and 2 (PD-L1 and PD-L2).

  • Carboplatin-PaclitaxelDrug

    Carboplatin in combination with paclitaxel is a chemotherapy treatment that has been shown to be efficacious against a variety of different tumor types, including non-small cell lung cancer [NSCLC], ovarian cancer, endometrial cancer, and head and neck cancer.

  • BevacizumabDrug

    Also called Avastin

    Bevacizumab is a chemotherapy treatment that has been shown to be efficacious against a variety of different cancer types, including colon cancer, lung cancer, glioblastoma, and renal-cell carcinoma. Bevacizumab is in the angiogenesis inhibitor and monoclonal antibody families of medication. It works by slowing the growth of new blood vessels.

  • TSR-022Drug

    TSR-022 is a monoclonal antibody against TIM-3 (also called HAVCR2), an immune checkpoint receptor. Immune checkpoint proteins are molecules that help to regulate the immune system so it does not mistakenly attack healthy cells. However, they can also keep immune cells from recognizing and killing cancer cells.

    TIM-3 is found on the surface of certain T-cells, including tumor-infiltrating T-cells, that have left the bloodstream and migrated into the tumor environment. By binding to and blocking TIM-3, TRS-022 allows for T-cells to become activated so as to enhance T-cell-mediated attacks on tumors. These attacks reduce their growth.

  • Carboplatin-PemetrexedDrug

    Pemetrexed and platinum therapy in combination with pembrolizumab (anti-PD-1 antibody) has proven to be efficacious in a first line setting for nonsquamous NSCLC patients

  • Carboplatin-Nab-PaclitaxelDrug

    Nab-paclitaxel is a formulation of paclitaxel that is indicated for locally advanced or metastatic NSCLC, as first-line treatment in combination with carboplatin in patients who are not candidates for curative surgery or radiation therapy. Nab-paclitaxel has shown increased ORR and time to progression in metastatic breast cancer compared with solvent-based paclitaxel and has shown antitumor activity and improved ORR compared with solvent-based paclitaxel as first-line therapy in patients with NSCLC.

Study groups in NCT03307785
Study groupRoleWhat they receive
Part A: TSR-042 and niraparib 200 mg QDExperimentalPatients will receive TSR-042 500 milligram (mg), intravenous (IV) infusion on Day 1 of every cycle (every 3 weeks [Q3W]) for 4 cycles (each cycle is 21 days); followed by TSR-042 1000 mg, IV infusion on Day 1 of every other cycle (every 6 weeks [Q6W]) beginning on Day 1 of Cycle 5 along with niraparib 200 mg, once daily (QD), orally on Days 1 to 21 repeated Q3W.
Receives: Drug: Niraparib; Drug: TSR-042
Part A: TSR-042 and niraparib 300 mg QDExperimentalPatients will receive TSR-042 500 mg, IV infusion on Day 1 of every cycle (Q3W) for 4 cycles (each cycle is 21 days); followed by TSR-042 1000 mg, IV infusion on Day 1 of every other cycle (Q6W) beginning on Day 1 of Cycle 5 along with niraparib 300 mg, QD, orally on Days 1 to 21 repeated Q3W.
Receives: Drug: Niraparib; Drug: TSR-042
Part B: TSR-042 and carboplatin-paclitaxelExperimentalPatients will receive TSR-042 500 mg, IV infusion on Day 1 of every cycle (Q3W) for 4 cycles (each cycle is 21 days); followed by TSR-042 1000 mg, IV infusion on Day 1 of every other cycle (Q6W) beginning on Day 1 of Cycle 5 along with carboplatin, IV infusion on Day 1 Q3W and paclitaxel 175 milligram per square meter (mg/m^2), IV infusion on Day 1 Q3W administered for 4 to 6 cycles.
Receives: Drug: TSR-042; Drug: Carboplatin-Paclitaxel
Part C: TSR-042, niraparib 200 mg QD and bevacizumabExperimentalPatients will receive TSR-042 500 mg, IV infusion on Day 1 of every cycle (Q3W) for 4 cycles (each cycle is 21 days); followed by TSR-042 1000 mg, IV infusion on Day 1 of every other cycle (Q6W) beginning on Day 1 of Cycle 5 along with niraparib 200 mg administered orally on Days 1 to 21 repeated Q3W and bevacizumab 15 mg/kilogram (kg), IV infusion on Day 1 of every 21-day cycle Q3W for up to 15 months.
Receives: Drug: Niraparib; Drug: TSR-042; Drug: Bevacizumab
Part C: TSR-042, niraparib 300 mg QD and bevacizumabExperimentalPatients will receive TSR-042 500 mg, IV infusion on Day 1 of every cycle (Q3W) for 4 cycles (each cycle is 21 days); followed by TSR-042 1000 mg, IV infusion on Day 1 of every other cycle (Q6W) beginning on Day 1 of Cycle 5 along with niraparib 300 mg administered orally on Days 1 to 21 repeated Q3W and bevacizumab 15 mg/kg, IV infusion on Day 1 of every 21-day cycle Q3W for up to 15 months.
Receives: Drug: Niraparib; Drug: TSR-042; Drug: Bevacizumab
Part D: TSR-042, carboplatin-paclitaxel and bevacizumabExperimentalPatients will receive TSR-042 500 mg, IV infusion on Day 1 of every cycle (Q3W) for 4 cycles (each cycle is 21 days); followed by TSR-042 1000 mg, IV infusion on Day 1 of every other cycle (Q6W) beginning on Day 1 of Cycle 5 along with carboplatin, IV infusion on Day 1 Q3W and paclitaxel 175 mg/m^2, IV infusion on Day 1 Q3W administered for 4 to 6 cycles; and bevacizumab 15 mg/kg, IV infusion on Day 1 of every 21-day cycle Q3W for up to 15 months.
Receives: Drug: TSR-042; Drug: Carboplatin-Paclitaxel; Drug: Bevacizumab
Part E: TSR-042 and carboplatin-pemetrexedExperimentalPatients will receive TSR-042 500 mg, IV infusion on Day 1 of every cycle (Q3W) along with carboplatin, IV infusion on Day 1 Q3W and pemetrexed 500 mg/m^2, IV infusion on Day 1 Q3W (with vitamin supplementation) administered for 6 cycles (each cycle is 21 days).
Receives: Drug: TSR-042; Drug: Carboplatin-Pemetrexed
Part F: TSR-042, TSR-022, and carboplatin-pemetrexedExperimentalPatients will receive TSR-042 500 mg, IV infusion on Day 1 of every cycle (Q3W); and TSR-022 900 mg, IV infusion on Day 1 Q3W along with carboplatin, IV infusion on Day 1 Q3W administered for 5 cycles (each cycle is 21 days); and pemetrexed 500 mg/m^2, IV infusion on Day 1 Q3W (with vitamin supplementation).
Receives: Drug: TSR-042; Drug: TSR-022; Drug: Carboplatin-Pemetrexed
Part G: TSR-042 and carboplatin-nab-paclitaxelExperimentalPatients will receive TSR-042 500 mg, IV infusion on Day 1 of every cycle (Q3W) along with carboplatin, IV infusion on Day 1 Q3W for 4 to 6 cycles (each cycle is 21 days) and nab-paclitaxel 100 mg/m^2, IV infusion on Days 1, 8 and 15 (every week [Q1W]) of every 3 week cycle for 4 to 6 cycles.
Receives: Drug: TSR-042; Drug: Carboplatin-Nab-Paclitaxel
Part H: TSR-042, TSR-022, and carboplatin-nab-paclitaxelExperimentalPatients will receive TSR-042 500 mg, IV infusion on Day 1 of every cycle (Q3W); followed by TSR-022 900 mg, IV infusion on Day 1 Q3W along with carboplatin, IV infusion on Day 1 Q3W for 4 to 6 cycles (each cycle is 21 days) and nab-paclitaxel 100 mg/m^2, IV infusion on Days 1, 8 and 15 (Q1W) of every 3 week cycle for 4 to 6 cycles.
Receives: Drug: TSR-042; Drug: TSR-022; Drug: Carboplatin-Nab-Paclitaxel
Part I: TSR-042, TSR-022, and carboplatin-paclitaxelExperimentalPatients will receive TSR-042 500 mg, IV infusion on Day 1 of every cycle (Q3W); followed by TSR-022 900 mg, IV infusion on Day 1 Q3W along with carboplatin, IV infusion on Day 1 Q3W and paclitaxel 175 mg/m^2, IV infusion on Day 1 Q3W for 4 to 6 cycles (each cycle is 21 days).
Receives: Drug: TSR-042; Drug: Carboplatin-Paclitaxel; Drug: TSR-022

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Part A: Number of Participants With Dose-limiting Toxicity (DLT)

    An event was considered a DLT if it occurred within the first 21 days of treatment, and met one of following DLT criteria:hematologic toxicity- Grade4 thrombocytopenia persists for >=7 days from the time of adverse event(AE) onset, Grade 4 neutropenia, Grade 4 or Grade 3 febrile neutropenia persists for >=7 days, Grade4 or Grade3 anemia requiring blood transfusion, Grade 3 thrombocytopenia associated with clinically significant bleeding, Grade 3 neutropenia associated with infection as described in Common Terminology Criteria for Adverse Events (CTCAE) version 4.0, drug related Grade 3 or 4 non-hematologic toxicity, drug related Grade 3 or 4 nonhematologic laboratory abnormality if any of the following also occur: abnormality leads to hospitalization and abnormality persists for >=7 days from the time of AE onset; drug related toxicity leading to prolonged delay (>2 weeks) in initiating Cycle 2. DLTs were collected during first cycle to establish recommended phase 2 dose (RP2D).

    Measured: 21 days

  2. Part B: Number of Participants With DLT

    An event was considered a DLT if it occurred within the first 21 days of treatment, and met one of following DLT criteria:hematologic toxicity- Grade4 thrombocytopenia persists for >=7 days from the time of AE onset, Grade 4 neutropenia, Grade 4 or Grade 3 febrile neutropenia persists for >=7 days, Grade4 or Grade3 anemia requiring blood transfusion, Grade 3 thrombocytopenia associated with clinically significant bleeding, Grade 3 neutropenia associated with infection as described in CTCAE version 4.0, drug related Grade 3 or 4 non-hematologic toxicity, drug related Grade 3 or 4 nonhematologic laboratory abnormality if any of the following also occur: abnormality leads to hospitalization and abnormality persists for >=7 days from the time of AE onset; drug related toxicity leading to prolonged delay (>2 weeks) in initiating Cycle 2. DLTs were collected during first cycle to establish RP2D.

    Measured: 21 days

  3. Part C: Number of Participants With DLT

    An event was considered a DLT if it occurred within the first 21 days of treatment, and met one of following DLT criteria:hematologic toxicity- Grade4 thrombocytopenia persists for >=7 days from the time of AE onset, Grade 4 neutropenia, Grade 4 or Grade 3 febrile neutropenia persists for >=7 days, Grade4 or Grade3 anemia requiring blood transfusion, Grade 3 thrombocytopenia associated with clinically significant bleeding, Grade 3 neutropenia associated with infection as described in CTCAE version 4.0, drug related Grade 3 or 4 non-hematologic toxicity, drug related Grade 3 or 4 nonhematologic laboratory abnormality if any of the following also occur: abnormality leads to hospitalization and abnormality persists for >=7 days from the time of AE onset; drug related toxicity leading to prolonged delay (>2 weeks) in initiating Cycle 2. DLTs were collected during first cycle to establish RP2D.

    Measured: 21 days

  4. Part D: Number of Participants With DLT

    An event was considered a DLT if it occurred within the first 21 days of treatment, and met one of following DLT criteria:hematologic toxicity- Grade4 thrombocytopenia persists for >=7 days from the time of AE onset, Grade 4 neutropenia, Grade 4 or Grade 3 febrile neutropenia persists for >=7 days, Grade4 or Grade3 anemia requiring blood transfusion, Grade 3 thrombocytopenia associated with clinically significant bleeding, Grade 3 neutropenia associated with infection as described in CTCAE version 4.0, drug related Grade 3 or 4 non-hematologic toxicity, drug related Grade 3 or 4 nonhematologic laboratory abnormality if any of the following also occur: abnormality leads to hospitalization and abnormality persists for >=7 days from the time of AE onset; drug related toxicity leading to prolonged delay (>2 weeks) in initiating Cycle 2. DLTs were collected during first cycle to establish RP2D.

    Measured: 21 days

  5. Part E: Number of Participants With DLT

    An event was considered a DLT if it occurred within the first 21 days of treatment, and met one of following DLT criteria:hematologic toxicity- Grade4 thrombocytopenia persists for >=7 days from the time of AE onset, Grade 4 neutropenia, Grade 4 or Grade 3 febrile neutropenia persists for >=7 days, Grade4 or Grade3 anemia requiring blood transfusion, Grade 3 thrombocytopenia associated with clinically significant bleeding, Grade 3 neutropenia associated with infection as described in CTCAE version 4.0, drug related Grade 3 or 4 non-hematologic toxicity, drug related Grade 3 or 4 nonhematologic laboratory abnormality if any of the following also occur: abnormality leads to hospitalization and abnormality persists for >=7 days from the time of AE onset; drug related toxicity leading to prolonged delay (>2 weeks) in initiating Cycle 2. DLTs were collected during first cycle to establish RP2D.

    Measured: 21 days

  6. Part F: Number of Participants With DLT

    An event was considered a DLT if it occurred within the first 21 days of treatment, and met one of following DLT criteria:hematologic toxicity- Grade4 thrombocytopenia persists for >=7 days from the time of AE onset, Grade 4 neutropenia, Grade 4 or Grade 3 febrile neutropenia persists for >=7 days, Grade4 or Grade3 anemia requiring blood transfusion, Grade 3 thrombocytopenia associated with clinically significant bleeding, Grade 3 neutropenia associated with infection as described in CTCAE version 4.0, drug related Grade 3 or 4 non-hematologic toxicity, drug related Grade 3 or 4 nonhematologic laboratory abnormality if any of the following also occur: abnormality leads to hospitalization and abnormality persists for >=7 days from the time of AE onset; drug related toxicity leading to prolonged delay (>2 weeks) in initiating Cycle 2. DLTs were collected during first cycle to establish RP2D.

    Measured: 21 days

  7. Part G: Number of Participants With DLT

    An event was considered a DLT if it occurred within the first 21 days of treatment, and met one of following DLT criteria:hematologic toxicity- Grade4 thrombocytopenia persists for >=7 days from the time of AE onset, Grade 4 neutropenia, Grade 4 or Grade 3 febrile neutropenia persists for >=7 days, Grade4 or Grade3 anemia requiring blood transfusion, Grade 3 thrombocytopenia associated with clinically significant bleeding, Grade 3 neutropenia associated with infection as described in CTCAE version 4.0, drug related Grade 3 or 4 non-hematologic toxicity, drug related Grade 3 or 4 nonhematologic laboratory abnormality if any of the following also occur: abnormality leads to hospitalization and abnormality persists for >=7 days from the time of AE onset; drug related toxicity leading to prolonged delay (>2 weeks) in initiating Cycle 2. DLTs were planned to be collected during first cycle to establish RP2D.

    Measured: 21 days

  8. Part H: Number of Participants With DLT

    An event was considered a DLT if it occurred within the first 21 days of treatment, and met one of following DLT criteria:hematologic toxicity- Grade4 thrombocytopenia persists for >=7 days from the time of AE onset, Grade 4 neutropenia, Grade 4 or Grade 3 febrile neutropenia persists for >=7 days, Grade4 or Grade3 anemia requiring blood transfusion, Grade 3 thrombocytopenia associated with clinically significant bleeding, Grade 3 neutropenia associated with infection as described in CTCAE version 4.0, drug related Grade 3 or 4 non-hematologic toxicity, drug related Grade 3 or 4 nonhematologic laboratory abnormality if any of the following also occur: abnormality leads to hospitalization and abnormality persists for >=7 days from the time of AE onset; drug related toxicity leading to prolonged delay (>2 weeks) in initiating Cycle 2. DLTs were planned to be collected during first cycle to establish RP2D.

    Measured: 21 days

  9. Part I: Number of Participants With DLT

    An event was considered a DLT if it occurred within the first 21 days of treatment, and met one of following DLT criteria:hematologic toxicity- Grade4 thrombocytopenia persists for >=7 days from the time of AE onset, Grade 4 neutropenia, Grade 4 or Grade 3 febrile neutropenia persists for >=7 days, Grade4 or Grade3 anemia requiring blood transfusion, Grade 3 thrombocytopenia associated with clinically significant bleeding, Grade 3 neutropenia associated with infection as described in CTCAE version 4.0, drug related Grade 3 or 4 non-hematologic toxicity, drug related Grade 3 or 4 nonhematologic laboratory abnormality if any of the following also occur: abnormality leads to hospitalization and abnormality persists for >=7 days from the time of AE onset; drug related toxicity leading to prolonged delay (>2 weeks) in initiating Cycle 2. DLTs were planned to be collected during first cycle to establish RP2D.

    Measured: 21 days

  10. Part A: Number of Participants With Non-serious Treatment-emergent Adverse Events (TEAEs), Serious TEAEs (STEAEs) and Adverse Events of Special Interest (AESIs)

    An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. An SAE is defined as any untoward medical occurrence that, at any dose; results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or any other situation according to medical or scientific judgement. TEAE is any event that was not present prior to the initiation of study treatment or any event already present that worsens in either intensity or frequency following exposure to study treatment. Number of participants with TEAEs, SAEs and AESIs are reported.

    Measured: Up to 28.5 months

  11. Part B: Number of Participants With Non-serious TEAEs, STEAEs and AESIs

    An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. An SAE is defined as any untoward medical occurrence that, at any dose; results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or any other situation according to medical or scientific judgement. TEAE is any event that was not present prior to the initiation of study treatment or any event already present that worsens in either intensity or frequency following exposure to study treatment. Number of participants with TEAEs, SAEs and AESIs are reported.

    Measured: Up to 28.5 months

  12. Part C: Number of Participants With Non-serious TEAEs, STEAEs and AESIs

    An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. An SAE is defined as any untoward medical occurrence that, at any dose; results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or any other situation according to medical or scientific judgement. TEAE is any event that was not present prior to the initiation of study treatment or any event already present that worsens in either intensity or frequency following exposure to study treatment. Number of participants with TEAEs, SAEs and AESIs are reported.

    Measured: Up to 22.5 months

  13. Part D: Number of Participants With Non-serious TEAEs, STEAEs and AESIs

    An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. An SAE is defined as any untoward medical occurrence that, at any dose; results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or any other situation according to medical or scientific judgement. TEAE is any event that was not present prior to the initiation of study treatment or any event already present that worsens in either intensity or frequency following exposure to study treatment. Number of participants with TEAEs, SAEs and AESIs are reported.

    Measured: Up to 9.5 months

  14. Part E: Number of Participants With Non-serious TEAEs, STEAEs and AESIs

    An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. An SAE is defined as any untoward medical occurrence that, at any dose; results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or any other situation according to medical or scientific judgement. TEAE is any event that was not present prior to the initiation of study treatment or any event already present that worsens in either intensity or frequency following exposure to study treatment. Number of participants with TEAEs, SAEs and AESIs are reported.

    Measured: Up to 4.4 months

  15. Part F: Number of Participants With Non-serious TEAEs, STEAEs and AESIs

    An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. An SAE is defined as any untoward medical occurrence that, at any dose; results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or any other situation according to medical or scientific judgement. TEAE is any event that was not present prior to the initiation of study treatment or any event already present that worsens in either intensity or frequency following exposure to study treatment. Number of participants with TEAEs, SAEs and AESIs are reported.

    Measured: Up to 3.5 months

  16. Part G: Number of Participants With Non-serious TEAEs, STEAEs and AESIs

    An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. An SAE is defined as any untoward medical occurrence that, at any dose; results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or any other situation according to medical or scientific judgement. TEAE is any event that was not present prior to the initiation of study treatment or any event already present that worsens in either intensity or frequency following exposure to study treatment.

    Measured: Up to 24 months

  17. Part H: Number of Participants With Non-serious TEAEs, STEAEs and AESIs

    An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. An SAE is defined as any untoward medical occurrence that, at any dose; results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or any other situation according to medical or scientific judgement. TEAE is any event that was not present prior to the initiation of study treatment or any event already present that worsens in either intensity or frequency following exposure to study treatment.

    Measured: Up to 24 months

  18. Part I: Number of Participants With Non-serious TEAEs, STEAEs and AESIs

    An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. An SAE is defined as any untoward medical occurrence that, at any dose; results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or any other situation according to medical or scientific judgement. TEAE is any event that was not present prior to the initiation of study treatment or any event already present that worsens in either intensity or frequency following exposure to study treatment.

    Measured: Up to 24 months

Secondary outcomes (214)

  1. Part A: Objective Response Rate

    Objective Response Rate is defined as the percentage of participants who achieved confirmed complete response (CR) or partial response (PR), evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 based on Investigator assessment; where CR=Disappearance of all target lesions. Any pathological lymph nodes must be <10 millimeters (mm) in the short axis. PR=At least a 30 percent (%) decrease in the sum of the diameters of target lesions, taking as a reference, the Baseline sum of the diameters.

    Measured: Up to 28.5 months

  2. Part B: Objective Response Rate

    Objective Response Rate is defined as the percentage of participants who achieved confirmed CR or PR, evaluated using RECIST version 1.1 based on Investigator assessment; where CR=Disappearance of all target lesions. Any pathological lymph nodes must be <10 mm in the short axis. PR=At least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the Baseline sum of the diameters.

    Measured: Up to 28.5 months

  3. Part C: Objective Response Rate

    Objective Response Rate is defined as the percentage of participants who achieved confirmed CR or PR, evaluated using RECIST version 1.1 based on Investigator assessment; where CR=Disappearance of all target lesions. Any pathological lymph nodes must be <10 mm in the short axis. PR=At least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the Baseline sum of the diameters.

    Measured: Up to 22.5 months

  4. Part D: Objective Response Rate

    Objective Response Rate is defined as the percentage of participants who achieved confirmed CR or PR, evaluated using RECIST version 1.1 based on Investigator assessment; where CR=Disappearance of all target lesions. Any pathological lymph nodes must be <10 mm in the short axis. PR=At least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the Baseline sum of the diameters.

    Measured: Up to 9.5 months

  5. Part E: Objective Response Rate

    Objective Response Rate is defined as the percentage of participants who achieved confirmed CR or PR, evaluated using RECIST version 1.1 based on Investigator assessment; where CR=Disappearance of all target lesions. Any pathological lymph nodes must be <10 mm in the short axis. PR=At least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the Baseline sum of the diameters.

    Measured: Up to 4.4 months

  6. Part F: Objective Response Rate

    Objective Response Rate is defined as the percentage of participants who achieved confirmed CR or PR, evaluated using RECIST version 1.1 based on Investigator assessment; where CR=Disappearance of all target lesions. Any pathological lymph nodes must be <10 mm in the short axis. PR=At least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the Baseline sum of the diameters.

    Measured: Up to 3.5 months

  7. Part G: Objective Response Rate

    Objective Response Rate is defined as the percentage of participants who achieved confirmed CR or PR, evaluated using RECIST version 1.1 based on Investigator assessment; where CR=Disappearance of all target lesions. Any pathological lymph nodes must be <10 mm in the short axis. PR=At least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the Baseline sum of the diameters.

    Measured: Up to 24 months

  8. Part H: Objective Response Rate

    Objective Response Rate is defined as the percentage of participants who achieved confirmed CR or PR, evaluated using RECIST version 1.1 based on Investigator assessment; where CR=Disappearance of all target lesions. Any pathological lymph nodes must be <10 mm in the short axis. PR=At least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the Baseline sum of the diameters.

    Measured: Up to 24 months

  9. Part I: Objective Response Rate

    Objective Response Rate is defined as the percentage of participants who achieved confirmed CR or PR, evaluated using RECIST version 1.1 based on Investigator assessment; where CR=Disappearance of all target lesions. Any pathological lymph nodes must be <10 mm in the short axis. PR=At least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the Baseline sum of the diameters.

    Measured: Up to 24 months

  10. Part A: Duration of Response

    Duration of response is defined as the time from first documentation of response (CR or PR) until the time of first documentation of disease progression by RECIST version 1.1 or death by any cause.

    Measured: Up to 28.5 months

  11. Part B: Duration of Response

    Duration of response is defined as the time from first documentation of response (CR or PR) until the time of first documentation of disease progression by RECIST version 1.1 or death by any cause.

    Measured: Up to approximately 66 months

  12. Part C: Duration of Response

    Duration of response is defined as the time from first documentation of response (CR or PR) until the time of first documentation of disease progression by RECIST version 1.1 or death by any cause.

    Measured: Up to approximately 60 months

  13. Part D: Duration of Response

    Duration of response is defined as the time from first documentation of response (CR or PR) until the time of first documentation of disease progression by RECIST version 1.1 or death by any cause.

    Measured: Up to approximately 62.5 months

  14. Part E: Duration of Response

    Duration of response is defined as the time from first documentation of response (CR or PR) until the time of first documentation of disease progression by RECIST version 1.1 or death by any cause.

    Measured: Up to 4.4 months

  15. Part F: Duration of Response

    Duration of response is defined as the time from first documentation of response (CR or PR) until the time of first documentation of disease progression by RECIST version 1.1 or death by any cause.

    Measured: Up to 3.5 months

  16. Part G: Duration of Response

    Duration of response is defined as the time from first documentation of response (CR or PR) until the time of first documentation of disease progression by RECIST version 1.1 or death by any cause.

    Measured: Up to 24 months

  17. Part H: Duration of Response

    Duration of response is defined as the time from first documentation of response (CR or PR) until the time of first documentation of disease progression by RECIST version 1.1 or death by any cause.

    Measured: Up to 24 months

  18. Part I: Duration of Response

    Duration of response is defined as the time from first documentation of response (CR or PR) until the time of first documentation of disease progression by RECIST version 1.1 or death by any cause.

    Measured: Up to 24 months

  19. Part A: Disease Control Rate

    Disease Control Rate is defined as the percentage of participants who had achieved CR, PR, or stable disease (SD) per RECIST version 1.1.

    Measured: Up to 28.5 months

  20. Part B: Disease Control Rate

    Disease Control Rate is defined as the percentage of participants who had achieved CR, PR, or SD per RECIST version 1.1.

    Measured: Up to 28.5 months

  21. Part C: Disease Control Rate

    Disease Control Rate is defined as the percentage of participants who had achieved CR, PR, or SD per RECIST version 1.1.

    Measured: Up to 22.5 months

  22. Part D: Disease Control Rate

    Disease Control Rate is defined as the percentage of participants who had achieved CR, PR, or SD per RECIST version 1.1.

    Measured: Up to 9.5 months

  23. Part E: Disease Control Rate

    Disease Control Rate is defined as the percentage of participants who had achieved CR, PR, or SD per RECIST version 1.1.

    Measured: Up to 4.4 months

  24. Part F: Disease Control Rate

    Disease Control Rate is defined as the percentage of participants who had achieved CR, PR, or SD per RECIST version 1.1.

    Measured: Up to 3.5 months

  25. Part G: Disease Control Rate

    Disease Control Rate is defined as the percentage of participants who had achieved CR, PR, or SD per RECIST version 1.1.

    Measured: Up to 24 months

  26. Part H: Disease Control Rate

    Disease Control Rate is defined as the percentage of participants who had achieved CR, PR, or SD per RECIST version 1.1.

    Measured: Up to 24 months

  27. Part I: Disease Control Rate

    Disease Control Rate is defined as the percentage of participants who had achieved CR, PR, or SD per RECIST version 1.1.

    Measured: Up to 24 months

  28. Part A: Progression-free Survival

    Progression-free Survival is defined as the date of first dose to the date of disease progression or death due to any cause, whichever occurs earlier. Progressive Disease (PD) is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study.

    Measured: Up to 28.5 months

  29. Part B: Progression-free Survival

    Progression-free Survival is defined as the date of first dose to the date of disease progression or death due to any cause, whichever occurs earlier. PD is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study.

    Measured: Up to 28.5 months

  30. Part C: Progression-free Survival

    Progression-free Survival is defined as the date of first dose to the date of disease progression or death due to any cause, whichever occurs earlier. PD is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study.

    Measured: Up to 22.5 months

  31. Part D: Progression-free Survival

    Progression-free Survival is defined as the date of first dose to the date of disease progression or death due to any cause, whichever occurs earlier. PD is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study.

    Measured: Up to 9.5 months

  32. Part E: Progression-free Survival

    Progression-free Survival is defined as the date of first dose to the date of disease progression or death due to any cause, whichever occurs earlier. PD is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study.

    Measured: Up to 4.4 months

  33. Part F: Progression-free Survival

    Progression-free Survival is defined as the date of first dose to the date of disease progression or death due to any cause, whichever occurs earlier. PD is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study.

    Measured: Up to 3.5 months

  34. Part G: Progression-free Survival

    Progression-free Survival is defined as the date of first dose to the date of disease progression or death due to any cause, whichever occurs earlier.

    Measured: Up to 24 months

  35. Part H: Progression-free Survival

    Progression-free Survival is defined as the date of first dose to the date of disease progression or death due to any cause, whichever occurs earlier.

    Measured: Up to 24 months

  36. Part I: Progression-free Survival

    Progression-free Survival is defined as the date of first dose to the date of disease progression or death due to any cause, whichever occurs earlier.

    Measured: Up to 24 months

  37. Part A: Number of Participants With Positive Anti-TSR-042 Antibodies

    Serum samples were collected at indicated time points and tested for the presence of antibodies that bind to TSR-042. The presence of anti-TSR-042 antibodies were assessed using a tiered approach using electrochemiluminescence (that is, screening, confirmation, titer, and neutralizing antibody assay). Anti-drug Antibody Population consisted of all participants who received at least 1 dose of study treatment and had provided a pre-dose blood sample and at least 1 post-dose blood sample at or after 96 hours.

    Measured: Up to 28.5 months

  38. Part B: Number of Participants With Positive Anti-TSR-042 Antibodies

    Serum samples were collected at indicated time points and tested for the presence of antibodies that bind to TSR-042. The presence of anti-TSR-042 antibodies were assessed using a tiered approach using electrochemiluminescence (that is, screening, confirmation, titer, and neutralizing antibody assay).

    Measured: Up to 28.5 months

  39. Part C: Number of Participants With Positive Anti-TSR-042 Antibodies

    Serum samples were collected at indicated time points and tested for the presence of antibodies that bind to TSR-042. The presence of anti-TSR-042 antibodies were assessed using a tiered approach using electrochemiluminescence (that is, screening, confirmation, titer, and neutralizing antibody assay).

    Measured: Up to 22.5 months

  40. Part D: Number of Participants With Positive Anti-TSR-042 Antibodies

    Serum samples were collected at indicated time points and tested for the presence of antibodies that bind to TSR-042. The presence of anti-TSR-042 antibodies were assessed using a tiered approach using electrochemiluminescence (that is, screening, confirmation, titer, and neutralizing antibody assay).

    Measured: Up to 9.5 months

  41. Part E: Number of Participants With Positive Anti-TSR-042 Antibodies

    Serum samples were collected at indicated time points and tested for the presence of antibodies that bind to TSR-042. The presence of anti-TSR-042 antibodies were assessed using a tiered approach using electrochemiluminescence (that is, screening, confirmation, titer, and neutralizing antibody assay).

    Measured: Up to 4.4 months

  42. Part F: Number of Participants With Positive Anti-TSR-042 Antibodies

    Serum samples were collected at indicated time points and tested for the presence of antibodies that bind to TSR-042. The presence of anti-TSR-042 antibodies were assessed using a tiered approach using electrochemiluminescence (that is, screening, confirmation, titer, and neutralizing antibody assay).

    Measured: Up to 3.5 months

  43. Part F: Number of Participants With Positive Anti-TSR-022 Antibodies

    Serum samples were collected at indicated time points and tested for the presence of antibodies that bind to TSR-022. The presence of anti-TSR-022 antibodies were assessed using a tiered approach using electrochemiluminescence (that is, screening, confirmation, titer, and neutralizing antibody assay).

    Measured: Up to 3.5 months

  44. Part G: Number of Participants With Positive Anti-TSR-042 Antibodies

    Serum samples were planned to be collected at indicated time points and tested for the presence of antibodies that bind to TSR-042. The presence of anti-TSR-042 antibodies were planeed to be assessed using a tiered approach using electrochemiluminescence (that is, screening, confirmation, titer, and neutralizing antibody assay).

    Measured: Up to 24 months

  45. Part H: Number of Participants With Positive Anti-TSR-042 Antibodies

    Serum samples were planned to be collected at indicated time points and tested for the presence of antibodies that bind to TSR-042. The presence of anti-TSR-042 antibodies were planned to be assessed using a tiered approach using electrochemiluminescence (that is, screening, confirmation, titer, and neutralizing antibody assay).

    Measured: Up to 24 months

  46. Part H: Number of Participants With Positive Anti-TSR-022 Antibodies

    Serum samples were planned to be collected at indicated time points and tested for the presence of antibodies that bind to TSR-022. The presence of anti-TSR-022 antibodies were planned to be assessed using a tiered approach using electrochemiluminescence (that is, screening, confirmation, titer, and neutralizing antibody assay).

    Measured: Up to 24 months

  47. Part I: Number of Participants With Positive Anti-TSR-042 Antibodies

    Serum samples were planned to be collected at indicated time points and tested for the presence of antibodies that bind to TSR-042. The presence of anti-TSR-042 antibodies were planned to be assessed using a tiered approach using electrochemiluminescence (that is, screening, confirmation, titer, and neutralizing antibody assay).

    Measured: Up to 24 months

  48. Part I: Number of Participants With Positive Anti-TSR-022 Antibodies

    Serum samples were planned to be collected at indicated time points and tested for the presence of antibodies that bind to TSR-022. The presence of anti-TSR-022 antibodies were planned to be assessed using a tiered approach using electrochemiluminescence (that is, screening, confirmation, titer, and neutralizing antibody assay).

    Measured: Up to 24 months

  49. Part A: Area Under the Plasma Concentration From Time Zero to t (AUC[0-t]) of Niraparib

    Blood samples were collected at indicated time points. Pharmacokinetic (PK) parameters of niraparib were calculated using non-compartmental methods. PK population consisted of all participants who received at least 1 dose of study treatment and had at least 1 PK sample.

    Measured: Cycles 1 and 2: Pre-dose, 1, 2, 4, 6, 8 and 24 hours post-dose (each cycle was 21 days)

  50. Part A: AUC(0-t) of TSR-042

    Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.

    Measured: Cycles 1 and 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days)

  51. Part B: AUC0-t of TSR-042

    Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.

    Measured: Cycles 1 and 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days)

  52. Part C: AUC0-t of Niraparib

    Blood samples were collected at indicated time points. PK parameters of niraparib were calculated using non-compartmental methods.

    Measured: Cycles 1 and 2: Pre-dose, 1, 2, 4, 6, 8 and 24 hours post-dose (each cycle was 21 days)

  53. Part C: AUC0-t of TSR-042

    Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.

    Measured: Cycles 1 and 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days)

  54. Part D: AUC0-t of TSR-042

    Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.

    Measured: Cycles 1 and 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days)

  55. Part E: AUC0-t of TSR-042

    Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.

    Measured: Cycle 1: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose; Cycle 2: Pre-dose (each cycle was 21 days)

  56. Part F: AUC0-t of TSR-042

    Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.

    Measured: Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168 and 336 hours post-dose; Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)

  57. Part F: AUC0-t of TSR-022

    Blood samples were collected at indicated time points. PK parameters of TSR-022 were calculated using non-compartmental methods.

    Measured: Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168 and 336 hours post-dose; Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)

  58. Part G: AUC0-t of TSR-042

    Blood samples were planned to be collected at indicated time points.

    Measured: Cycles 1 and 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose; Cycle 2: Pre-dose (each cycle was 21 days)

  59. Part H: AUC0-t of TSR-042

    Blood samples were planned to be collected at indicated time points.

    Measured: Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168 and 336 hours post-dose; Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)

  60. Part H: AUC0-t of TSR-022

    Blood samples were planned to be collected at indicated time points.

    Measured: Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168 and 336 hours post-dose; Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)

  61. Part I: AUC0-t of TSR-042

    Blood samples were planned to be collected at indicated time points.

    Measured: Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168 and 336 hours post-dose; Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)

  62. Part I: AUC0-t of TSR-022

    Blood samples were planned to be collected at indicated time points.

    Measured: Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168 and 336 hours post-dose; Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)

  63. Part A: Area Under the Plasma Concentration From Time Zero to Infinity (AUC[0-infinity]) of Niraparib

    Blood samples were collected at indicated time points. PK parameters of niraparib were calculated using non-compartmental methods.

    Measured: Cycles 1 and 2: Pre-dose, 1, 2, 4, 6, 8 and 24 hours post-dose (each cycle was 21 days)

  64. Part A: AUC(0-infinity) of TSR-042

    Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.

    Measured: Cycles 1 and 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days)

  65. Part B: AUC(0-infinity) of TSR-042

    Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.

    Measured: Cycles 1 and 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days)

  66. Part C: AUC(0-infinity) of Niraparib

    Blood samples were collected at indicated time points. PK parameters of niraparib were calculated using non-compartmental methods.

    Measured: Cycles 1 and 2: Pre-dose, 1, 2, 4, 6, 8 and 24 hours post-dose (each cycle was 21 days)

  67. Part C: AUC(0-infinity) of TSR-042

    Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.

    Measured: Cycles 1 and 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days)

  68. Part D: AUC(0-infinity) of TSR-042

    Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.

    Measured: Cycles 1 and 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days)

  69. Part E: AUC(0-infinity) of TSR-042

    Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.

    Measured: Cycle 1: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose; Cycle 2: Pre-dose (each cycle was 21 days)

  70. Part F: AUC(0-infinity) of TSR-042

    Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.

    Measured: Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168, and 336 hours post-dose; Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)

  71. Part F: AUC(0-infinity) of TSR-022

    Blood samples were collected at indicated time points. PK parameters of TSR-022 were calculated using non-compartmental methods.

    Measured: Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168 and 336 hours post-dose; Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168 and 336 hours post-dose (each cycle was 21 days)

  72. Part G: AUC(0-infinity) of TSR-042

    Blood samples were planned to be collected at indicated time points.

    Measured: Cycles 1 and 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose; Cycle 2: Pre-dose (each cycle was 21 days)

  73. Part H: AUC(0-infinity) of TSR-042

    Blood samples were planned to be collected at indicated time points.

    Measured: Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168 and 336 hours post-dose; Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 96, 168, and 336 hours post-dose (each cycle was 21 days)

  74. Part H: AUC(0-infinity) of TSR-022

    Blood samples were planned to be collected at indicated time points.

    Measured: Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168 and 336 hours post-dose; Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 96, 168, and 336 hours post-dose (each cycle was 21 days)

  75. Part I: AUC(0-infinity) of TSR-042

    Blood samples were planned to be collected at indicated time points.

    Measured: Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168 and 336 hours post-dose; Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)

  76. Part I: AUC(0-infinity) of TSR-022

    Blood samples were planned to be collected at indicated time points.

    Measured: Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168 and 336 hours post-dose; Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)

  77. Part A: Observed Concentration at the End of the Dosing Interval (Ctau) of Niraparib

    Blood samples were collected at indicated time points. PK parameters of niraparib were calculated using non-compartmental methods.

    Measured: Cycle 1: Pre-dose, 1, 2, 4, 6, 8 and 24 hours post-dose (each cycle was 21 days)

  78. Part A: Ctau of TSR-042

    Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.

    Measured: Cycle 1: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose (each cycle was 21 days)

  79. Part B: Ctau of TSR-042

    Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.

    Measured: Cycle 1: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose (each cycle was 21 days)

  80. Part C: Ctau of Niraparib

    Blood samples were collected at indicated time points. PK parameters of niraparib were calculated using non-compartmental methods.

    Measured: Cycle 1: Pre-dose, 1, 2, 4, 6, 8 and 24 hours post-dose (each cycle was 21 days)

  81. Part C: Ctau of TSR-042

    Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.

    Measured: Cycle 1: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose (each cycle was 21 days)

  82. Part D: Ctau of TSR-042

    Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.

    Measured: Cycle 1: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose (each cycle was 21 days)

  83. Part E: Ctau of TSR-042

    Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.

    Measured: Cycle 1: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)

  84. Part F: Ctau of TSR-042

    Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.

    Measured: Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)

  85. Part F: Ctau of TSR-022

    Blood samples were collected at indicated time points. PK parameters of TSR-022 were calculated using non-compartmental methods.

    Measured: Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)

  86. Part G: Ctau of TSR-042

    Blood samples were planned to be collected at indicated time points.

    Measured: Cycle 1: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)

  87. Part H: Ctau of TSR-042

    Blood samples were planned to be collected at indicated time points.

    Measured: Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168 and 336 hours post-dose (each cycle was 21 days)

  88. Part H: Ctau of TSR-022

    Blood samples were planned to be collected at indicated time points.

    Measured: Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168 and 336 hours post-dose (each cycle was 21 days)

  89. Part I: Ctau of TSR-042

    Blood samples were planned to be collected at indicated time points.

    Measured: Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168 and 336 hours post-dose (each cycle was 21 days)

  90. Part I: Ctau of TSR-022

    Blood samples were planned to be collected at indicated time points.

    Measured: Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168 and 336 hours post-dose (each cycle was 21 days)

  91. Part A: Maximum Observed Plasma (Cmax) of Niraparib

    Blood samples were collected at indicated time points. PK parameters of niraparib were calculated using non-compartmental methods.

    Measured: Cycle 1: Pre-dose, 1, 2, 4, 6, 8 and 24 hours post-dose (each cycle was 21 days)

  92. Part A: Cmax of TSR-042

    Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.

    Measured: Cycle 1: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose (each cycle was 21 days)

  93. Part B: Cmax of TSR-042

    Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.

    Measured: Cycle 1: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose (each cycle was 21 days)

  94. Part C: Cmax of Niraparib

    Blood samples were collected at indicated time points. PK parameters of niraparib were calculated using non-compartmental methods.

    Measured: Cycle 1: Pre-dose, 1, 2, 4, 6, 8 and 24 hours post-dose (each cycle was 21 days)

  95. Part C: Cmax of TSR-042

    Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.

    Measured: Cycle 1: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose (each cycle was 21 days)

  96. Part D: Cmax of TSR-042

    Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.

    Measured: Cycle 1: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose (each cycle was 21 days)

  97. Part E: Cmax of TSR-042

    Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.

    Measured: Cycle 1: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)

  98. Part F: Cmax of TSR-042

    Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.

    Measured: Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)

  99. Part F: Cmax of TSR-022

    Blood samples were collected at indicated time points. PK parameters of TSR-022 were calculated using non-compartmental methods.

    Measured: Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168 and 336 hours post-dose (each cycle was 21 days)

  100. Part G: Cmax of TSR-042

    Blood samples were planned to be collected at indicated time points.

    Measured: Cycle 1: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)

  101. Part H: Cmax of TSR-042

    Blood samples were planned to be collected at indicated time points.

    Measured: Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168 and 336 hours post-dose (each cycle was 21 days)

  102. Part H: Cmax of TSR-022

    Blood samples were planned to be collected at indicated time points.

    Measured: Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168 and 336 hours post-dose (each cycle was 21 days)

  103. Part I: Cmax of TSR-042

    Blood samples were planned to be collected at indicated time points.

    Measured: Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168 and 336 hours post-dose (each cycle was 21 days)

  104. Part I: Cmax of TSR-022

    Blood samples were planned to be collected at indicated time points.

    Measured: Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168 and 336 hours post-dose (each cycle was 21 days)

  105. Part A: Clearance After Oral Administration (CL/F) of Niraparib

    Blood samples were collected at indicated time points. PK parameters of niraparib were calculated using non-compartmental methods.

    Measured: Cycles 1 and 2: Pre-dose, 1, 2, 4, 6, 8 and 24 hours post-dose (each cycle was 21 days)

  106. Part A: Clearance After Intravenous Administration (CL) of TSR-042

    Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.

    Measured: Cycles 1 and 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days)

  107. Part B: CL of TSR-042

    Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.

    Measured: Cycles 1 and 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days)

  108. Part C: CL/F of Niraparib

    Blood samples were collected at indicated time points. PK parameters of niraparib were calculated using non-compartmental methods.

    Measured: Cycles 1 and 2: Pre-dose, 1, 2, 4, 6, 8 and 24 hours post-dose (each cycle was 21 days)

  109. Part C: CL of TSR-042

    Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.

    Measured: Cycles 1 and 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days)

  110. Part D: CL of TSR-042

    Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.

    Measured: Cycles 1 and 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days)

  111. Part E: CL of TSR-042

    Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.

    Measured: Cycle 1: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose; Cycle 2: Pre-dose (each cycle was 21 days)

  112. Part F: CL of TSR-042

    Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.

    Measured: Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168, and 336 hours post-dose; Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)

  113. Part F: CL of TSR-022

    Blood samples were collected at indicated time points. PK parameters of TSR-022 were calculated using non-compartmental methods.

    Measured: Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168, and 336 hours post-dose; Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)

  114. Part G: CL of TSR-042

    Blood samples were planned to be collected at indicated time points.

    Measured: Cycles 1 and 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose; Cycle 2: Pre-dose (each cycle was 21 days)

  115. Part H: CL of TSR-042

    Blood samples were planned to be collected at indicated time points.

    Measured: Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168 and 336 hours post-dose; Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 96, 168, and 336 hours post-dose (each cycle was 21 days)

  116. Part H: CL of TSR-022

    Blood samples were planned to be collected at indicated time points.

    Measured: Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168 and 336 hours post-dose; Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 96, 168, and 336 hours post-dose (each cycle was 21 days)

  117. Part I: CL of TSR-042

    Blood samples were planned to be collected at indicated time points.

    Measured: Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168 and 336 hours post-dose; Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)

  118. Part I: CL of TSR-022

    Blood samples were planned to be collected at indicated time points.

    Measured: Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168 and 336 hours post-dose; Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)

  119. Part A: Volume of Distribution After Oral Administration (Vz/F) of Niraparib

    Blood samples were collected at indicated time points. PK parameters of niraparib were calculated using non-compartmental methods.

    Measured: Cycles 1 and 2: Pre-dose, 1, 2, 4, 6, 8 and 24 hours post-dose (each cycle was 21 days)

  120. Part A: Volume of Distribution After Intravenous Administration (Vz) of of TSR-042

    Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.

    Measured: Cycles 1 and 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days)

  121. Part B: Vz of TSR-042

    Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.

    Measured: Cycles 1 and 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days)

  122. Part C: Vz/F of Niraparib

    Blood samples were collected at indicated time points. PK parameters of niraparib were calculated using non-compartmental methods.

    Measured: Cycles 1 and 2: Pre-dose, 1, 2, 4, 6, 8 and 24 hours post-dose (each cycle was 21 days)

  123. Part C: Vz of TSR-042

    Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.

    Measured: Cycles 1 and 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days)

  124. Part D: Vz of TSR-042

    Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.

    Measured: Cycles 1 and 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days)

  125. Part E: Vz of TSR-042

    Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.

    Measured: Cycle 1: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose; Cycle 2: Pre-dose (each cycle was 21 days)

  126. Part F: Vz of TSR-042

    Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.

    Measured: Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168, and 336 hours post-dose; Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)

  127. Part F: Vz of TSR-022

    Blood samples were collected at indicated time points. PK parameters of TSR-022 were calculated using non-compartmental methods.

    Measured: Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168, and 336 hours post-dose; Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)

  128. Part G: Vz of TSR-042

    Blood samples were planned to be collected at indicated time points.

    Measured: Cycles 1 and 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose; Cycle 2: Pre-dose (each cycle was 21 days)

  129. Part H: Vz of TSR-042

    Blood samples were planned to be collected at indicated time points.

    Measured: Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168 and 336 hours post-dose; Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 96, 168, and 336 hours post-dose (each cycle was 21 days)

  130. Part H: Vz of TSR-022

    Blood samples were planned to be collected at indicated time points.

    Measured: Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168 and 336 hours post-dose; Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 96, 168, and 336 hours post-dose (each cycle was 21 days)

  131. Part I: Vz of TSR-042

    Blood samples were planned to be collected at indicated time points.

    Measured: Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168 and 336 hours post-dose; Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)

  132. Part I: Vz of TSR-022

    Blood samples were planned to be collected at indicated time points.

    Measured: Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168 and 336 hours post-dose; Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)

  133. Part A: AUC at Steady State (AUCss) of Niraparib

    Blood samples were collected at indicated time points. PK parameters of niraparib were calculated using non-compartmental methods.

    Measured: Cycle 2: Pre-dose, 1, 2, 4, 6, 8 and 24 hours post-dose (each cycle was 21 days)

  134. Part A: AUCss of TSR-042

    Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.

    Measured: Cycle 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days)

  135. Part B: AUCss of TSR-042

    Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.

    Measured: Cycle 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days)

  136. Part C: AUCss of Niraparib

    Blood samples were collected at indicated time points. PK parameters of niraparib were calculated using non-compartmental methods.

    Measured: Cycle 2: Pre-dose, 1, 2, 4, 6, 8 and 24 hours post-dose (each cycle was 21 days)

  137. Part C: AUCss of TSR-042

    Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.

    Measured: Cycle 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days)

  138. Part D: AUCss of TSR-042

    Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.

    Measured: Cycle 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days)

  139. Part E: AUCss of TSR-042

    Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.

    Measured: Cycle 2: Pre-dose (each cycle was 21 days)

  140. Part F: AUCss of TSR-042

    Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.

    Measured: Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)

  141. Part F: AUCss of TSR-022

    Blood samples were collected at indicated time points. PK parameters of TSR-022 were calculated using non-compartmental methods.

    Measured: Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)

  142. Part G: AUCss of TSR-042

    Blood samples were planned to be collected at indicated time points.

    Measured: Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)

  143. Part H: AUCss of TSR-042

    Blood samples were planned to be collected at indicated time points.

    Measured: Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 96, 168, and 336 hours post-dose (each cycle was 21 days)

  144. Part H: AUCss of TSR-022

    Blood samples were planned to be collected at indicated time points.

    Measured: Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 96, 168, and 336 hours post-dose (each cycle was 21 days)

  145. Part I: AUCss of TSR-042

    Blood samples were planned to be collected at indicated time points.

    Measured: Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)

  146. Part I: AUCss of TSR-022

    Blood samples were planned to be collected at indicated time points.

    Measured: Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)

  147. Part A: Ctau at Steady State (Ctau,ss) of Niraparib

    Blood samples were collected at indicated time points. PK parameters of niraparib were calculated using non-compartmental methods.

    Measured: Cycle 2: Pre-dose, 1, 2, 4, 6, 8 and 24 hours post-dose; Cycles 5 and 11: Pre-dose, 2 hours post-dose (each cycle was 21 days)

  148. Part A: Ctau,ss of TSR-042

    Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.

    Measured: Cycle 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days)

  149. Part B: Ctau,ss of TSR-042

    Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.

    Measured: Cycle 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days)

  150. Part C: Ctau,ss of Niraparib

    Blood samples were collected at indicated time points. PK parameters of niraparib were calculated using non-compartmental methods.

    Measured: Cycle 2: Pre-dose, 1, 2, 4, 6, 8 and 24 hours post-dose; Cycles 5 and 11: Pre-dose, 2 hours post-dose (each cycle was 21 days)

  151. Part C: Ctau,ss of TSR-042

    Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.

    Measured: Cycle 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days)

  152. Part D: Ctau,ss of TSR-042

    Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.

    Measured: Cycle 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days)

  153. Part E: Ctau,ss of TSR-042

    Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.

    Measured: Cycle 2: Pre-dose (each cycle was 21 days)

  154. Part F: Ctau,ss of TSR-042

    Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.

    Measured: Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)

  155. Part F: Ctau,ss of TSR-022

    Blood samples were collected at indicated time points. PK parameters of TSR-022 were calculated using non-compartmental methods.

    Measured: Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)

  156. Part G: Ctau,ss of TSR-042

    Blood samples were planned to be collected at indicated time points.

    Measured: Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)

  157. Part H: Ctau,ss of TSR-042

    Blood samples were planned to be collected at indicated time points.

    Measured: Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 96, 168, and 336 hours post-dose (each cycle was 21 days)

  158. Part H: Ctau,ss of TSR-022

    Blood samples were planned to be collected at indicated time points.

    Measured: Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 96, 168, and 336 hours post-dose (each cycle was 21 days)

  159. Part I: Ctau,ss of TSR-042

    Blood samples were planned to be collected at indicated time points.

    Measured: Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)

  160. Part I: Ctau,ss of TSR-022

    Blood samples were planned to be collected at indicated time points.

    Measured: Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)

  161. Part A: Cmax at Steady State (Cmax,ss) of Niraparib

    Blood samples were collected at indicated time points. PK parameters of niraparib were calculated using non-compartmental methods.

    Measured: Cycle 2: Pre-dose, 1, 2, 4, 6, 8 and 24 hours post-dose; Cycles 5 and 11: Pre-dose, 2 hours post-dose (each cycle was 21 days)

  162. Part A: Cmax,ss of TSR-042

    Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.

    Measured: Cycle 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days)

  163. Part B: Cmax,ss of TSR-042

    Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.

    Measured: Cycle 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days)

  164. Part C: Cmax,ss of Niraparib

    Blood samples were collected at indicated time points. PK parameters of niraparib were calculated using non-compartmental methods.

    Measured: Cycle 2: Pre-dose, 1, 2, 4, 6, 8 and 24 hours post-dose; Cycles 5 and 11: Pre-dose, 2 hours post-dose (each cycle was 21 days)

  165. Part C: Cmax,ss of TSR-042

    Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.

    Measured: Cycle 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days)

  166. Part D: Cmax,ss of TSR-042

    Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.

    Measured: Cycle 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days)

  167. Part E: Cmax,ss of TSR-042

    Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.

    Measured: Cycle 2: Pre-dose (each cycle was 21 days)

  168. Part F: Cmax,ss of TSR-042

    Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.

    Measured: Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)

  169. Part F: Cmax,ss of TSR-022

    Blood samples were collected at indicated time points. PK parameters of TSR-022 were calculated using non-compartmental methods.

    Measured: Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)

  170. Part G: Cmax,ss of TSR-042

    Blood samples were planned to be collected at indicated time points.

    Measured: Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)

  171. Part H: Cmax,ss of TSR-042

    Blood samples were planned to be collected at indicated time points.

    Measured: Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 96, 168, and 336 hours post-dose (each cycle was 21 days)

  172. Part H: Cmax,ss of TSR-022

    Blood samples were planned to be collected at indicated time points.

    Measured: Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 96, 168, and 336 hours post-dose (each cycle was 21 days)

  173. Part I: Cmax,ss of TSR-042

    Blood samples were planned to be collected at indicated time points.

    Measured: Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)

  174. Part I: Cmax,ss of TSR-022

    Blood samples were planned to be collected at indicated time points.

    Measured: Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)

  175. Part A: Time to Reach Maximum Plasma Concentration (Tmax) of Niraparib

    Blood samples were collected at indicated time points. PK parameters of niraparib were calculated using non-compartmental methods.

    Measured: Cycle 1: Pre-dose, 1, 2, 4, 6, 8 and 24 hours post-dose (each cycle was 21 days)

  176. Part A: Tmax of TSR-042

    Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.

    Measured: Cycle 1: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose (each cycle was 21 days)

  177. Part B: Tmax of TSR-042

    Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.

    Measured: Cycle 1: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose (each cycle was 21 days)

  178. Part C: Tmax of Niraparib

    Blood samples were collected at indicated time points. PK parameters of niraparib were calculated using non-compartmental methods.

    Measured: Cycle 1: Pre-dose, 1, 2, 4, 6, 8 and 24 hours post-dose (each cycle was 21 days)

  179. Part C: Tmax of TSR-042

    Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.

    Measured: Cycle 1: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose (each cycle was 21 days)

  180. Part D: Tmax of TSR-042

    Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.

    Measured: Cycle 1: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose (each cycle was 21 days)

  181. Part E: Tmax of TSR-042

    Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.

    Measured: Cycle 1: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)

  182. Part F: Tmax of TSR-042

    Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.

    Measured: Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)

  183. Part F: Tmax of TSR-022

    Blood samples were collected at indicated time points. PK parameters of TSR-022 were calculated using non-compartmental methods.

    Measured: Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)

  184. Part G: Tmax of TSR-042

    Blood samples were planned to be collected at indicated time points.

    Measured: Cycle 1: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)

  185. Part H: Tmax of TSR-042

    Blood samples were planned to be collected at indicated time points.

    Measured: Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168 and 336 hours post-dose (each cycle was 21 days)

  186. Part H: Tmax of TSR-022

    Blood samples were planned to be collected at indicated time points.

    Measured: Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168 and 336 hours post-dose (each cycle was 21 days)

  187. Part I: Tmax of TSR-042

    Blood samples were planned to be collected at indicated time points.

    Measured: Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168 and 336 hours post-dose (each cycle was 21 days)

  188. Part I: Tmax of TSR-022

    Blood samples were planned to be collected at indicated time points.

    Measured: Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168 and 336 hours post-dose (each cycle was 21 days)

  189. Part A: Tmax at Steady State (Tmax,ss) of Niraparib

    Blood samples were collected at indicated time points. PK parameters of niraparib were calculated using non-compartmental methods.

    Measured: Cycle 2: Pre-dose, 1, 2, 4, 6, 8 and 24 hours post-dose; Cycles 5 and 11: Pre-dose, 2 hours post-dose (each cycle was 21 days)

  190. Part A: Tmax,ss of TSR-042

    Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.

    Measured: Cycle 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days)

  191. Part B: Tmax,ss of TSR-042

    Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.

    Measured: Cycle 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days)

  192. Part C: Tmax,ss of Niraparib

    Blood samples were collected at indicated time points. PK parameters of niraparib were calculated using non-compartmental methods.

    Measured: Cycle 2: Pre-dose, 1, 2, 4, 6, 8 and 24 hours post-dose; Cycles 5 and 11: Pre-dose, 2 hours post-dose (each cycle was 21 days)

  193. Part C: Tmax,ss of TSR-042

    Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.

    Measured: Cycle 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days)

  194. Part D: Tmax,ss of TSR-042

    Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.

    Measured: Cycle 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days)

  195. Part E: Tmax,ss of TSR-042

    Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.

    Measured: Cycle 2: Pre-dose (each cycle was 21 days)

  196. Part F: Tmax,ss of TSR-042

    Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.

    Measured: Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)

  197. Part F: Tmax,ss of TSR-022

    Blood samples were collected at indicated time points. PK parameters of TSR-022 were calculated using non-compartmental methods.

    Measured: Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)

  198. Part G: Tmax,ss of TSR-042

    Blood samples were planned to be collected at indicated time points.

    Measured: Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)

  199. Part H: Tmax,ss of TSR-042

    Blood samples were planned to be collected at indicated time points.

    Measured: Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 96, 168, and 336 hours post-dose (each cycle was 21 days)

  200. Part H: Tmax,ss of TSR-022

    Blood samples were planned to be collected at indicated time points.

    Measured: Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 96, 168, and 336 hours post-dose (each cycle was 21 days)

  201. Part I: Tmax,ss of TSR-042

    Blood samples were planned to be collected at indicated time points.

    Measured: Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)

  202. Part I: Tmax,ss of TSR-022

    Blood samples were planned to be collected at indicated time points.

    Measured: Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)

  203. Part A: Volume of Distribution After Intravenous Administration (Vss) of of TSR-042

    Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.

    Measured: Cycle 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days)

  204. Part B: Vss of TSR-042

    Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.

    Measured: Cycle 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days)

  205. Part C: Vss of TSR-042

    Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.

    Measured: Cycle 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days)

  206. Part D: Vss of TSR-042

    Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.

    Measured: Cycle 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days)

  207. Part E: Vss of TSR-042

    Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.

    Measured: Cycle 2: Pre-dose (each cycle was 21 days)

  208. Part F: Vss of TSR-042

    Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.

    Measured: Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)

  209. Part F: Vss of TSR-022

    Blood samples were collected at indicated time points. PK parameters of TSR-022 were calculated using non-compartmental methods.

    Measured: Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)

  210. Part G: Vss of TSR-042

    Blood samples were planned to be collected at indicated time points.

    Measured: Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)

  211. Part H: Vss of TSR-042

    Blood samples were planned to be collected at indicated time points.

    Measured: Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 96, 168, and 336 hours post-dose (each cycle was 21 days)

  212. Part H: Vss of TSR-022

    Blood samples were planned to be collected at indicated time points.

    Measured: Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 96, 168, and 336 hours post-dose (each cycle was 21 days)

  213. Part I: Vss of TSR-042

    Blood samples were planned to be collected at indicated time points.

    Measured: Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)

  214. Part I: Vss of TSR-022

    Blood samples were planned to be collected at indicated time points.

    Measured: Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 Oct 2017
  2. Study start12 Oct 2017
  3. Primary completion26 Feb 2020
  4. Study completion11 Dec 2024

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
60 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03307785
Sponsor's protocol ID
213351
Other IDs
3000-01-002
Status last verified
Nov 2025
First submitted
26 Sep 2017
Last updated
25 Nov 2025
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Yap TA, Bessudo A, Hamilton E, Sachdev J, Patel MR, Rodon J, Evilevitch L, Duncan M, Guo W, Kumar S, Lu S, Dezube BJ, Gabrail N. IOLite: phase 1b trial of doublet/triplet combinations of dostarlimab with niraparib, carboplatin-paclitaxel, with or without bevacizumab in patients with advanced cancer. J Immunother Cancer. 2022 Mar;10(3):e003924. doi: 10.1136/jitc-2021-003924.

    PubMed 35332062

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Niraparib, TSR-042 and Carboplatin-Paclitaxel in people with Neoplasms and Metastatic Cancer, run by Tesaro, Inc. at 8 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 45 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 25 Nov 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 8 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 10 May 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Part A: Number of Participants With Dose-limiting Toxicity (DLT) (time frame: 21 days). The study lists 18 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03307785, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Nov 2025; AzTrials last refreshed its copy on 6 Nov 2026.

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