AzTrials
AzTrials

Ovarian NeoplasmsPhase 2NCT02674061

Efficacy and Safety Study of Pembrolizumab (MK-3475) in Participants With Advanced Recurrent Ovarian Cancer (MK-3475-100/KEYNOTE-100)

A Phase 2 study testing Pembrolizumab in people with Ovarian Neoplasms, run by Merck Sharp & Dohme LLC.

Completed

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

Official record
Search all trials

Trial summary

This study will assess the efficacy and safety of pembrolizumab (MK-3475) monotherapy in female participants with recurrent ovarian cancer (ROC) who have received up to 5 prior lines of treatment including platinum-based treatment for ROC (1 to 6 total prior lines counting front line therapy). Read more about this study

Who is it for?
Ages 18 years and older, women only
Conditions the study is for
Ovarian Neoplasms
What is being tested?
Pembrolizumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
376 participants
Where
No sites listed yet
Study dates
25 Feb 2016to 18 Mar 2021
Phase
Phase 2
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
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Has histologically confirmed epithelial ovarian cancer, fallopian tube cancer or primary peritoneal cancer
  • Has received a front line platinum-based regimen (administered via either intravenous or intraperitoneal route) per local standard of care or treatment guideline following the primary or interval debulking surgery with documented disease recurrence (note: Maintenance treatment following the front line treatment is permitted and counted together as part of the front line treatment)
  • Has fulfilled the following additional requirements regarding prior treatments for ROC depending on the cohort participant is to be enrolled. Each participant must have documented evidence of clinical response or disease stabilization to the last regimen received.
  • Cohort A: Has received 0 to 2 additional prior lines for treating ROC (or 1-3 total prior lines counting the front line) and must have a platinum-free interval (PFI) of ≥ 3 to 12 months if the last regimen received is a platinum-based, or a treatment-free interval (TFI) of ≥ 3 to 12 months if the last regimen received is a non-platinum-based
  • Cohort B: Has received 3 to 5 additional prior lines for treating ROC (or 4-6 total prior lines counting the front line) and must have a PFI of ≥ 3 months if the last regimen received is a platinum-based, or a TFI of ≥ 3 months if the last regimen received is a non-platinum-based
  • Has measurable disease at baseline based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as determined by the central imaging vendor
Show all 11Show fewer
  • Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  • Has a life expectancy of ≥16 weeks
  • Has provided a tumor tissue sample either collected from prior cytoreductive surgery or fresh newly obtained tumor tissue at screening
  • Has adequate organ function
  • Female participants of childbearing potential must be willing to use an adequate method of contraception for the course of the study through 120 days after the last dose of study drug

Who cannot join

  • Is currently participating in or has participated in a clinical study and received an investigational agent or used an investigational device within 4 weeks prior to the first dose of study treatment
  • Has an active autoimmune disease that has required systemic treatment in the past 2 years (i.e., use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment
  • Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the planned first dose of the study
  • Has had prior anti-cancer monoclonal antibody (mAb), chemotherapy, targeted small molecule therapy, or radiation therapy within 4 weeks prior to the planned first dose of the study
  • Has not recovered from AEs to ≤ Grade 1 or prior treatment level due to a previously administered agent
  • Has epithelial ovarian cancer (EOC) with mucinous histology subtype
Show all 17Show fewer
  • Has a known additional malignancy that progressed or required active treatment within the last 5 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.
  • Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they have stable brain metastases
  • Has known history of, or any evidence of active, non-infectious pneumonitis
  • Has an active infection requiring systemic therapy
  • Has symptoms of bowel obstruction in the past 3 months
  • Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study
  • Is pregnant or breastfeeding, or expecting to conceive children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of study drug
  • Has received prior therapy with an anti-programmed cell death (PD)-1, anti-PD-L1, anti-PD-L2 agent or with an agent directed to another co-inhibitory T-cell receptor (e.g. cytotoxic T-lymphocyte-associated antigen-4 [CTLA-4], tumor necrosis factor receptors OX-40 or CD137) or has participated in prior pembrolizumab (MK-3475) studies
  • Has a known history of Human Immunodeficiency Virus (HIV)
  • Has known active Hepatitis B or Hepatitis C
  • Has received a live vaccine within 30 days of the planned first dose of the study

About this study

Official title: A Phase II, Open-label, Single-arm, Multicenter Study to Evaluate Efficacy and Safety of Pembrolizumab Monotherapy in Subjects With Advanced Recurrent Ovarian Cancer (KEYNOTE-100)

This study will assess the efficacy and safety of pembrolizumab (MK-3475) monotherapy in female participants with recurrent ovarian cancer (ROC) who have received up to 5 prior lines of treatment including platinum-based treatment for ROC (1 to 6 total prior lines counting front line therapy). Participants will be enrolled into two separate cohorts based on the number of prior lines of treatment received for ROC. There will be no hypothesis testing in this study.

Being tested
Pembrolizumab
Keywords
Programmed Cell Death-1 (PD1, PD-1), Programmed Death-Ligand 1 (PDL1, PD-L1)
Medical subject headings
Ovarian Neoplasms, Parkinson Disease 4, Autosomal Dominant Lewy Body

What participants receive

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

  • PembrolizumabBiological

    Also called MK-3475, KEYTRUDA®

    Administered at a dose of 200 mg via IV infusion on Day 1 of each 21-day cycle

Study groups in NCT02674061
Study groupRoleWhat they receive
Cohort A: PembrolizumabExperimentalParticipants in Cohort A received 0-2 prior lines of treatment for recurrent ovarian cancer (ROC; 1-3 total prior lines including front-line treatment) and will be administered pembrolizumab at a dose of 200 mg via intravenous (IV) infusion on Day 1 of each 21-day cycle for up to 35 cycles (up to ~2 years). Qualified participants who complete 35 administrations of pembrolizumab but progress after discontinuation can initiate a second course of pembrolizumab 200 mg for up to 17 cycles (up to ~1 additional year).
Receives: Biological: Pembrolizumab
Cohort B: PembrolizumabExperimentalParticipants in Cohort B received 3-5 prior lines of treatment for ROC (4-6 total prior lines including front-line treatment) and will be administered pembrolizumab at a dose of 200 mg via IV infusion on Day 1 of each 21-day cycle for up to 35 cycles (up to ~2 years). Qualified participants who complete 35 administrations of pembrolizumab but progress after discontinuation can initiate a second course of pembrolizumab 200 mg for up to 17 cycles (up to ~1 additional year)
Receives: Biological: Pembrolizumab

What is being measured

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

  1. Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) by Blinded Independent Central Review (BICR) in All Cohort A and Cohort B Participants

    ORR was defined as the percentage of participants in the analysis population who had a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: ≥30% decrease in the sum of diameters [SOD] of target lesions) using RECIST 1.1 based on BICR. ORR was analyzed by test of binomial parameter. The percentage of participants who experienced CR or PR per RECIST 1.1 by BICR is reported for all participants in Cohort A and Cohort B.

    Measured: Up to ~43 months (through database cut-off date of 18-September-2019)

  2. ORR Per RECIST 1.1 by BICR in Subgroup of Cohort A and Cohort B Participants With Programmed Cell Death Ligand -1 (PD-L1) Combined Positive Score (CPS) ≥10

    ORR was defined as the percentage of participants in the analysis population who had a CR (Disappearance of all target lesions) or a PR (≥30% decrease in SOD of target lesions) using RECIST 1.1 based on BICR. ORR was analyzed by test of binomial parameter. The percentage of participants who experienced CR or PR per RECIST 1.1 by BICR is reported here as the ORR for the subgroup of participants in Cohort A and Cohort B who had a PD-L1 biomarker positive expression defined by immunohistochemistry (IHC) as CPS ≥10.

    Measured: Up to ~43 months (through database cut-off date of 18-September-2019)

  3. ORR Per RECIST 1.1 by BICR in Subgroup of Cohort A and Cohort B Participants With PD-L1 CPS ≥1

    ORR was defined as the percentage of participants in the analysis population who had a CR (Disappearance of all target lesions) or a PR (≥30% decrease in SOD of target lesions) using RECIST 1.1 based on BICR. ORR was analyzed by test of binomial parameter. The percentage of participants who experienced CR or PR per RECIST 1.1 by BICR is reported here as the ORR for the subgroup of participants in Cohort A and Cohort B who had a PD-L1 biomarker positive expression defined by immunohistochemistry (IHC) as CPS ≥1.

    Measured: Up to ~43 months (through database cut-off date of 18-September-2019)

Secondary outcomes (90)

  1. Duration of Response (DOR) Per RECIST 1.1 by BICR in All Cohort A and Cohort B Participants

    For participants who demonstrated a confirmed CR (disappearance of all target lesions) or PR (≥30% decrease in SOD of target lesions) per RECIST 1.1 based on BICR, DOR was defined as time from first documented CR or PR until progressive disease (PD) or death, whichever occurs first. DOR for participants who didn't progress or die at time of analysis was censored at last tumor assessment. Per RECIST 1.1 PD is a ≥20% increase in target lesion SOD and absolute SOD increase of ≥5 mm. Appearance of ≥1 new lesion is also PD. DOR analyzed by Kaplan-Meier (KM) method is reported for all participants in Cohort A and Cohort B who had a confirmed CR or PR per RECIST 1.1 by BICR.

    Measured: Up to ~43 months (through database cut-off date of 18-September-2019)

  2. DOR Per RECIST 1.1 by BICR in Subgroup of Cohort A and Cohort B Participants With PD-L1 CPS ≥10

    For participants who demonstrated a confirmed CR (disappearance of all target lesions) or PR (≥30% decrease in SOD of target lesions) per RECIST 1.1 based on BICR, DOR was defined as time from first documented CR or PR until PD or death, whichever occurs first. DOR for participants who didn't progress or die at time of analysis was censored at last tumor assessment. Per RECIST 1.1 PD was defined as ≥20% increase in target lesion SOD and absolute SOD increase of ≥5 mm. Appearance of ≥1 new lesion is also PD. DOR analyzed by KM method is reported for the subgroup of participants in Cohort A and Cohort B who had a PD-L1 biomarker positive expression defined by IHC as CPS ≥10 and had a confirmed CR or PR per RECIST 1.1 by BICR.

    Measured: Up to ~43 months (through database cut-off date of 18-September-2019)

  3. DOR Per RECIST 1.1 by BICR in Subgroup of Cohort A and Cohort B Participants With PD-L1 CPS ≥1

    For participants who demonstrated a confirmed CR (disappearance of all target lesions) or PR (≥30% decrease in SOD of target lesions) per RECIST 1.1 based on BICR, DOR was defined as time from first documented CR or PR until PD or death, whichever occurs first. DOR for participants who didn't progress or die at time of analysis was censored at last tumor assessment. Per RECIST 1.1 PD was defined as ≥20% increase in target lesion SOD and absolute SOD increase of ≥5 mm. Appearance of ≥1 new lesion is also PD. DOR analyzed by KM method is reported for the subgroup of participants in Cohort A and Cohort B who had a PD-L1 biomarker positive expression defined by IHC as CPS ≥1 and had confirmed CR or PR per RECIST 1.1 by BICR.

    Measured: Up to ~43 months (through database cut-off date of 18-September-2019)

  4. Disease Control Rate (DCR) Per RECIST 1.1 by BICR in All Cohort A and Cohort B Participants

    DCR was defined as the percentage of participants in the analysis population who had a CR (Disappearance of all target lesions) or PR (≥30% decrease in SOD of target lesions) or Stable Disease (SD: Neither sufficient shrinkage for PR nor sufficient increase for PD [at ≥20% increase in target lesion SOD and absolute SOD increase of ≥5 mm. Appearance of ≥1 new lesion is also PD]) or Non-CR/Non-PD (NN: does not qualify for CR or PD) for ≥24 weeks per RECIST 1.1 based on BICR. The percentage of participants who experienced CR, PR, SD or NN per RECIST 1.1 by BICR is reported as the DCR, analyzed by test of binomial parameter, for all participants in Cohort A and Cohort B.

    Measured: Up to ~43 months (through database cut-off date of 18-September-2019)

  5. DCR Per RECIST 1.1 by BICR in Subgroup of Cohort A and Cohort B Participants With PD-L1 CPS ≥10

    DCR was defined as the percentage of participants in the analysis population who had a CR (Disappearance of all target lesions) or PR (≥30% decrease in SOD of target lesions) or SD (Neither sufficient shrinkage for PR nor sufficient increase for PD [at ≥20% increase in target lesion SOD and absolute SOD increase of ≥5 mm. Appearance of ≥1 new lesion is also PD]) or NN (does not qualify for CR or PD) for ≥24 weeks per RECIST 1.1 based on BICR. The percentage of participants who experienced CR, PR, SD or NN per RECIST 1.1 by BICR is reported as the DCR, analyzed by test of binomial parameter, for the subgroup of participants in Cohort A and Cohort B who had a PD-L1 biomarker positive expression defined by IHC as CPS ≥10.

    Measured: Up to ~43 months (through database cut-off date of 18-September-2019)

  6. DCR Per RECIST 1.1 by BICR in Subgroup of Cohort A and Cohort B Participants With PD-L1 CPS ≥1

    DCR was defined as the percentage of participants in the analysis population who had a CR (Disappearance of all target lesions) or PR (≥30% decrease in SOD of target lesions) or SD (Neither sufficient shrinkage for PR nor sufficient increase for PD [at ≥20% increase in target lesion SOD and absolute SOD increase of ≥5 mm. Appearance of ≥1 new lesion is also PD]) or NN (does not qualify for CR or PD) for ≥24 weeks per RECIST 1.1 based on BICR. The percentage of participants who experienced CR, PR, SD or NN per RECIST 1.1 by BICR is reported as the DCR, analyzed by test of binomial parameter, for the subgroup of participants in Cohort A and Cohort B who had a PD-L1 biomarker positive expression defined by IHC as CPS ≥1.

    Measured: Up to ~43 months (through database cut-off date of 18-September-2019)

  7. Progression Free Survival (PFS) Per RECIST 1.1 by BICR in All Cohort A and Cohort B Participants

    PFS was defined as the time from first dose of study treatment to the first documented PD per RECIST 1.1 based on BICR, or death due to any cause, whichever occurred first. Per RECIST 1.1 PD was defined as ≥20% increase in SOD of target lesions and an absolute SOD increase of ≥5 mm. The appearance of ≥1 new lesion is also PD. PFS was analyzed by KM method. PFS per RECIST 1.1 by BICR is reported for all participants in Cohort A and Cohort B.

    Measured: Up to ~58.8 months (through database cut-off date of 18-March-2021)

  8. Percentage of Participants With PFS (PFS Rate) at Month 6 Per RECIST 1.1 by BICR in All Cohort A and Cohort B Participants

    PFS was defined as the time from first dose of study treatment to the first documented PD per RECIST 1.1 based on BICR, or death due to any cause, whichever occurred first. Per RECIST 1.1 PD was defined as ≥20% increase in SOD of target lesions and an absolute SOD increase of ≥5 mm. The appearance of ≥1 new lesion is also PD. The percentage of participants with PFS (PFS rate) at Month 6 per RECIST 1.1 by BICR is reported for all participants in Cohort A and Cohort B.

    Measured: Month 6

  9. Percentage of Participants With PFS (PFS Rate) at Month 12 Per RECIST 1.1 by BICR in All Cohort A and Cohort B Participants

    PFS was defined as the time from first dose of study treatment to the first documented PD per RECIST 1.1 based on BICR, or death due to any cause, whichever occurred first. Per RECIST 1.1 PD was defined as ≥20% increase in SOD of target lesions and an absolute SOD increase of ≥5 mm. The appearance of ≥1 new lesion is also PD. The percentage of participants with PFS (PFS rate) at Month 12 per RECIST 1.1 by BICR is reported for all participants in Cohort A and Cohort B.

    Measured: Month 12

  10. Percentage of Participants With PFS (PFS Rate) at Month 18 Per RECIST 1.1 by BICR in All Cohort A and Cohort B Participants

    PFS was defined as the time from first dose of study treatment to the first documented PD per RECIST 1.1 based on BICR, or death due to any cause, whichever occurred first. Per RECIST 1.1 PD was defined as ≥20% increase in SOD of target lesions and an absolute SOD increase of ≥5 mm. The appearance of ≥1 new lesion is also PD. The percentage of participants with PFS (PFS rate) at Month 18 per RECIST 1.1 by BICR is reported for all participants in Cohort A and Cohort B.

    Measured: Month 18

  11. PFS Per RECIST 1.1 by BICR in Subgroup of Cohort A and Cohort B Participants With PD-L1 CPS ≥10

    PFS was defined as the time from first dose of study treatment to the first documented PD per RECIST 1.1 based on BICR, or death due to any cause, whichever occurred first. Per RECIST 1.1 PD was defined as ≥20% increase in SOD of target lesions and an absolute SOD increase of ≥5 mm. The appearance of ≥1 new lesion is also PD. PFS was analyzed by KM method. PFS per RECIST 1.1 by BICR is reported for the subgroup of participants in Cohort A and Cohort B who had a PD-L1 biomarker positive expression defined by IHC as CPS ≥10.

    Measured: Up to ~43 months (through database cut-off date of 18-September-2019)

  12. Percentage of Participants With PFS (PFS Rate) at Month 6 Per RECIST 1.1 by BICR in Subgroup of Cohort A and Cohort B Participants With PD-L1 CPS ≥10

    PFS was defined as the time from first dose of study treatment to the first documented PD per RECIST 1.1 based on BICR, or death due to any cause, whichever occurred first. Per RECIST 1.1 PD was defined as ≥20% increase in SOD of target lesions and an absolute SOD increase of ≥5 mm. The appearance of ≥1 new lesion is also PD. The percentage of participants with PFS (PFS rate) at Month 6 per RECIST 1.1 by BICR is reported for the subgroup of participants in Cohort A and Cohort B who had a PD-L1 biomarker positive expression defined by IHC as CPS ≥10.

    Measured: Month 6

  13. Percentage of Participants With PFS (PFS Rate) at Month 12 Per RECIST 1.1 by BICR in Subgroup of Cohort A and Cohort B Participants With PD-L1 CPS ≥10

    PFS was defined as the time from first dose of study treatment to the first documented PD per RECIST 1.1 based on BICR, or death due to any cause, whichever occurred first. Per RECIST 1.1 PD was defined as ≥20% increase in SOD of target lesions and an absolute SOD increase of ≥5 mm. The appearance of ≥1 new lesion is also PD. The percentage of participants with PFS (PFS rate) at Month 12 per RECIST 1.1 by BICR is reported for the subgroup of participants in Cohort A and Cohort B who had a PD-L1 biomarker positive expression defined by IHC as CPS ≥10.

    Measured: Month 12

  14. Percentage of Participants With PFS (PFS Rate) at Month 18 Per RECIST 1.1 by BICR in Subgroup of Cohort A and Cohort B Participants With PD-L1 CPS ≥10

    PFS was defined as the time from first dose of study treatment to the first documented PD per RECIST 1.1 based on BICR, or death due to any cause, whichever occurred first. Per RECIST 1.1 PD was defined as ≥20% increase in SOD of target lesions and an absolute SOD increase of ≥5 mm. The appearance of ≥1 new lesion is also PD. The percentage of participants with PFS (PFS rate) at Month 18 per RECIST 1.1 by BICR is reported for the subgroup of participants in Cohort A and Cohort B who had a PD-L1 biomarker positive expression defined by IHC as CPS ≥10.

    Measured: Month 18

  15. PFS Per RECIST 1.1 by BICR in Subgroup of Cohort A and Cohort B Participants With PD-L1 CPS ≥1

    PFS was defined as the time from first dose of study treatment to the first documented PD per RECIST 1.1 based on BICR, or death due to any cause, whichever occurred first. Per RECIST 1.1 PD was defined as ≥20% increase in SOD of target lesions and an absolute SOD increase of ≥5 mm. The appearance of ≥1 new lesion is also PD. PFS was analyzed by KM method. PFS per RECIST 1.1 by BICR is reported for the subgroup of participants in Cohort A and Cohort B who had a PD-L1 biomarker positive expression defined by IHC as CPS ≥1.

    Measured: Up to ~43 months (through database cut-off date of 18-September-2019)

  16. Percentage of Participants With PFS (PFS Rate) at Month 6 Per RECIST 1.1 by BICR in Subgroup of Cohort A and Cohort B Participants With PD-L1 CPS ≥1

    PFS was defined as the time from first dose of study treatment to the first documented PD per RECIST 1.1 based on BICR, or death due to any cause, whichever occurred first. Per RECIST 1.1 PD was defined as ≥20% increase in SOD of target lesions and an absolute SOD increase of ≥5 mm. The appearance of ≥1 new lesion is also PD. The percentage of participants with PFS (PFS rate) at Month 6 per RECIST 1.1 by BICR is reported for the subgroup of participants in Cohort A and Cohort B who had a PD-L1 biomarker positive expression defined by IHC as CPS ≥1.

    Measured: Month 6

  17. Percentage of Participants With PFS (PFS Rate) at Month 12 Per RECIST 1.1 by BICR in Subgroup of Cohort A and Cohort B Participants With PD-L1 CPS ≥1

    PFS was defined as the time from first dose of study treatment to the first documented PD per RECIST 1.1 based on BICR, or death due to any cause, whichever occurred first. Per RECIST 1.1 PD was defined as ≥20% increase in SOD of target lesions and an absolute SOD increase of ≥5 mm. The appearance of ≥1 new lesion is also PD. The percentage of participants with PFS (PFS rate) at Month 12 per RECIST 1.1 by BICR is reported for the subgroup of participants in Cohort A and Cohort B who had a PD-L1 biomarker positive expression defined by IHC as CPS ≥1.

    Measured: Month 12

  18. Percentage of Participants With PFS (PFS Rate) at Month 18 Per RECIST 1.1 by BICR in Subgroup of Cohort A and Cohort B Participants With PD-L1 CPS ≥1

    PFS was defined as the time from first dose of study treatment to the first documented PD per RECIST 1.1 based on BICR, or death due to any cause, whichever occurred first. Per RECIST 1.1 PD was defined as ≥20% increase in SOD of target lesions and an absolute SOD increase of ≥5 mm. The appearance of ≥1 new lesion is also PD. The percentage of participants with PFS (PFS rate) at Month 18 per RECIST 1.1 by BICR is reported for the subgroup of participants in Cohort A and Cohort B who had a PD-L1 biomarker positive expression defined by IHC as CPS ≥1.

    Measured: Month 18

  19. ORR Per RECIST 1.1 by Investigator in All Cohort A and Cohort B Participants

    ORR was defined as the percentage of participants in the analysis population who had a CR (Disappearance of all target lesions) or a PR (≥30% decrease in SOD of target lesions) using RECIST 1.1 based on investigator assessment. ORR was analyzed by test of binomial parameter. The percentage of participants who experienced CR or PR per RECIST 1.1 by investigator is reported as the ORR for all participants in Cohort A and Cohort B.

    Measured: Up to ~43 months (through database cut-off date of 18-September-2019)

  20. ORR Per RECIST 1.1 by Investigator in Subgroup of Cohort A and Cohort B Participants With PD-L1 CPS ≥10

    ORR was defined as the percentage of participants in the analysis population who had a CR (Disappearance of all target lesions) or a PR (≥30% decrease in SOD of target lesions) using RECIST 1.1 based on investigator assessment. ORR was analyzed by test of binomial parameter. The percentage of participants who experienced CR or PR per RECIST 1.1 by investigator is reported as the ORR for the subgroup of participants in Cohort A and Cohort B who had a PD-L1 biomarker positive expression defined by IHC as CPS ≥10.

    Measured: Up to ~43 months (through database cut-off date of 18-September-2019)

  21. ORR Per RECIST 1.1 by Investigator in Subgroup of Cohort A and Cohort B Participants With PD-L1 CPS ≥1

    ORR was defined as the percentage of participants in the analysis population who had a CR (Disappearance of all target lesions) or a PR (≥30% decrease in SOD of target lesions) using RECIST 1.1 based on investigator assessment. ORR was analyzed by test of binomial parameter. The percentage of participants who experienced CR or PR per RECIST 1.1 by investigator is reported as the ORR for the subgroup of participants in Cohort A and Cohort B who had a PD-L1 biomarker positive expression defined by IHC as CPS ≥1.

    Measured: Up to ~43 months (through database cut-off date of 18-September-2019)

  22. DOR Per RECIST 1.1 by Investigator in All Cohort A and Cohort B Participants

    For participants who demonstrated a confirmed CR (disappearance of all target lesions) or PR (≥30% decrease in SOD of target lesions) per RECIST 1.1 by investigator assessment, DOR was defined as time from first documented CR or PR until PD or death, whichever occurs first. DOR for participants who didn't progress or die at time of analysis was censored at last tumor assessment. Per RECIST 1.1 PD is a ≥20% increase in target lesion SOD and absolute SOD increase of ≥5 mm. Appearance of ≥1 new lesion is also PD. DOR analyzed by KM method is reported for all participants in Cohort A and Cohort B who had a confirmed CR or PR per RECIST 1.1 by investigator.

    Measured: Up to ~43 months (through database cut-off date of 18-September-2019)

  23. DOR Per RECIST 1.1 by Investigator in Subgroup of Cohort A and Cohort B Participants With PD-L1 CPS ≥10

    For participants who demonstrated a confirmed CR (disappearance of all target lesions) or PR (≥30% decrease in SOD of target lesions) per RECIST 1.1 by investigator assessment, DOR was defined as time from first documented CR or PR until PD or death, whichever occurs first. DOR for participants who didn't progress or die at time of analysis was censored at last tumor assessment. Per RECIST 1.1 PD was defined as ≥20% increase in target lesion SOD and absolute SOD increase of ≥5 mm. Appearance of ≥1 new lesion is also PD. DOR analyzed by KM method is reported for the subgroup of participants in Cohort A and Cohort B who had a PD-L1 biomarker positive expression defined by IHC as CPS ≥10 and had a confirmed CR or PR per RECIST 1.1 by investigator.

    Measured: Up to ~43 months (through database cut-off date of 18-September-2019)

  24. DOR Per RECIST 1.1 by Investigator in Subgroup of Cohort A and Cohort B Participants With PD-L1 CPS ≥1

    For participants who demonstrated a confirmed CR (disappearance of all target lesions) or PR (≥30% decrease in SOD of target lesions) per RECIST 1.1 by investigator assessment, DOR was defined as time from first documented CR or PR until PD or death, whichever occurs first. DOR for participants who didn't progress or die at time of analysis was censored at last tumor assessment. Per RECIST 1.1 PD was defined as ≥20% increase in target lesion SOD and absolute SOD increase of ≥5 mm. Appearance of ≥1 new lesion is also PD. DOR analyzed by KM method is reported for the subgroup of participants in Cohort A and Cohort B who had a PD-L1 biomarker positive expression defined by IHC as CPS ≥1 and had confirmed CR or PR per RECIST 1.1 by investigator.

    Measured: Up to ~43 months (through database cut-off date of 18-September-2019)

  25. DCR Per RECIST 1.1 by Investigator in All Cohort A and Cohort B Participants

    DCR was defined as the percentage of participants in the analysis population who had a CR (Disappearance of all target lesions) or PR (≥30% decrease in SOD of target lesions) or SD (Neither sufficient shrinkage for PR nor sufficient increase for PD [at ≥20% increase in target lesion SOD and absolute SOD increase of ≥5 mm. Appearance of ≥1 new lesion is also PD]) or NN (does not qualify for CR or PD) for ≥24 weeks per RECIST 1.1 by investigator assessment. The percentage of participants who experienced CR, PR, SD or NN per RECIST 1.1 by investigator is reported as the DCR, analyzed by test of binomial parameter, for all participants in Cohort A and Cohort B.

    Measured: Up to ~43 months (through database cut-off date of 18-September-2019)

  26. DCR Per RECIST 1.1 by Investigator in Subgroup of Cohort A and Cohort B Participants With PD-L1 CPS ≥10

    DCR was defined as the percentage of participants in the analysis population who had a CR (Disappearance of all target lesions) or PR (≥30% decrease in SOD of target lesions) or SD (Neither sufficient shrinkage for PR nor sufficient increase for PD [at ≥20% increase in target lesion SOD and absolute SOD increase of ≥5 mm. Appearance of ≥1 new lesion is also PD]) or NN (does not qualify for CR or PD) for ≥24 weeks per RECIST 1.1 by investigator assessment. The percentage of participants who experienced CR, PR, SD or NN per RECIST 1.1 by investigator is reported as the DCR, analyzed by test of binomial parameter, for the subgroup of participants in Cohort A and Cohort B who had a PD-L1 biomarker positive expression defined by IHC as CPS ≥10.

    Measured: Up to ~43 months (through database cut-off date of 18-September-2019)

  27. DCR Per RECIST 1.1 by Investigator in Subgroup of Cohort A and Cohort B Participants With PD-L1 CPS ≥1

    DCR was defined as the percentage of participants in the analysis population who had a CR (Disappearance of all target lesions) or PR (≥30% decrease in SOD of target lesions) or SD (Neither sufficient shrinkage for PR nor sufficient increase for PD [at ≥20% increase in target lesion SOD and absolute SOD increase of ≥5 mm. Appearance of ≥1 new lesion is also PD]) or NN (does not qualify for CR or PD) for ≥24 weeks per RECIST 1.1 by investigator assessment. The percentage of participants who experienced CR, PR, SD or NN per RECIST 1.1 by investigator is reported as the DCR, analyzed by test of binomial parameter, for the subgroup of participants in Cohort A and Cohort B who had a PD-L1 biomarker positive expression defined by IHC as CPS ≥1.

    Measured: Up to ~43 months (through database cut-off date of 18-September-2019)

  28. PFS Per RECIST 1.1 by Investigator in All Cohort A and Cohort B Participants

    PFS was defined as the time from first dose of study treatment to the first documented PD per RECIST 1.1 by investigator assessment, or death due to any cause, whichever occurred first. Per RECIST 1.1 PD was defined as ≥20% increase in SOD of target lesions and an absolute SOD increase of ≥5 mm. The appearance of ≥1 new lesion is also PD. PFS was analyzed by KM method. PFS per RECIST 1.1 by investigator is reported for all participants in Cohort A and Cohort B.

    Measured: Up to ~43 months (through database cut-off date of 18-September-2019)

  29. Percentage of Participants With PFS (PFS Rate) at Month 6 Per RECIST 1.1 by Investigator in All Cohort A and Cohort B Participants

    PFS was defined as the time from first dose of study treatment to the first documented PD per RECIST 1.1 by investigator assessment, or death due to any cause, whichever occurred first. Per RECIST 1.1 PD was defined as ≥20% increase in SOD of target lesions and an absolute SOD increase of ≥5 mm. The appearance of ≥1 new lesion is also PD. The percentage of participants with PFS (PFS rate) at Month 6 per RECIST 1.1 by investigator is reported for all participants in Cohort A and Cohort B.

    Measured: Month 6

  30. Percentage of Participants With PFS (PFS Rate) at Month 12 Per RECIST 1.1 by Investigator in All Cohort A and Cohort B Participants

    PFS was defined as the time from first dose of study treatment to the first documented PD per RECIST 1.1 by investigator assessment, or death due to any cause, whichever occurred first. Per RECIST 1.1 PD was defined as ≥20% increase in SOD of target lesions and an absolute SOD increase of ≥5 mm. The appearance of ≥1 new lesion is also PD. The percentage of participants with PFS (PFS rate) at Month 12 per RECIST 1.1 by investigator is reported for all participants in Cohort A and Cohort B.

    Measured: Month 12

  31. Percentage of Participants With PFS (PFS Rate) at Month 18 Per RECIST 1.1 by Investigator in All Cohort A and Cohort B Participants

    PFS was defined as the time from first dose of study treatment to the first documented PD per RECIST 1.1 by investigator assessment, or death due to any cause, whichever occurred first. Per RECIST 1.1 PD was defined as ≥20% increase in SOD of target lesions and an absolute SOD increase of ≥5 mm. The appearance of ≥1 new lesion is also PD. The percentage of participants with PFS (PFS rate) at Month 18 per RECIST 1.1 by investigator is reported for all participants in Cohort A and Cohort B.

    Measured: Month 18

  32. PFS Per RECIST 1.1 by Investigator in Subgroup of Cohort A and Cohort B Participants With PD-L1 CPS ≥10

    PFS was defined as the time from first dose of study treatment to the first documented PD per RECIST 1.1 by investigator assessment, or death due to any cause, whichever occurred first. Per RECIST 1.1 PD was defined as ≥20% increase in SOD of target lesions and an absolute SOD increase of ≥5 mm. The appearance of ≥1 new lesion is also PD. PFS was analyzed by KM method. PFS per RECIST 1.1 by investigator is reported here for the subgroup of participants in Cohort A and Cohort B who had a PD-L1 biomarker positive expression defined by IHC as CPS ≥10.

    Per protocol PFS per RECIST 1.1 by investigator was analyzed in the subgroup of Cohort A and Cohort B participants with CPS ≥10.

    Measured: Up to ~43 months (through database cut-off date of 18-September-2019)

  33. Percentage of Participants With PFS (PFS Rate) at Month 6 Per RECIST 1.1 by Investigator in Subgroup of Cohort A and Cohort B Participants With PD-L1 CPS ≥10

    PFS was defined as the time from first dose of study treatment to the first documented PD per RECIST 1.1 by investigator assessment, or death due to any cause, whichever occurred first. Per RECIST 1.1 PD was defined as ≥20% increase in SOD of target lesions and an absolute SOD increase of ≥5 mm. The appearance of ≥1 new lesion is also PD. The percentage of participants with PFS (PFS rate) at Month 6 per RECIST 1.1 by investigator is reported for the subgroup of participants in Cohort A and Cohort B who had a PD-L1 biomarker positive expression defined by IHC as CPS ≥10.

    Measured: Month 6

  34. Percentage of Participants With PFS (PFS Rate) at Month 12 Per RECIST 1.1 by Investigator in Subgroup of Cohort A and Cohort B Participants With PD-L1 CPS ≥10

    PFS was defined as the time from first dose of study treatment to the first documented PD per RECIST 1.1 by investigator assessment, or death due to any cause, whichever occurred first. Per RECIST 1.1 PD was defined as ≥20% increase in SOD of target lesions and an absolute SOD increase of ≥5 mm. The appearance of ≥1 new lesion is also PD. The percentage of participants with PFS (PFS rate) at Month 12 per RECIST 1.1 by investigator is reported for the subgroup of participants in Cohort A and Cohort B who had a PD-L1 biomarker positive expression defined by IHC as CPS ≥10.

    Measured: Month 12

  35. Percentage of Participants With PFS (PFS Rate) at Month 18 Per RECIST 1.1 by Investigator in Subgroup of Cohort A and Cohort B Participants With PD-L1 CPS ≥10

    PFS was defined as the time from first dose of study treatment to the first documented PD per RECIST 1.1 by investigator assessment, or death due to any cause, whichever occurred first. Per RECIST 1.1 PD was defined as ≥20% increase in SOD of target lesions and an absolute SOD increase of ≥5 mm. The appearance of ≥1 new lesion is also PD. The percentage of participants with PFS (PFS rate) at Month 18 per RECIST 1.1 by investigator is reported for the subgroup of participants in Cohort A and Cohort B who had a PD-L1 biomarker positive expression defined by IHC as CPS ≥10.

    Measured: Month 18

  36. PFS Per RECIST 1.1 by Investigator in Subgroup of Cohort A and Cohort B Participants With PD-L1 CPS ≥1

    PFS was defined as the time from first dose of study treatment to the first documented PD per RECIST 1.1 by investigator assessment, or death due to any cause, whichever occurred first. Per RECIST 1.1 PD was defined as ≥20% increase in SOD of target lesions and an absolute SOD increase of ≥5 mm. The appearance of ≥1 new lesion is also PD. PFS was analyzed by KM method. PFS per RECIST 1.1 by investigator is reported for the subgroup of participants in Cohort A and Cohort B who had a PD-L1 biomarker positive expression defined by IHC as CPS ≥1.

    Measured: Up to ~43 months (through database cut-off date of 18-September-2019)

  37. Percentage of Participants With PFS (PFS Rate) at Month 6 Per RECIST 1.1 by Investigator in Subgroup of Cohort A and Cohort B Participants With PD-L1 CPS ≥1

    PFS was defined as the time from first dose of study treatment to the first documented PD per RECIST 1.1 by investigator assessment, or death due to any cause, whichever occurred first. Per RECIST 1.1 PD was defined as ≥20% increase in SOD of target lesions and an absolute SOD increase of ≥5 mm. The appearance of ≥1 new lesion is also PD. The percentage of participants with PFS (PFS Rate) at Month 6 per RECIST 1.1 by investigator is reported for the subgroup of participants in Cohort A and Cohort B who had a PD-L1 biomarker positive expression defined by IHC as CPS ≥1.

    Measured: Month 6

  38. Percentage of Participants With PFS (PFS Rate) at Month 12 Per RECIST 1.1 by Investigator in Subgroup of Cohort A and Cohort B Participants With PD-L1 CPS ≥1

    PFS was defined as the time from first dose of study treatment to the first documented PD per RECIST 1.1 by investigator assessment, or death due to any cause, whichever occurred first. Per RECIST 1.1 PD was defined as ≥20% increase in SOD of target lesions and an absolute SOD increase of ≥5 mm. The appearance of ≥1 new lesion is also PD. The percentage of participants with PFS (PFS Rate) at Month 12 per RECIST 1.1 by investigator is reported for the subgroup of participants in Cohort A and Cohort B who had a PD-L1 biomarker positive expression defined by IHC as CPS ≥1.

    Measured: Month 12

  39. Percentage of Participants With PFS (PFS Rate) at Month 18 Per RECIST 1.1 by Investigator in Subgroup of Cohort A and Cohort B Participants With PD-L1 CPS ≥1

    PFS was defined as the time from first dose of study treatment to the first documented PD per RECIST 1.1 by investigator assessment, or death due to any cause, whichever occurred first. Per RECIST 1.1 PD was defined as ≥20% increase in SOD of target lesions and an absolute SOD increase of ≥5 mm. The appearance of ≥1 new lesion is also PD. The percentage of participants with PFS (PFS Rate) at Month 18 per RECIST 1.1 by investigator is reported for the subgroup of participants in Cohort A and Cohort B who had a PD-L1 biomarker positive expression defined by IHC as CPS ≥1.

    Measured: Month 18

  40. ORR Per RECIST 1.1 by BICR in Subgroup of Cohort A Participants With Platinum-Free Interval (PFI)/Treatment-Free Interval (TFI) ≥3-6 Months

    ORR was defined as the percentage of participants in the analysis population who had a CR (Disappearance of all target lesions) or a PR (≥30% decrease in SOD of target lesions) using RECIST 1.1 based on BICR. ORR was analyzed by test of binomial parameter. Per protocol the percentage of participants who experienced CR or PR per RECIST 1.1 by BICR is reported as the ORR for the subgroup of Cohort A participants with PFI/TFI (duration from end of treatment to disease recurrence) ≥3-6 months. Per protocol PFI/TFI >3-6 months subgroup analysis of ORR per RECIST 1.1 by BICR was not planned or executed in Cohort B.

    Measured: Up to ~43 months (through database cut-off date of 18-September-2019)

  41. ORR Per RECIST 1.1 by BICR in Subgroup of Cohort A Participants With PFI/ TFI >6-12 Months

    ORR was defined as the percentage of participants in the analysis population who had a CR (Disappearance of all target lesions) or a PR (≥30% decrease in SOD of target lesions) using RECIST 1.1 based on BICR. ORR was analyzed by test of binomial parameter. Per protocol the percentage of participants who experienced CR or PR per RECIST 1.1 by BICR is reported as the ORR for the subgroup of Cohort A participants with PFI/TFI (duration from end of treatment to disease recurrence) >6-12 months. Per protocol PFI/TFI >6-12 months subgroup analysis of ORR per RECIST 1.1 by BICR was not planned or executed in Cohort B.

    Measured: Up to ~43 months (through database cut-off date of 18-September-2019)

  42. DOR Per RECIST 1.1 by BICR in Subgroup of Cohort A Participants With PFI/TFI ≥3-6 Months

    For participants who demonstrated a confirmed CR (disappearance of all target lesions) or PR (≥30% decrease in SOD of target lesions) per RECIST 1.1 based on BICR, DOR was defined as time from first documented CR or PR until PD or death, whichever occurs first. DOR for participants who didn't progress or die at time of analysis was censored at last tumor assessment. Per RECIST 1.1 PD is a ≥20% increase in target lesion SOD and absolute SOD increase of ≥5 mm. Appearance of ≥1 new lesion is also PD. Per protocol DOR analyzed by KM method is reported for the subgroup of Cohort A participants with PFI/TFI (duration from end of treatment to disease recurrence) ≥3-6 months who had a CR or PR per RECIST 1.1 by BICR. Per protocol PFI/TFI ≥3-6 months subgroup analysis of DOR per RECIST 1.1 by BICR was not planned or executed in Cohort B.

    Measured: Up to ~43 months (through database cut-off date of 18-September-2019)

  43. DOR Per RECIST 1.1 by BICR in Subgroup of Cohort A Participants With PFI/TFI >6-12 Months

    For participants who demonstrated confirmed CR (disappearance of all target lesions) or PR (≥30% decrease in SOD of target lesions) per RECIST 1.1 based on BICR, DOR was defined as time from first documented CR or PR until PD or death, whichever occurs first. DOR for participants who didn't progress or die at time of analysis was censored at last tumor assessment. Per RECIST 1.1 PD is a ≥20% increase in target lesion SOD and absolute SOD increase of ≥5 mm. Appearance of ≥1 new lesion is also PD. Per protocol DOR analyzed by KM method is reported for the subgroup of Cohort A participants with PFI/TFI (duration from end of treatment to disease recurrence) >6-12 months who had a CR or PR per RECIST 1.1 by BICR. Per protocol PFI/TFI >6-12 months subgroup analysis of DOR per RECIST 1.1 by BICR was not planned or executed in Cohort B.

    Measured: Up to ~43 months (through database cut-off date of 18-September-2019)

  44. DCR Per RECIST 1.1 by BICR in Subgroup of Cohort A Participants With PFI/TFI ≥3-6 Months

    DCR was defined as the percentage of participants in the analysis population who have a CR (Disappearance of all target lesions) or PR (≥30% decrease in SOD of target lesions) or SD (Neither sufficient shrinkage for PR nor sufficient increase for PD [at ≥20% increase in target lesion SOD and absolute SOD increase of ≥5 mm. Appearance of ≥1 new lesion is also PD]) or NN (does not qualify for CR or PD) for ≥24 weeks per RECIST 1.1 based on BICR. Per protocol the percentage of participants who experienced CR, PR, SD or NN per RECIST 1.1 by BICR is reported as the DCR, analyzed by test of binomial parameter, for the subgroup of Cohort A participants with PFI/TFI (duration from end of treatment to disease recurrence) ≥3-6 months. Per protocol PFI/TFI ≥3-6 months subgroup analysis of DCR per RECIST 1.1 by BICR was not planned or executed in Cohort B.

    Measured: Up to ~43 months (through database cut-off date of 18-September-2019)

  45. DCR Per RECIST 1.1 by BICR in Subgroup of Cohort A Participants With PFI/TFI >6-12 Months

    DCR was defined as the percentage of participants in the analysis population who have a CR (Disappearance of all target lesions) or PR (≥30% decrease in SOD of target lesions) or SD (Neither sufficient shrinkage to for PR nor sufficient increase for PD [at ≥20% increase in target lesion SOD and absolute SOD increase of ≥5 mm. Appearance of ≥1 new lesion is also PD]) or NN (does not qualify for CR or PD) for ≥24 weeks per RECIST 1.1 based on BICR. Per protocol the percentage of participants who experienced CR, PR, SD or NN per RECIST 1.1 by BICR is reported as the DCR, analyzed by test of binomial parameter, for the subgroup of Cohort A participants with PFI/TFI (duration from end of treatment to disease recurrence) >6-12 months. Per protocol PFI/TFI >6-12 months subgroup analysis of DCR per RECIST 1.1 by BICR was not planned or executed in Cohort B.

    Measured: Up to ~43 months (through database cut-off date of 18-September-2019)

  46. PFS Per RECIST 1.1 by BICR in Subgroup of Cohort A Participants With PFI/TFI ≥3-6 Months

    PFS was defined as the time from first dose of study treatment to the first documented PD per RECIST 1.1 based on BICR, or death due to any cause, whichever occurred first. Per RECIST 1.1 PD was defined as ≥20% increase in SOD of target lesions and an absolute SOD increase of ≥5 mm. The appearance of ≥1 new lesion is also PD. PFS was analyzed by KM method. Per protocol PFS per RECIST 1.1 by BICR is reported for the subgroup of Cohort A participants with PFI/TFI (duration from end of treatment to disease recurrence) ≥3-6 months. Per protocol PFI/TFI ≥3-6 months subgroup analysis of PFS per RECIST 1.1 by BICR was not planned or executed in Cohort B.

    Measured: Up to ~43 months (through database cut-off date of 18-September-2019)

  47. Percentage of Participants With PFS (PFS Rate) at Month 6 Per RECIST 1.1 by BICR in Subgroup of Cohort A Participants With PFI/TFI ≥3-6 Months

    PFS was defined as the time from first dose of study treatment to the first documented PD per RECIST 1.1 based on BICR, or death due to any cause, whichever occurred first. Per RECIST 1.1 PD was defined as ≥20% increase in SOD of target lesions and an absolute SOD increase of ≥5 mm. The appearance of ≥1 new lesion is also PD. Per protocol the percentage of participants with PFS (PFS rate) at Month 6 per RECIST 1.1 by BICR is reported for the subgroup of Cohort A participants with PFI/TFI (duration from end of treatment to disease recurrence) ≥3-6 months. Per protocol PFI/TFI ≥3-6 months subgroup analysis of PFS rate at Month 6 per RECIST 1.1 by BICR was not planned or executed in Cohort B.

    Measured: Month 6

  48. Percentage of Participants With PFS (PFS Rate) at Month 12 Per RECIST 1.1 by BICR in Subgroup of Cohort A Participants With PFI/TFI ≥3-6 Months

    PFS was defined as the time from first dose of study treatment to the first documented PD per RECIST 1.1 based on BICR, or death due to any cause, whichever occurred first. Per RECIST 1.1 PD was defined as ≥20% increase in SOD of target lesions and an absolute SOD increase of ≥5 mm. The appearance of ≥1 new lesion is also PD. Per protocol the percentage of participants with PFS (PFS rate) at Month 12 per RECIST 1.1 by BICR is reported for the subgroup of Cohort A participants with PFI/TFI (duration from end of treatment to disease recurrence) ≥3-6 months. Per protocol PFI/TFI ≥3-6 months subgroup analysis of PFS rate at Month 12 per RECIST 1.1 by BICR was not planned or executed in Cohort B.

    Measured: Month 12

  49. Percentage of Participants With PFS (PFS Rate) at Month 18 Per RECIST 1.1 by BICR in Subgroup of Cohort A Participants With PFI/TFI ≥3-6 Months

    PFS was defined as the time from first dose of study treatment to the first documented PD per RECIST 1.1 based on BICR, or death due to any cause, whichever occurred first. Per RECIST 1.1 PD was defined as ≥20% increase in SOD of target lesions and an absolute SOD increase of ≥5 mm. The appearance of ≥1 new lesion is also PD. Per protocol the percentage of participants with PFS (PFS rate) at Month 18 per RECIST 1.1 by BICR is reported for the subgroup of Cohort A participants with PFI/TFI (duration from end of treatment to disease recurrence) ≥3-6 months. Per protocol PFI/TFI ≥3-6 months subgroup analysis of PFS rate at Month 18 per RECIST 1.1 by BICR was not planned or conducted in Cohort B.

    Measured: Month 18

  50. PFS Per RECIST 1.1 by BICR in Subgroup of Cohort A Participants With PFI/TFI >6-12 Months

    PFS was defined as the time from first dose of study treatment to the first documented PD per RECIST 1.1 based on BICR, or death due to any cause, whichever occurred first. Per RECIST 1.1 PD was defined as ≥20% increase in SOD of target lesions and an absolute SOD increase of ≥5 mm. The appearance of ≥1 new lesion is also PD. PFS was analyzed by KM method. Per protocol PFS per RECIST 1.1 by BICR is reported for the subgroup of Cohort A participants with PFI/TFI (duration from end of treatment to disease recurrence) >6-12 months. Per protocol PFI/TFI >6-12 months subgroup analysis of PFS per RECIST 1.1 by BICR was not planned or executed in Cohort B.

    Measured: Up to ~43 months (through database cut-off date of 18-September-2019)

  51. Percentage of Participants With PFS (PFS Rate) at Month 6 Per RECIST 1.1 by BICR in Subgroup of Cohort A Participants With PFI/TFI >6-12 Months

    PFS was defined as the time from first dose of study treatment to the first documented PD per RECIST 1.1 based on BICR, or death due to any cause, whichever occurred first. Per RECIST 1.1 PD was defined as ≥20% increase in SOD of target lesions and an absolute SOD increase of ≥5 mm. The appearance of ≥1 new lesion is also PD. Per protocol the percentage of participants with PFS (PFS rate) at Month 6 per RECIST 1.1 by BICR is reported for the subgroup of Cohort A participants with PFI/TFI (duration from end of treatment to disease recurrence) >6-12 months. Per protocol PFI/TFI >6-12 months subgroup analysis of PFS rate at Month 6 per RECIST 1.1 by BICR was not planned or executed in Cohort B.

    Measured: Month 6

  52. Percentage of Participants With PFS (PFS Rate) at Month 12 Per RECIST 1.1 by BICR in Subgroup of Cohort A Participants With PFI/TFI >6-12 Months

    PFS was defined as the time from first dose of study treatment to the first documented PD per RECIST 1.1 based on BICR, or death due to any cause, whichever occurred first. Per RECIST 1.1 PD was defined as ≥20% increase in SOD of target lesions and an absolute SOD increase of ≥5 mm. The appearance of ≥1 new lesion is also PD. Per protocol the percentage of participants with PFS (PFS rate) at Month 12 per RECIST 1.1 by BICR is reported for the subgroup of Cohort A participants with PFI/TFI (duration from end of treatment to disease recurrence) >6-12 months. Per protocol PFI/TFI >6-12 months subgroup analysis of PFS rate at Month 12 per RECIST 1.1 by BICR was not planned or executed in Cohort B.

    Measured: Month 12

  53. Percentage of Participants With PFS (PFS Rate) at Month 18 Per RECIST 1.1 by BICR in Subgroup of Cohort A Participants With PFI/TFI >6-12 Months

    PFS was defined as the time from first dose of study treatment to the first documented PD per RECIST 1.1 based on BICR, or death due to any cause, whichever occurred first. Per RECIST 1.1 PD was defined as ≥20% increase in SOD of target lesions and an absolute SOD increase of ≥5 mm. The appearance of ≥1 new lesion is also PD. Per protocol the percentage of participants with PFS (PFS rate) at Month 18 per RECIST 1.1 by BICR is reported for the subgroup of Cohort A participants with PFI/TFI (duration from end of treatment to disease recurrence) >6-12 months. Per protocol PFI/TFI >6-12 months subgroup analysis of PFS rate at Month 18 per RECIST 1.1 by BICR was not planned or executed in Cohort B.

    Measured: Month 18

  54. ORR Per RECIST 1.1 by Investigator in Subgroup of Cohort A Participants With PFI/ TFI ≥3-6 Months

    ORR was defined as the percentage of participants in the analysis population who had a CR (Disappearance of all target lesions) or a PR (≥30% decrease in SOD of target lesions) using RECIST 1.1 based on investigator assessment. ORR was analyzed by test of binomial parameter. Per protocol the percentage of participants who experienced CR or PR per RECIST 1.1 by investigator is reported as the ORR for the subgroup of Cohort A participants with PFI/TFI (duration from end of treatment to disease recurrence) ≥3-6 months. Per protocol PFI/TFI ≥3-6 months subgroup analysis of ORR per RECIST 1.1 by investigator was not planned or executed in Cohort B.

    Measured: Up to ~43 months (through database cut-off date of 18-September-2019)

  55. ORR Per RECIST 1.1 by Investigator in Subgroup of Cohort A Participants With PFI/ TFI >6-12 Months

    ORR was defined as the percentage of participants in the analysis population who had a CR (Disappearance of all target lesions) or a PR (≥30% decrease in SOD of target lesions) using RECIST 1.1 based on investigator assessment. ORR was analyzed by test of binomial parameter. Per protocol the percentage of participants who experienced CR or PR per RECIST 1.1 by investigator is reported as the ORR for the subgroup of Cohort A participants with PFI/TFI (duration from end of treatment to disease recurrence) >6-12 months. Per protocol PFI/TFI >6-12 months subgroup analysis of ORR per RECIST 1.1 by investigator was not planned or executed in Cohort B.

    Measured: Up to ~43 months (through database cut-off date of 18-September-2019)

  56. DOR Per RECIST 1.1 by Investigator in Subgroup of Cohort A Participants With PFI/TFI ≥3-6 Months

    For participants who demonstrated a confirmed CR (disappearance of all target lesions) or PR (≥30% decrease in SOD of target lesions) per RECIST 1.1 by investigator assessment, DOR was defined as time from first documented CR or PR until PD or death, whichever occurs first. DOR for participants who didn't progress or die at time of analysis was censored at last tumor assessment. Per RECIST 1.1 PD is ≥20% increase in target lesion SOD and absolute SOD increase of ≥5 mm. Appearance of ≥1 new lesion is also PD. Per protocol DOR analyzed by KM method is reported for the subgroup of Cohort A participants with PFI/TFI (duration from end of treatment to disease recurrence) ≥3-6 months who had a CR or PR per RECIST 1.1 by investigator. Per protocol PFI/TFI ≥3-6 months subgroup analysis of DOR per RECIST 1.1 by investigator was not planned or executed in Cohort B.

    Measured: Up to ~43 months (through database cut-off date of 18-September-2019)

  57. DOR Per RECIST 1.1 by Investigator in Subgroup of Cohort A Participants With PFI/TFI >6-12 Months

    For participants who demonstrated confirmed CR (disappearance of all target lesions) or PR (≥30% decrease in SOD of target lesions) per RECIST 1.1 by investigator assessment, DOR was defined as time from first documented CR or PR until PD or death, whichever occurs first. DOR for participants who didn't progress or die at time of analysis was censored at last tumor assessment. Per RECIST 1.1 PD is ≥20% increase in target lesion SOD and absolute SOD increase of ≥5 mm. Appearance of ≥1 new lesion is also PD. Per protocol DOR analyzed by KM method is reported for the subgroup of Cohort A participants with PFI/TFI (duration from end of treatment to disease recurrence) >6-12 months who had a CR or PR per RECIST 1.1 by investigator. Per protocol PFI/TFI >6-12 months subgroup analysis of DOR per RECIST 1.1 by investigator was not planned or executed in Cohort B.

    Measured: Up to ~43 months (through database cut-off date of 18-September-2019)

  58. DCR Per RECIST 1.1 by Investigator in Subgroup of Cohort A Participants With PFI/TFI ≥3-6 Months

    DCR was defined as the percentage of participants in the analysis population who have CR (Disappearance of all target lesions) or PR (≥30% decrease in SOD of target lesions) or SD (Neither sufficient shrinkage for PR nor sufficient increase for PD [at ≥20% increase in target lesion SOD and absolute SOD increase of ≥5 mm. Appearance of ≥1 new lesion is also PD]) or NN (doesn't qualify for CR or PD) for ≥24 weeks per RECIST 1.1 by investigator assessment. Per protocol percentage of participants who experienced CR, PR, SD or NN per RECIST 1.1 by investigator is reported as DCR, analyzed by test of binomial parameter, for subgroup of Cohort A participants with PFI/TFI (duration from end of treatment to disease recurrence) ≥3-6 months. Per protocol PFI/TFI ≥3-6 months subgroup analysis of DCR per RECIST 1.1 by investigator was not planned or executed in Cohort B.

    Measured: Up to ~43 months (through database cut-off date of 18-September-2019)

  59. DCR Per RECIST 1.1 by Investigator in Subgroup of Cohort A Participants With PFI/TFI >6-12 Months

    DCR was defined as the percentage of participants in the analysis population who have CR (Disappearance of all target lesions) or PR (≥30% decrease in SOD of target lesions) or SD (Neither sufficient shrinkage for PR nor sufficient increase for PD [at ≥20% increase in target lesion SOD and absolute SOD increase of ≥5 mm. Appearance of ≥1 new lesion is also PD]) or NN (doesn't qualify for CR or PD) for ≥24 weeks per RECIST 1.1 by investigator assessment. Per protocol percentage of participants who experienced CR, PR, SD or NN per RECIST 1.1 by investigator is reported as DCR, analyzed by test of binomial parameter, for subgroup of Cohort A participants with PFI/TFI (duration from end of treatment to disease recurrence) >6-12 months. Per protocol PFI/TFI>6-12 months subgroup analysis of DCR per RECIST 1.1 by investigator was not planned or executed in Cohort B.

    Measured: Up to ~43 months (through database cut-off date of 18-September-2019)

  60. PFS Per RECIST 1.1 by Investigator in Subgroup of Cohort A Participants With PFI/TFI ≥3-6 Months

    PFS was defined as the time from first dose of study treatment to the first documented PD per RECIST 1.1 by investigator assessment, or death due to any cause, whichever occurred first. Per RECIST 1.1 PD was defined as ≥20% increase in SOD of target lesions and an absolute SOD increase of ≥5 mm. The appearance of ≥1 new lesion is also PD. PFS was analyzed by KM method. Per protocol PFS per RECIST 1.1 by investigator is reported for the subgroup of Cohort A participants with PFI/TFI (duration from end of treatment to disease recurrence) ≥3-6 months. Per protocol PFI/TFI ≥3-6 months subgroup analysis of PFS per RECIST 1.1 by investigator was not planned or executed in Cohort B.

    Measured: Up to ~43 months (through database cut-off date of 18-September-2019)

  61. Percentage of Participants With PFS (PFS Rate) at Month 6 Per RECIST 1.1 by Investigator in Subgroup of Cohort A Participants With PFI/TFI ≥3-6 Months

    PFS was defined as the time from first dose of study treatment to the first documented PD per RECIST 1.1 by investigator assessment, or death due to any cause, whichever occurred first. Per RECIST 1.1 PD was defined as ≥20% increase in SOD of target lesions and an absolute SOD increase of ≥5 mm. The appearance of ≥1 new lesion is also PD. Per protocol the percentage of participants with PFS (PFS rate) at Month 6 per RECIST 1.1 by investigator is reported for the subgroup of Cohort A participants with PFI/TFI (duration from end of treatment to disease recurrence) ≥3-6 months. Per protocol PFI/TFI ≥3-6 months subgroup analysis of PFS rate at Month 6 per RECIST 1.1 by investigator was not planned or executed in Cohort B.

    Measured: Month 6

  62. Percentage of Participants With PFS (PFS Rate) at Month 12 Per RECIST 1.1 by Investigator in Subgroup of Cohort A Participants With PFI/TFI ≥3-6 Months

    PFS was defined as the time from first dose of study treatment to the first documented PD per RECIST 1.1 by investigator assessment, or death due to any cause, whichever occurred first. Per RECIST 1.1 PD was defined as ≥20% increase in SOD of target lesions and an absolute SOD increase of ≥5 mm. The appearance of ≥1 new lesion is also PD. Per protocol the percentage of participants with PFS (PFS rate) at Month 12 per RECIST 1.1 by investigator is reported for the subgroup of Cohort A participants with PFI/TFI (duration from end of treatment to disease recurrence) ≥3-6 months. Per protocol PFI/TFI ≥3-6 months subgroup analysis of PFS rate at Month 12 per RECIST 1.1 by investigator was not planned or executed in Cohort B.

    Measured: Month 12

  63. Percentage of Participants With PFS (PFS Rate) at Month 18 Per RECIST 1.1 by Investigator in Subgroup of Cohort A Participants With PFI/TFI ≥3-6 Months

    PFS was defined as the time from first dose of study treatment to the first documented PD per RECIST 1.1 by investigator assessment, or death due to any cause, whichever occurred first. Per RECIST 1.1 PD was defined as ≥20% increase in SOD of target lesions and an absolute SOD increase of ≥5 mm. The appearance of ≥1 new lesion is also PD. Per protocol the percentage of participants with PFS (PFS rate) at Month 18 per RECIST 1.1 by investigator is reported for the subgroup of Cohort A participants with PFI/TFI (duration from end of treatment to disease recurrence) ≥3-6 months. Per protocol PFI/TFI ≥3-6 months subgroup analysis of PFS rate at Month 18 per RECIST 1.1 by investigator was not planned or executed in Cohort B.

    Measured: Month 18

  64. PFS Per RECIST 1.1 by Investigator in Subgroup of Cohort A Participants With PFI/TFI >6-12 Months

    PFS was defined as the time from first dose of study treatment to the first documented PD per RECIST 1.1 by investigator assessment, or death due to any cause, whichever occurred first. Per RECIST 1.1 PD was defined as ≥20% increase in SOD of target lesions and an absolute SOD increase of ≥5 mm. The appearance of ≥1 new lesion is also PD. PFS was analyzed by KM method. Per protocol PFS per RECIST 1.1 by investigator is reported for the subgroup of Cohort A participants with PFI/TFI (duration from end of treatment to disease recurrence) >6-12 months. Per protocol PFI/TFI >6-12 months subgroup analysis of PFS per RECIST 1.1 by investigator was not planned or executed in Cohort B.

    Measured: Up to ~43 months (through database cut-off date of 18-September-2019)

  65. Percentage of Participants With PFS (PFS Rate) at Month 6 Per RECIST 1.1 by Investigator in Subgroup of Cohort A Participants With PFI/TFI >6-12 Months

    PFS was defined as the time from first dose of study treatment to the first documented PD per RECIST 1.1 by investigator assessment, or death due to any cause, whichever occurred first. Per RECIST 1.1 PD was defined as ≥20% increase in SOD of target lesions and an absolute SOD increase of ≥5 mm. The appearance of ≥1 new lesion is also PD. Per protocol the percentage of participants with PFS (PFS rate) at Month 6 per RECIST 1.1 by investigator is reported for the subgroup of Cohort A participants with PFI/TFI (duration from end of treatment to disease recurrence) >6-12 months. Per protocol PFI/TFI >6-12 months subgroup analysis of PFS rate at Month 6 per RECIST 1.1 by investigator was not planned or executed in Cohort B.

    Measured: Month 6

  66. Percentage of Participants With PFS (PFS Rate) at Month 12 Per RECIST 1.1 by Investigator in Subgroup of Cohort A Participants With PFI/TFI >6-12 Months

    PFS was defined as the time from first dose of study treatment to the first documented PD per RECIST 1.1 by investigator assessment, or death due to any cause, whichever occurred first. Per RECIST 1.1 PD was defined as ≥20% increase in SOD of target lesions and an absolute SOD increase of ≥5 mm. The appearance of ≥1 new lesion is also PD. Per protocol the percentage of participants with PFS (PFS rate) at Month 12 per RECIST 1.1 by investigator is reported for the subgroup of Cohort A participants with PFI/TFI (duration from end of treatment to disease recurrence) >6-12 months. Per protocol PFI/TFI >6-12 months subgroup analysis of PFS rate at Month 12 per RECIST 1.1 by investigator was not planned or executed in Cohort B.

    Measured: Month 12

  67. Percentage of Participants With PFS (PFS Rate) at Month 18 Per RECIST 1.1 by Investigator in Subgroup of Cohort A Participants With PFI/TFI >6-12 Months

    PFS was defined as the time from first dose of study treatment to the first documented PD per RECIST 1.1 by investigator assessment, or death due to any cause, whichever occurred first. Per RECIST 1.1 PD was defined as ≥20% increase in SOD of target lesions and an absolute SOD increase of ≥5 mm. The appearance of ≥1 new lesion is also PD. Per protocol the percentage of participants with PFS (PFS rate) at Month 18 per RECIST 1.1 by investigator is reported for the subgroup of Cohort A participants with PFI/TFI (duration from end of treatment to disease recurrence) >6-12 months. Per protocol PFI/TFI >6-12 months subgroup analysis of PFS rate at Month 18 per RECIST 1.1 by investigator was not planned or executed in Cohort B.

    Measured: Month 18

  68. Overall Survival (OS) in All Cohort A and Cohort B Participants

    OS was defined as the time from the first dose of study drug to death due to any cause. OS analyzed by KM method is reported for all participants in Cohort A and Cohort B.

    Measured: Up to ~58.8 months (through database cut-off date of 18-March-2021)

  69. Percentage of Participants With OS (OS Rate) at Month 6 in All Cohort A and Cohort B Participants

    OS was defined as the time from the first dose of study drug to death due to any cause. The percentage of participants with OS (OS rate) at Month 6 is reported for all participants in Cohort A and Cohort B.

    Measured: Month 6

  70. Percentage of Participants With OS (OS Rate) at Month 12 in All Cohort A and Cohort B Participants

    OS was defined as the time from the first dose of study drug to death due to any cause. The percentage of participants with OS (OS rate) at Month 12 is reported for all participants in Cohort A and Cohort B.

    Measured: Month 12

  71. Percentage of Participants With OS (OS Rate) at Month 18 in All Cohort A and Cohort B Participants

    OS was defined as the time from the first dose of study drug to death due to any cause. The percentage of participants with OS (OS rate) at Month 18 is reported for all participants in Cohort A and Cohort B.

    Measured: Month 18

  72. Percentage of Participants With OS (OS Rate) at Month 24 in All Cohort A and Cohort B Participants

    OS was defined as the time from the first dose of study drug to death due to any cause. The percentage of participants with OS (OS rate) at Month 24 is reported for all participants in Cohort A and Cohort B.

    Measured: Month 24

  73. OS in Subgroup of Cohort A and Cohort B Participants With PD-L1 CPS ≥10

    OS was defined as the time from the first dose of study drug to death due to any cause. OS analyzed by KM method is reported for the subgroup of participants in Cohort A and Cohort B who had a PD-L1 biomarker positive expression defined by IHC as CPS ≥10.

    Measured: Up to ~43 months (through database cut-off date of 18-September-2019)

  74. Percentage of Participants With OS (OS Rate) at Month 6 in Subgroup of Cohort A and Cohort B Participants With PD-L1 CPS ≥10

    OS was defined as the time from the first dose of study drug to death due to any cause. The percentage of participants with OS (OS rate) at Month 6 is reported for the subgroup of participants in Cohort A and Cohort B who had a PD-L1 biomarker positive expression defined by IHC as CPS ≥10.

    Measured: Month 6

  75. Percentage of Participants With OS (OS Rate) at Month 12 in Subgroup of Cohort A and Cohort B Participants With PD-L1 CPS ≥10

    OS was defined as the time from the first dose of study drug to death due to any cause. The percentage of participants with OS (OS rate) at Month 12 is reported for the subgroup of participants in Cohort A and Cohort B who had a PD-L1 biomarker positive expression defined by IHC as CPS ≥10.

    Measured: Month 12

  76. Percentage of Participants With OS (OS Rate) at Month 18 in Subgroup of Cohort A and Cohort B Participants With PD-L1 CPS ≥10

    OS was defined as the time from the first dose of study drug to death due to any cause. The percentage of participants with OS (OS rate) at Month 18 is reported for the subgroup of participants in Cohort A and Cohort B who had a PD-L1 biomarker positive expression defined by IHC as CPS ≥10.

    Measured: Month 18

  77. OS in Subgroup of Cohort A and Cohort B Participants With PD-L1 CPS ≥1

    OS was defined as the time from the first dose of study drug to death due to any cause. OS analyzed by KM method is reported for the subgroup of participants in Cohort A and Cohort B who had a PD-L1 biomarker positive expression defined by IHC as CPS ≥1.

    Measured: Up to ~43 months (through database cut-off date of 18-September-2019)

  78. Percentage of Participants With OS (OS Rate) at Month 6 in Subgroup of Cohort A and Cohort B Participants With PD-L1 CPS ≥1

    OS was defined as the time from the first dose of study drug to death due to any cause. The percentage of participants with OS (OS rate) at Month 6 is reported for the subgroup of participants in Cohort A and Cohort B who had a PD-L1 biomarker positive expression defined by IHC as CPS ≥1.

    Measured: Month 6

  79. Percentage of Participants With OS (OS Rate) at Month 12 in Subgroup of Cohort A and Cohort B Participants With PD-L1 CPS ≥1

    OS was defined as the time from the first dose of study drug to death due to any cause. The percentage of participants with OS (OS rate) at Month 12 is reported for the subgroup of participants in Cohort A and Cohort B who had a PD-L1 biomarker positive expression defined by IHC as CPS ≥1.

    Measured: Month 12

  80. Percentage of Participants With OS (OS Rate) at Month 18 in Subgroup of Cohort A and Cohort B Participants With PD-L1 CPS ≥1

    OS was defined as the time from the first dose of study drug to death due to any cause. The percentage of participants with OS (OS rate) at Month 18 is reported for the subgroup of participants in Cohort A and Cohort B who had a PD-L1 biomarker positive expression defined by IHC as CPS ≥1.

    Measured: Month 18

  81. OS in Subgroup of Cohort A Participants With PFI/TFI ≥3-6 Months

    OS was defined as the time from the first dose of study drug to death due to any cause. Per protocol OS analyzed by KM method is reported for the subgroup of Cohort A participants with PFI/TFI (duration from end of treatment to disease recurrence) ≥3-6 months. Per protocol PFI/TFI ≥3-6 months subgroup analysis of OS was not planned or executed in Cohort B.

    Measured: Up to ~43 months (through database cut-off date of 18-September-2019)

  82. Percentage of Participants With OS (OS Rate) at Month 6 in Subgroup of Cohort A Participants With PFI/TFI ≥3-6 Months

    OS was defined as the time from the first dose of study drug to death due to any cause. Per protocol the percentage of participants with OS (OS rate) at Month 6 is reported for the subgroup of Cohort A participants with PFI/TFI (duration from end of treatment to disease recurrence) ≥3-6 months. Per protocol PFI/TFI ≥3-6 months subgroup analysis of OS rate at Month 6 was not planned or executed in Cohort B.

    Measured: Month 6

  83. Percentage of Participants With OS (OS Rate) at Month 12 in Subgroup of Cohort A Participants With PFI/TFI ≥3-6 Months

    OS was defined as the time from the first dose of study drug to death due to any cause. Per protocol the percentage of participants with OS (OS rate) at Month 12 is reported for the subgroup of Cohort A participants with PFI/TFI (duration from end of treatment to disease recurrence) ≥3-6 months. Per protocol PFI/TFI ≥3-6 months subgroup analysis of OS rate at Month 12 was not planned or executed in Cohort B.

    Measured: Month 12

  84. Percentage of Participants With OS (OS Rate) at Month 18 in Subgroup of Cohort A Participants With PFI/TFI ≥3-6 Months

    OS was defined as the time from the first dose of study drug to death due to any cause. Per protocol the percentage of participants with OS (OS rate) at Month 18 is reported for the subgroup of Cohort A participants with PFI/TFI (duration from end of treatment to disease recurrence) ≥3-6 months. Per protocol PFI/TFI ≥3-6 months subgroup analysis of OS rate at Month 18 was not planned or executed in Cohort B.

    Measured: Month 18

  85. OS in Subgroup of Cohort A Participants With PFI/TFI >6-12 Months

    OS was defined as the time from the first dose of study drug to death due to any cause. Per protocol OS analyzed by KM method is reported for the subgroup of Cohort A participants with PFI/TFI (duration from end of treatment to disease recurrence) >6-12 months. Per protocol PFI/TFI >6-12 months subgroup analysis of OS was not planned or executed in Cohort B.

    Measured: Up to ~43 months (through database cut-off date of 18-September-2019)

  86. Percentage of Participants With OS (OS Rate) at Month 6 in Subgroup of Cohort A Participants With PFI/TFI >6-12 Months

    OS was defined as the time from the first dose of study drug to death due to any cause. Per protocol the percentage of participants with OS (OS rate) at Month 6 is reported for the subgroup of Cohort A participants with PFI/TFI (duration from end of treatment to disease recurrence) >6-12 months. Per protocol PFI/TFI >6-12 months subgroup analysis of OS rate at Month 6 was not planned or executed in Cohort B.

    Measured: Month 6

  87. Percentage of Participants With OS (OS Rate) at Month 12 in Subgroup of Cohort A Participants With PFI/TFI >6-12 Months

    OS was defined as the time from the first dose of study drug to death due to any cause. Per protocol the percentage of participants with OS (OS rate) at Month 12 is reported for the subgroup of Cohort A participants with PFI/TFI (duration from end of treatment to disease recurrence) >6-12 months. Per protocol PFI/TFI >6-12 months subgroup analysis of OS rate at Month 12 was not planned or executed in Cohort B.

    Measured: Month 12

  88. Percentage of Participants With OS (OS Rate) at Month 18 in Subgroup of Cohort A Participants With PFI/TFI >6-12 Months

    OS was defined as the time from the first dose of study drug to death due to any cause. Per protocol the percentage of participants with OS (OS rate) at Month 18 is reported for the subgroup of Cohort A participants with PFI/TFI (duration from end of treatment to disease recurrence) >6-12 months. Per protocol PFI/TFI >6-12 months subgroup analysis of OS rate at Month 18 was not planned or executed in Cohort B.

    Measured: Month 18

  89. Number of Participants Who Experienced an Adverse Event (AE)

    An AE was defined as any untoward medical occurrence in a pharmaceutical product which does not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a pre-existing condition that was temporally associated with the use of the Sponsor's product was also an AE. As specified by the protocol, the number of participants who experienced at least one AE is reported here for all participants in Cohort A and Cohort B.

    Measured: Up to ~58.8 months (through database cut-off date of 18-March-2021)

  90. Number of Participants Who Discontinued Study Treatment Due to an AE

    An AE was defined as any untoward medical occurrence in a pharmaceutical product which does not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a pre-existing condition that was temporally associated with the use of the Sponsor's product was also an AE. As specified by the protocol, the number of participants who discontinued study treatment due to an AE is reported here for all participants in Cohort A and Cohort B.

    Measured: Up to ~58.8 months (through database cut-off date of 18-March-2021)

Timeline

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

  1. First posted4 Feb 2016 (estimated)
  2. Study start25 Feb 2016
  3. Primary completion18 Sep 2019
  4. Study completion18 Mar 2021

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 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
376 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02674061
Sponsor's protocol ID
3475-100
Other IDs
2015-003338-29, 163237, MK-3475-100, KEYNOTE-100, 2015
Status last verified
Feb 2022
First submitted
2 Feb 2016
Last updated
24 Mar 2022
Data monitoring committee
No
Individual data sharing
Yes: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Publications

  • Matulonis UA, Shapira-Frommer R, Santin AD, Lisyanskaya AS, Pignata S, Vergote I, Raspagliesi F, Sonke GS, Birrer M, Provencher DM, Sehouli J, Colombo N, Gonzalez-Martin A, Oaknin A, Ottevanger PB, Rudaitis V, Katchar K, Wu H, Keefe S, Ruman J, Ledermann JA. Antitumor activity and safety of pembrolizumab in patients with advanced recurrent ovarian cancer: results from the phase II KEYNOTE-100 study. Ann Oncol. 2019 Jul 1;30(7):1080-1087. doi: 10.1093/annonc/mdz135.

    PubMed 31046082

  • Ledermann JA, Shapira-Frommer R, Santin AD, Lisyanskaya AS, Pignata S, Vergote I, Raspagliesi F, Sonke GS, Birrer M, Provencher DM, Sehouli J, Colombo N, Gonzalez-Martin A, Oaknin A, Ottevanger PB, Rudaitis V, Kobie J, Nebozhyn M, Edmondson M, Sun Y, Cristescu R, Jelinic P, Keefe SM, Matulonis UA. Molecular determinants of clinical outcomes of pembrolizumab in recurrent ovarian cancer: Exploratory analysis of KEYNOTE-100. Gynecol Oncol. 2023 Nov;178:119-129. doi: 10.1016/j.ygyno.2023.09.012. Epub 2023 Oct 18.

    PubMed 37862791

  • Cristescu R, Aurora-Garg D, Albright A, Xu L, Liu XQ, Loboda A, Lang L, Jin F, Rubin EH, Snyder A, Lunceford J. Tumor mutational burden predicts the efficacy of pembrolizumab monotherapy: a pan-tumor retrospective analysis of participants with advanced solid tumors. J Immunother Cancer. 2022 Jan;10(1):e003091. doi: 10.1136/jitc-2021-003091.

    PubMed 35101941

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Pembrolizumab in people with Ovarian Neoplasms, run by Merck Sharp & Dohme LLC.

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 11 inclusion and 17 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 24 Mar 2022. Status can change between updates, so confirm with the study contact before making plans.

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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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 22 Sep 2020). 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?

Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) by Blinded Independent Central Review (BICR) in All Cohort A and Cohort B Participants (time frame: Up to ~43 months (through database cut-off date of 18-September-2019)). The study lists 3 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 NCT02674061, which also lists 3 linked publications.

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 24 Mar 2022.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in