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Metastatic Pancreatic Ductal AdenocarcinomaPhase 2NCT04493060

Niraparib and Dostarlimab for the Treatment of Germline or Somatic BRCA1/2 and PALB2 Mutated Metastatic Pancreatic Cancer

A Phase 2 study testing Dostarlimab and Niraparib in people with Metastatic Pancreatic Ductal Adenocarcinoma and Stage IV Pancreatic Cancer AJCC v8, run by Mayo Clinic at 3 sites in United States.

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 phase II trial studies how well niraparib and dostarlimab work in treating patients with germline or somatic BRCA1/2 and PALB2 mutated pancreatic cancer that has spread to other places in the body (metastatic). Niraparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Dostarlimab and Niraparib
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
22 participants
Where
3 sitesUnited States
Study dates
28 Dec 2020to 1 Jun 2025
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
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Presence of either a germline deleterious mutation or somatic deleterious mutation in any one of the genes in our proposed gene-panel as determined by any of the commercially available or institutional testing platforms. Note: The somatic mutation could be either on a tissue-based test or the circulating tumor DNA (ctDNA)-based assay. The 6 genes that would determine eligibility would be: BRCA1/2, PALB2, BARD1, RAD51c, RAD51d
  • Provide written informed consent
  • Histological/cytological confirmation of diagnosis of metastatic pancreatic ductal adenocarcinoma
  • At least one but no more than two prior lines of systemic therapy for metastatic disease (maintenance therapy is not considered a line of treatment)
  • Note: Patients who have not had any prior chemotherapy can refuse chemotherapy and be considered eligible. This refusal and their reason for refusal would have to be documented
  • Received a platinum agent as part of first or second line treatment (unless contraindicated)
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  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  • Serum creatinine =< 1.5 x upper limit of normal (ULN) or estimated glomerular filtration rate (eGFR) >= 60 mL/min using the Cockcroft-Gault Equation (=< 14 days prior to registration)
  • Hemoglobin >= 9.0 g/dL (=< 14 days prior to registration)
  • Absolute neutrophil count >= 1500/uL (=< 14 days prior to registration:)
  • Platelets >= 100 x 10^9/L (=< 14 days prior to registration)
  • Total bilirubin =< 1.5 x ULN, (2.0 x ULN for subjects with Gilbert's disease) (=< 14 days prior to registration:)
  • Aspartate transaminase (AST) and alanine transaminase (ALT) =< 2.5 x ULN (for subjects with hepatic metastases =< 5 x ULN) (=< 14 days prior to registration). Note: One time repeat testing to meet eligibility is allowed. If more testing is required, discuss with principal investigator (PI)
  • International normalized ratio (INR) or prothrombin time (PT) =< 1.5 x ULN unless patient is receiving anticoagulant therapy as long as PT or partial thromboplastin (PTT) is within therapeutic range of intended use of anticoagulants. Activated partial thromboplastin time (aPTT) =< 1.5 x ULN unless patient is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants (=< 14 days prior to registration)
  • Evaluable or measurable disease per iRECIST
  • Life expectancy of >= 3 months
  • Willingness to consent to translational studies
  • Willingness to undergo repeat biopsies of tumor lesions amenable to biopsy
  • Note: While biopsies are mandatory, subjects are allowed to participate if no lesions are amenable to biopsy, or if biopsy is not possible due to safety
  • Willingness to not donate blood during the study or for 90 days after the last dose of study treatment
  • Willingness to not breastfeed during the study or for 90 days after the last dose of study treatment
  • Negative pregnancy test done =< 7 days prior to registration, for persons of childbearing potential only

Who cannot join

  • Known hypersensitivity to any component of study treatments (either niraparib and/or TSR-042 or similar medications)
  • Prior treatment with the combination of PARP inhibition and immunotherapy (either CTLA-4 or anti-PD1/PD-L1 therapies). Prior treatment consisting of monotherapy with either PARP inhibitors and/or with immunotherapy are allowed. Treatment with PARPi or PD1 inhibitor as the most recent treatment prior to enrollment is not allowed
  • Patient experienced >= grade 3 immune-related adverse events (AE) with prior immunotherapy, with the exception of non-clinically significant lab abnormalities
  • Radiotherapy =< 2 weeks prior to first study treatment or radionuclide treatment =< 4 weeks of first study treatment
  • Live attenuated vaccine administration within 30 days prior to registration and/or expected during study period
  • Known brain metastases, uncontrolled seizure disorder, or active neurologic disease which in the opinion of the investigator would impede participation within the trial. Subjects with treated brain metastases are allowed to enroll
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  • Allogeneic bone marrow transplantation or high-dose chemotherapy requiring hematopoietic stem cell rescue
  • Received a transfusion (platelets or red blood cells) =< 4 weeks prior to registration
  • NOTE: patients are also deemed ineligible if they have received a transfusion =< 4 weeks prior to first dose of niraparib
  • Received colony-stimulating factors (e.g., granulocyte colony-stimulating factor, granulocyte macrophage colony-stimulating factor, or recombinant erythropoietin) =< 4 weeks prior to registration
  • NOTE: patients are also deemed ineligible if they have received colony-stimulating factors =< 4 weeks prior to first dose of niraparib
  • Known grade 3 or 4 anemia, neutropenia or thrombocytopenia due to prior chemotherapy that persisted > 4 weeks and was related to the most recent treatment
  • Known history of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML)
  • =< 4 weeks since receiving treatment with another investigational drug, or anti-cancer therapy, or within a time interval less than at least 5 half-lives of the investigational agent (whichever is shorter), or insufficient recovery (to the judgement of the investigator) from adverse events due to such a previously administered agent, except for alopecia prior to initiating protocol therapy. Bisphosphonate therapy and receptor activator of nuclear factor kappa-Β ligand (RANKL) inhibitors are not considered anti-cancer therapy
  • Inadequate recovery from toxicity and/or complications from previous interventions, including due to major surgery to the judgement of the investigator. Minor surgery allowed up to 3 weeks from registration
  • Primary or secondary immunodeficiency, including immunosuppressive disease, and immunosuppressive doses of corticosteroids (e.g., prednisone > 20 mg per day during 2 weeks prior to first study treatment) or other immunosuppressive medications at dose levels that to the judgement of the investigator would preclude participation within the past 4 weeks prior to registration. Subjects with human immunodeficiency virus (HIV) who are stable on highly active antiretroviral therapy (HAART) will not be excluded
  • Participant has known active hepatitis B (e.g., hepatitis B surface antigen [HBsAg] reactive) or hepatitis C (e.g., hepatitis C virus [HCV] ribonucleic acid [qualitative] is detected)
  • Pregnant or lactating
  • Clinically significant, active, bacterial infections that, to the judgement of the investigator makes it undesirable for the subject to participate in the study
  • Persons of childbearing potential (POCBP) or those capable of causing pregnancy whose sexual partners are POCBP who are unwilling or unable to use an effective method of contraception for at least 1 month prior to study entry, for the duration of the study, and for at least 180 days after the last dose of study drug. Non-childbearing potential is defined as follows (by other than medical reasons):
  • >= 45 years of age and has not had menses for > 1 year
  • Patients who have been amenorrhoeic for < 2 years without history of a hysterectomy and oophorectomy must have a follicle stimulating hormone value in the postmenopausal range upon screening evaluation
  • Post-hysterectomy, post-bilateral oophorectomy, or post-tubal ligation. Documented hysterectomy or oophorectomy must be confirmed with medical records of the actual procedure or confirmed by an ultrasound. Tubal ligation must be confirmed with medical records of the actual procedure, otherwise the patient must be willing to use an adequate barrier method throughout the study, starting with the screening visit through 180 days after the last dose of study treatment. Information must be captured appropriately within the site's source documents. Note: Abstinence is acceptable if this is the established and preferred contraception for the patient
  • History or active TB (Bacillus tuberculosis) that in the investigators opinion would preclude participation within the study
  • Any gastro-intestinal conditions that to the judgement of the investigator would interfere with the absorption of niraparib
  • Active, known or suspected unstable auto-immune disease, are excluded from this study. Exceptions to this criterion are all auto-immune disease that have remained stable within the past 3 months on corticosteroids (=< prednisone 20 mg or equivalent) prior to first study treatment are allowed to enroll. Patients with autoimmune diseases that do not require active immunosuppression are also allowed to enroll
  • Note: Paraneoplastic disease as a cause of auto-immune phenomenon will not be considered as auto-immune disease and are allowed to enroll
  • Evidence of serious uncontrolled medical disorder, active infection or mental disorder that, to the judgement of the investigator, makes it undesirable for the subject to participate in the study or that would jeopardize compliance with the protocol. Examples include, but are not limited to, uncontrolled ventricular arrhythmia, recent (within 90 days) myocardial infarction, uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome, or any psychiatric disorder that prohibits obtaining informed consent
  • Prior malignancy which required active systemic treatment within 2 years prior to first study treatment. Exceptions are: successfully treated squamous cell carcinoma of the skin, superficial bladder cancer, and in situ carcinoma of the cervix. Since patients with BRCA 1/2 or PALB2 can have other tumors, as long as they have been definitively treated, it would not be considered an exclusion

Trial locations and contacts

3 sites in 1 country.

United States3 sites
  • Mayo Clinic in Florida

    Jacksonville, Florida, 32224-9980

  • Mayo Clinic in Rochester

    Rochester, Minnesota, 55905

  • Mayo Clinic in Arizona

    Scottsdale, Arizona, 85259

Other trials in United States

About this study

Official title: Phase II Study of Niraparib and TSR-042 in Patients With Germline or Somatic BRCA1/2 and PALB2-Related Pancreatic Cancer

This phase II trial studies how well niraparib and dostarlimab work in treating patients with germline or somatic BRCA1/2 and PALB2 mutated pancreatic cancer that has spread to other places in the body (metastatic). Niraparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as dostarlimab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving niraparib and dostarlimab may kill more tumor cells.

Read the detailed description

PRIMARY OBJECTIVE:

  1. To determine antitumor activity as measured by disease control rate at 12 weeks (DCR12) as assessed using immune-modified Response Evaluation Criteria in Solid Tumors (iRECIST) in select homologous recombination repair (HRR) deficient pancreatic cancer patients with HRR deficiency (defined as mutations in BRCA 1/ 2, or PALB2).

SECONDARY OBJECTIVES:

  1. To assess adverse events according to the current National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) and other safety parameters.

II. To assess the time to next treatment (TTNT), objective response rate (ORR), time to and duration of response and duration of confirmed stable disease according to iRECIST.

III. To assess progression-free survival. IV. To assess overall survival.

CORRELATIVE RESEARCH OBJECTIVES:

  1. To assess germline deoxyribonucleic acid (DNA) and serum markers of immune response.

II. To determine changes in circulating tumor DNA (ctDNA) profile after therapy with a PARP inhibitor (i) and a PD-1 inhibitor.

III. To study mechanisms of resistance in ctDNA profile after therapy with a PARPi and a PD-1 inhibitor.

IV. To assess the tumor microenvironment for immune related changes (immune infiltration, PD-L1 and PD-1 expression, tumor-infiltrating lymphocytes [TIL]).

  1. To assess genetic profile of the tumor pre- and post-treatment. VI. To determine changes in the cytokine profile pre- and post-treatment.

OUTLINE:

Patients receive niraparib orally (PO) once daily (QD) on days 1-21. Patients also receive dostarlimab intravenously (IV) over 30 minutes on day 1 every 3 weeks (Q3W) for cycles 1-4 and every 6 weeks (Q6W) for subsequent cycles. Cycles repeat every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days, every 3 months until progressive disease (PD), and then every 6 months for up to 5 years after registration.

Being tested
Dostarlimab, Niraparib
Medical subject headings
Pancreatic Neoplasms

What participants receive

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

  • DostarlimabBiological

    Also called ANB011, Immunoglobulin G4, Anti-programmed Cell Death Protein 1 (PDCD1) (Humanized Clone ABT1 Gamma4-chain), Disulfide with Humanized Clone ABT1 Kappa-chain, Dimer, TSR 042, TSR-042

    Given IV

  • NiraparibDrug

    Also called MK-4827, MK4827

    Given PO

Study groups in NCT04493060
Study groupRoleWhat they receive
Treatment (niraparib, dostarlimab)ExperimentalPatients receive niraparib PO QD on days 1-21. Patients also receive dostarlimab IV over 30 minutes on day 1 Q3W for cycles 1-4 and Q6W for subsequent cycles. Cycles repeat every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity.
Receives: Biological: Dostarlimab; Drug: Niraparib

What is being measured

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

  1. Disease Control Rate at 12 Weeks (DCR12)

    Will be assessed using the standard immune-modified Response Evaluation Criteria in Solid Tumors (iRECIST) criteria.

    Measured: At 12 weeks

Secondary outcomes (6)
  1. Objective Response Rate (ORR)

    The confirmed response rate (by iRECIST ) will be assessed.

    Measured: Up to 4 years and 5 months

  2. Time to Next Treatment (TTNT)

    TTNT will be estimated using the Kaplan-Meier method.

    Measured: From the end of study treatment to receiving the next treatment, assessed up to 5 years

  3. Overall Survival (OS)

    OS will be estimated using the Kaplan-Meier method.

    Measured: From study entry to death from any cause, assessed up to 4 years and 5 months

  4. Time to and Duration of Confirmed Response

    Will be assessed using the Kaplan-Meier method.

    Measured: From the first documented date of confirmed response (complete response [CR] or partial response [PR]) to the date at which progression is first documented, assessed up to 5 years

  5. Progression-free Survival (PFS)

    PFS will be estimated using the Kaplan-Meier method.

    Measured: From study entry to the first of either disease progression or death from any cause, assessed up to 4 years and 5 months

  6. Incidence of Adverse Events (AEs)

    The maximum grade for each type of adverse event will be summarized using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. The frequency and percentage of grade 3+ adverse events will be estimated. Will also assess AEs at least possibly related to treatment as well.

    Measured: Up to 4 years and 5 months

Timeline

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

  1. First posted30 Jul 2020
  2. Study start28 Dec 2020
  3. Primary completion7 Dec 2023
  4. Study completion1 Jun 2025

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
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
22 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04493060
Sponsor's protocol ID
MC1841
Other IDs
NCI-2020-05352, MC1841, 18-003525
Status last verified
Aug 2026
First submitted
27 Jul 2020
Last updated
3 Sep 2026
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Dostarlimab and Niraparib in people with Metastatic Pancreatic Ductal Adenocarcinoma and Stage IV Pancreatic Cancer AJCC v8, run by Mayo Clinic at 3 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 22 inclusion and 29 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 3 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 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 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 7 Aug 2025). 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?

Disease Control Rate at 12 Weeks (DCR12) (time frame: At 12 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?
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 3 Sep 2026.

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