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

NCT04493060 | Completed Phase 2 Results DMC FDA Drug

• 3 other identifiers: MC1841NCI-2020-0535218-003525
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 3

Brief 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. 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.

Conditions

Metastatic Pancreatic Ductal Adenocarcinoma; Stage IV Pancreatic Cancer AJCC v8

Outcome Measures

Primary Outcomes (1)

• Disease Control Rate at 12 Weeks (DCR12)

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

  At 12 weeks

Secondary Outcomes (6)

• Objective Response Rate (ORR)

  Up to 4 years and 5 months

• Time to Next Treatment (TTNT)

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

• Overall Survival (OS)

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

• Time to and Duration of Confirmed Response

  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

• Progression-free Survival (PFS)

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

Other Outcomes (6)

• Germline Deoxyribonucleic Acid (DNA) and Serum Markers of Immune Response

  Up to 5 years

• Changes in Circulating Tumor DNA (ctDNA) Profile After Therapy With a PARP Inhibitor (i) and a PD-1 Inhibitor

  Baseline up to 5 years

• Mechanisms of Resistance in ctDNA Profile After Therapy With a PARPi and a PD-1 Inhibitor

  Up to 5 years

Study Arms (1)

Treatment (niraparib, dostarlimab)

EXPERIMENTAL

Patients 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.

Biological: Dostarlimab; Drug: Niraparib

Interventions

Dostarlimab BIOLOGICAL

Given IV

Also known as: 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, TSR042

Treatment (niraparib, dostarlimab)

Niraparib DRUG

Given PO

Also known as: MK-4827, MK4827

Treatment (niraparib, dostarlimab)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)
• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Mayo Clinic: lead

Study Sites (3)

Mayo Clinic in Arizona

Scottsdale, Arizona, 85259, United States

Location

Mayo Clinic in Florida

Jacksonville, Florida, 32224-9980, United States

Location

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

Location

Related Links

• Mayo Clinic Clinical Trials

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

dostarlimab; Immunoglobulin G; Disulfides; niraparib

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Immunoglobulin Isotypes; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Sulfides; Anions; Ions; Electrolytes; Inorganic Chemicals; Hydrogen Sulfide; Sulfur Compounds; Organic Chemicals

Results Point of Contact

• Title: Dr. Robert R McWilliams
• Organization: Mayo Clinic

mcwilliams.robert@mayo.edu

507-284-2511

Study Officials

• Robert R. McWilliams, M.D.

  Mayo Clinic in Rochester

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 27, 2020
• First Posted: July 30, 2020
• Study Start: December 28, 2020
• Primary Completion: December 7, 2023
• Study Completion: June 1, 2025
• Last Updated: August 7, 2025
• Results First Posted: August 7, 2025

Record last verified: 2025-01

Locations

US (3)