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

Inclusion Criteria

• 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 = = 60 mL/min using the Cockcroft-Gault Equation (= = 9.0 g/dL (= = 1500/uL (= = 100 x 10^9/L (= = 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 = = grade 3 immune-related adverse events (AE) with prior immunotherapy, with the exception of non-clinically significant lab abnormalities
• Radiotherapy = 4 weeks and was related to the most recent treatment
• Known history of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML)
• = 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: Abstine