Niraparib + Dostarlimab + RT in Pancreatic Cancer

Inclusion Criteria

• Histologically or cytologically confirmed metastatic adenocarcinoma of pancreatic origin.
• Age > 18 years.
• ECOG performance status ≤ 1.
• Life expectancy of greater than 3 months.
• Participants must have normal organ and marrow function as defined below:
• leukocytes ≥ 2,000/mcL
• absolute neutrophil count ≥ 1,500/mcL
• platelets ≥ 100,000/mcL
• hemoglobin ≥ 9 g/dL
• AST(SGOT)/ALT(SGPT) ≤2.5 × institutional upper limit of normal(subjects with liver metastases can have an AST (SGOT) ≤ 5 x ULN
• creatinine ≤ 1.5 x ULN OR
• creatinine clearance* ≥ 60 mL/min (if using the Cockcroft-Gault formula)
• total bilirubin ≤ 1.5 x ULN (subjects with Gilbert Syndrome can have a total bilirubin 1 year
• Patients who have been amenorrhoeic for 14 days prior to treatment start.
• One previously unirradiated lesion amenable to radiotherapy at a dose of 8 Gy x 3 and can meet dose constraints, and another unirradiated measurable lesion > 1 cm in size outside the radiation field that can be used as measurable disease.
• Patients must have had at least one line of prior treatment. Any prior line of treatment is permitted, including adjuvant.

Exclusion Criteria

Participants who meet any of the following criteria will be excluded:

• Systemic anticancer or biological therapy including prior chemotherapy, immunotherapy, targeted small molecule therapy within 14 days prior to investigational agent, or those who have not recovered (i.e., ≤ grade 1 or at baseline) from adverse events due to agents administered more than 2 weeks earlier. Participants with ≤ grade 2 neuropathy are an exception to these criteria and may qualify for the study. If the participant received major surgery, then they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
• Received investigational therapy ≥ 4 weeks, or within a time interval less than at least 5 half-lives of the investigational agent, whichever is shorter, prior initiating protocol therapy.
• Major surgery ≤ 3 weeks prior to initiating protocol therapy and/or not recovered from any surgical effects.
• Received radiation therapy encompassing >20% of the bone marrow within 2 weeks; or any radiation therapy within 1 week prior to day 1 of protocol therapy.
• Received a transfusion (platelets or red blood cells) ≤ 4 weeks prior to initiating protocol therapy
• Received colony-stimulating factors (e.g., granulocyte colony-stimulating factor, granulocyte macrophage colony-stimulating factor, or recombinant erythropoietin) within 4 weeks prior to initiating protocol therapy. Known history of 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).
• Active, known or suspected autoimmune disease that has required systemic treatment within the past 2 years other than vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger.
• Any condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease. Participants are permitted to use topical, ocular, intraarticular, intranasal, and inhalational corticosteroids (with minimal systemic absorption). Physiologic replacement doses of systemic corticosteroids are permitted, even if > 10 mg/day prednisone equivalents. A brief course of corticosteroids for prophylaxis (e.g., contrast dye allergy) or for treatment of non-autoimmune conditions (e.g., delayed-type hype