Stereotactic Body Radiotherapy and Focal Adhesion Kinase Inhibitor in Advanced Pancreas Adenocarcinoma

Exclusion Criteria

• •A history of other malignancy with the exception of malignancies for which all treatment was completed at least 2 years before registration and the patient has no evidence of disease.
• •Clinical evident ascites or pleural effusion that requires therapeutic paracentesis or thoracentesis.
• •Prior treatment with a drug of the FAK inhibitor class or with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-cytotoxic T-lymphocyte associated antigen 4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways.
• •Prior anti-human antibody response (AHA or ADA).
• •Currently receiving any other investigational agents or has receive any other investigational agents within 4 weeks or 5 half-lives or planned first dose of study agents.
• •A history of allergic reactions attributed to compounds of similar chemical or biologic composition to defactinib or other agents used in the study.
• •Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy not routinely associated with chemotherapeutic regimen.
• •Requires continued use of warfarin for anticoagulation and cannot stop warfarin or be safely switched to another anticoagulant or direct oral anticoagulant
• •Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, hypertension, immunosuppression, autoimmune conditions, or underlying pulmonary disease.
• •Has an active autoimmune disease requiring systemic treatment within the past 2 years (i.e. with 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.
• •Received a live vaccine within 30 days prior to the first study treatment. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g. FluMist) are live attenuated vaccines and are not allowed.
• •Known history of hepatitis B (defined as hepatitis B surface antigen \[HBsAg\] reactive) or known active hepatitis C virus (defined as HCV RNA \[qualitative\] is detected).
• •Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis.
• •Has a known history of active TB (bacillus tuberculosis).
• •Major surgery within 28 days prior to the first study treatment.
• •Pregnant and/or breastfeeding. Women of childbearing potential must have a negative pregnancy test within 14 days of study entry.
• •Patients with HIV are eligible unless their CD4+ T-cell counts are \< 350 cells/mcL or they have a history of AIDS-defining opportunistic infection within the 12 months prior to registration. Concurrent treatment with effective ART according to DHHS treatment guidelines is recommended.
• •Known SARS-Cov2 infection ≤28 days prior to first dose of study therapy.
• •Exposure to P-glycoprotein (P-gp) inhibitors or inducers within 14 days prior to the first dose and during the course of therapy.
• •Subjects with the inability to swallow oral medications or impaired gastrointestinal absorption due to gastrectomy or active inflammatory bowel disease.
• •Subjects with a history of hypersensitivity to any of the inactive ingredients (hydroxypropylmethylcellulose, mannitol, magnesium stearate) of the investigational product.