epacadostat, pembrolizumab, and crs-207, with or without cy/gvax pancreas in patients with metastatic pancreas cancer

Conditions: Metastatic Pancreatic Adenocarcinoma

Summary: this study will enroll patients who have metastatic pancreatic cancer and have progressed on prior chemotherapy. part 1 (dose escalation) participants will receive epacadostat/pembrolizumab/cyclophosphamide(cy)/gvax pancreas vaccine followed by epacadostat/pembrolizumab/crs-207, part 1x (dose escalation) participants will receive epacadostat/pembrolizumab/crs-207. part 2x (dose expansion) participants will receive epacadostat/pembrolizumab/crs-207. the primary objectives of this study are to determine the recommended dose of epacadostat in this combination and assess survival of subjects in both treatment groups.


Eligibility criteria:
inclusion criteria (abbreviated): * documented adenocarcinoma of the pancreas * have disease progression after prior chemotherapy for metastatic pancreas cancer (or adjuvant or neoadjuvant if progression occurred within 6 months of completing this regimen) * presence of at least one measurable lesion * patient acceptance to have a tumor biopsy of an accessible lesion at 2 time points (baseline and on study) * ecog performance status of 0 or 1 * life expectancy of greater than 3 months * adequate organ and marrow function defined by study-specified laboratory tests exclusion criteria (abbreviated): * brain metastases * clinical or radiographic ascites (some trace amount may be allowed) * rapidly progressing disease * live vaccine within 30 days of study treatment (flu vaccine allowed) * surgery within 28 days of study treatment (some exceptions for minor procedures) * use of an investigational agent or device within 28 days of study treatment. * chemotherapy, radiation, or biological cancer therapy within 14 days of study treatment. * prior treatment with anti-ctla-4, anti-pd-1, anti-pd-l1, or anti pd-l2, or with ido inhibitor. * use of growth factors within 14 days of study treatment * use of any systemic steroids within 14 days of study treatment or other immunosuppressive agents within 7 days of study treatment. * use of more than 2 g/day of acetaminophen * use of any ugt1a9 inhibitor * use of warfarin * use of maois or drugs with significant maoi activity within the 21 days of screening * history of seratonin syndome * known allergy to both penicillin and sulfa * known or suspected hypersensitivity to any monoclonal antibody or any study drug component * have artificial joints or implants that cannot be easily removed or a history of infection associated with an implant * significant or malignant pleural effusion * new pulmonary embolism, extremity deep venous thromboembolism, or portal vein thrombosis within 2 months of study enrollment * history of autoimmune disease (exceptions for graves or hashimoto's disease, vitiligo, and type i diabetes mellitus) * gastrointestinal condition that may affect drug absorption * significant heart disease or heart disease requiring antibiotic for prevention of endocarditis * history of abnormal electrocardiogram (ecg) that is deemed meaningful by the investigator * history of (non-infectious) pneumonitis that required steroids, evidence of interstitial lung disease or active, non-infectious pneumonitis * pulse oximetry of \< 92% on room air or the need for supplemental home oxygen * infection with hiv, hepatitis b or hepatitis c * other conditions, including alcohol or drug dependence, intercurrent illness, or lack of sufficient peripheral venous access that would affect the patient's ability to comply with study visits and procedures * pregnant or breastfeeding women * unwillingness or inability to follow the study schedule for any reason

Keywords: pancreatic cancer vaccine immunotherapy pembrolizumab pd-1 ido crs-207 epacadostat