M7824 (MSB0011359C) in Combination With Gemcitabine in Adults With Previously Treated Advanced Adenocarcinoma of the Pancreas

Background: * M7824 (MSB0011359C) is an investigational agent in phase IB/II clinical development with dual activity against transforming growth factor beta (TGF)-beta signaling (TGF-beta ligand trap; extracellular domain of human TGF-beta receptor II) and immune checkpoint ligand inhibition (PD-L1 inhibition; avelumab, fully human immunoglobulin G1 (IgG1) monoclonal antibody (mAb) directed against human PD-L1) with an acceptable toxicity profile and early signals of anti-cancer activity including in pancreas cancer. * Gemcitabine (2 \<=,2 \<=-Difluorodeoxycytidine) is a standard-of-care nucleoside analogue in pancreas cancer with immunomodulatory mechanisms of actions in pancreas cancer patients. * Preclinical studies in autochthonous and syngeneic murine models have shown that TGF-beta inhibition and PD-L1 inhibition cooperate with gemcitabine to achieve reduction of tumor growth and extension of survival induce anti-tumor immunity and reprogram the immune landscape. Objectives: * To determine the safety and tolerability of M7824 in combination with gemcitabine in subjects with metastatic or locally advanced pancreas cancer. * To determine best overall response (BOR) rate according to Response Evaluation Criteria (Response Evaluation Criteria in Solid Tumors (RECIST) 1.1) in advanced pancreas cancer subjects. Eligibility: * Histologically confirmed diagnosis of adenocarcinoma of the pancreas. * Patients must have progressed on prior chemotherapeutic regimen. * Concurrent treatment with non-permitted drugs and other interventions, prior therapy with gemcitabine or any antibody / drug targeting T cell co-regulatory proteins (immune checkpoints) such as anti-PD 1, anti PD-L1, or anti-cytotoxic T lymphocyte antigen-4 (CTLA 4 antibody) is not allowed. Design: \- The proposed study is a phase IB/II study of M7824 in combination with gemcitabine in a safety run-in of 6-18 patients and, if safe and tolerated, will proceed to an expansion phase II cohort with a standard Simon Minimax design.