NCT03451773

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

A Phase IB/II Single-arm Study of M7824 (MSB0011359C) in Combination With Gemcitabine in Adults With Previously Treated Advanced Adenocarcinoma of the Pancreas

• Status: Terminated
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 7 (actual)
• Sponsor: National Cancer Institute (NCI) · NIH
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

Background: Pancreas cancer ranks 4th in all cancer-related deaths in the United States (U.S.) Gemcitabine is a standard treatment for it. M7824 (MSB0011359C) blocks a pathway that prevents the immune system from effectively fighting cancer. The two drugs together might help people with pancreas cancer. Objective: To test if giving M7824 together with gemcitabine is safe and causes tumors to shrink. Eligibility: People ages 18 and older with pancreatic cancer already treated with standard therapies Design: Participants will be screened with: Medical history Physical exam Scans in a machine that takes pictures of the body Blood, urine, and heart tests Some participants may have a tumor sample removed. Participants will get M7824 by intravenous (IV) once every 2 weeks. They will continue until their disease gets worse or they have unacceptable side effects. After the first dose, participants will also get gemcitabine by IV once weekly for 7 weeks. Then they will get it as follows for up to 6 months: Skip 1 week, get the drug once a week for 3 weeks, skip 1 week. Before treatment on the first day of each cycle, participants will repeat screening tests. They will also have: Optional tumor biopsies before and after 3 cycles of therapy Questions about their well-being and function Genetic testing of tissue and blood samples Participants will have a follow-up visit 4-5 weeks after they stop therapy. This includes a physical exam, blood and urine tests, and maybe a scan. If their disease does not get worse, they will be invited for scans every 12 weeks.

Detailed description

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.

Conditions

• Cancer of Pancreas
• Pancreas Cancer
• Pancreatic Adenocarcinoma
• Pancreatic Cancer
• Pancreatic Neoplasms

Interventions

Type	Name	Description
DRUG	M7824	1,200 or 500mg every 2 weeks by intravenous (IV) infusion
DRUG	Gemcitabine	Standard (1,000 mg/m\^2) or reduced (600 mg/m\^2 for 4 doses) intravenous (IV) once a week for first 4 weeks. Then, once weekly for 3 weeks with one week rest. Gemcitabine will be discontinued after 6 months of therapy

Timeline

• Start date: 2018-05-17
• Primary completion: 2020-05-05
• Completion: 2020-05-05
• First posted: 2018-03-02
• Last updated: 2021-06-16
• Results posted: 2021-06-16

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study