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

Pancreatic Cancer Clinical Trial

Official title: 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

Clinical Trial 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.

Clinical Trial 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. ;

Related Conditions & MeSH terms

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

• NCT number: NCT03451773
• Study type: Interventional
• Source: National Institutes of Health Clinical Center (CC)
• Status: Terminated
• Phase: Phase 1/Phase 2
• Start date: May 17, 2018
• Completion date: May 5, 2020