Immune Checkpoint Inhibitor M7824 and the Immunocytokine M9241 in Combination With Stereotactic Body Radiation Therapy (SBRT) in Adults With Advanced Pancreas Cancer

Pancreatic Cancer Clinical Trial

Official title: A Phase I/II Study of the Immune Checkpoint Inhibitor M7824 and the Immunocytokine M9241 in Combination With Stereotactic Body Radiation Therapy (SBRT) in Adults With Advanced Pancreas Cancer

Status Terminated

Clinical Trial Summary

Background:

Fewer than 10 percent of people with pancreas cancer can have surgery. Surgery gives the best outcome. Radiation therapy is usually used to make surgery possible. But it does not work for most people. Adding immunotherapy might help.

Objective:

To find a safe combined dose of Bintrafusp Alfa (M7824), NHS-IL12 (M9241, and radiation and to see if it causes pancreas cancer tumors to shrink.

Eligibility:

People ages 18 and older who have pancreas cancer and cannot have curative surgery

Design:

Participants will be screened under protocol 01-C-0129 with:

Medical history

Physical exam

Heart, urine, and blood tests

Scans. For this, participants will lie in a machine that takes pictures of the body. They may receive a contrast agent by vein.

Possible tumor biopsy

Participants will take the study drugs either alone or with radiation. They will get M7824 by vein every 2 weeks. They will get M9241 injected under the skin every 4 weeks. Participants who get radiation will get it 5 days in a row the first month.

Participants will have visits every 2 weeks. They will repeat screening tests.

If participants tumors shrink, they will have surgery. If their whole tumor is removed, they will stop treatment. They will otherwise continue treatment as long as they can tolerate it and it is helping them.

Participants will have visits 1 week and 1 month after they stop treatment. Then they will be contacted by phone or email for life. If they stop treatment for a reason other than their disease getting worse, they will have scans every 12 weeks.

Clinical Trial Description

Background:

• At time of diagnosis, fewer than 10% of newly diagnosed pancreatic cancer patients present with resectable disease (patients who can undergo surgery) and patients able to undergo a margin-negative surgical resection (R0) are reported to have the most favorable outcome.

• Locally advanced, non-metastatic pancreas cancer (LAPC) is observed in up to 30% of all pancreas cancer patients at time of diagnosis (including both borderline resectable and non-resectable disease).

• The primary goal of neoadjuvant therapy in LAPC is, among tumor control and extension of survival, the conversion to resectable disease achieving a R0 resection.

• Radiation therapy (RT) is commonly used as neoadjuvant treatment for LAPC.

• However, currently used RT neoadjuvant treatment regimens result in only about 40%-60% of patients with borderline resectable pancreas cancer to undergo surgical resection, in initially unresectable LAPC patient conversion are even lower, with only 7% - 19% able to undergo resection.

• Combining immunotherapy and radiation therapy could synergistically improve anti-cancer activity.

• Bintrafusp alfa (M7824) is a bifunctional fusion protein consisting of an anti-programmed death ligand 1 (PD-L1) antibody functioning as an immune checkpoint inhibitor and the extracellular domain of transforming growth factor beta (TGF-beta) receptor type 2, a TGF-beta trap.

• The NHS-IL12 (M9241) immunocytokine is composed of 2 interleukin-12 (IL-12) heterodimers, each fused to one of the H-chains of the NHS76 antibody, which has affinity for both single- and double-stranded deoxyribonucleic acid (DNA). M9241 targets delivery of IL12, a proinflammatory cytokine that has been shown anti-tumor activity including objective responses in phase I clinical trials, to regions of tumor necrosis where DNA has become exposed, e.g., after radiation therapy.

• We hypothesize that released neo-epitopes upon increased DNA damage induced by radiation therapy together with the local proinflammatory action of M9241 will complement the anti-tumor activity of M7824 in locally advanced pancreas cancer.

Objectives:

• To determine the safety and tolerability and the recommended phase 2 dose (RP2D) of M7824 and M9241 in combination with stereotactic body radiotherapy (SBRT) as neoadjuvant/perioperative treatment in subjects with pancreas cancer.

• To determine a preliminary estimate of efficacy as best overall response (BOR) according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 of M7824 and M9241 in combination with SBRT as neoadjuvant/perioperative treatment in subjects with locally advanced pancreas cancer.

Eligibility:

• Histologically or cytologically proven pancreatic adenocarcinoma.

• Patient must be eligible to undergo stereotactic body radiation therapy (SBRT) (Cohorts 2-3).

• Patients must have measurable disease.

• Age greater than or equal to 18 years

Design:

• This is an open label Phase I/II trial. During phase I the safety and tolerability of M7824 and M9241 will be evaluated and recommended Phase II dose (RP2D) of M7824 and M9241 in combination with SBRT will be estimated. During phase II efficacy of the M7824 and M9241 in combination with SBRT will be examined.

• Patients will receive treatment in cycles consisting of 28 days (with exception of additional administer of M7824 alone in Phase IA).

• Treatment will continue until unacceptable toxicity or disease progression.

• If during treatment patient become candidate for curative surgery, treatment will be stopped and can be restarted after surgery in case if surgical exploration does not result in the successful removal of the tumor. ;

Related Conditions & MeSH terms

• Histologically or Cytologically Confirmed Pancreatic Cancer
• Metastatic Pancreatic Cancer
• Pancreatic Cancer
• Pancreatic Neoplasms
• Unresectable or Borderline Resectable Pancreatic Cancer

• NCT number: NCT04327986
• Study type: Interventional
• Source: National Institutes of Health Clinical Center (CC)
• Status: Terminated
• Phase: Phase 1/Phase 2
• Start date: June 15, 2021
• Completion date: February 3, 2022