NCT06790602

Cemiplimab Plus Gemcitabine in Patients With Metastatic Pancreatic Adenocarcinoma

A Single-arm, Open-label, Phase II Trial of Cemiplimab Plus Gemcitabine as Second-line Treatment in Patients With Metastatic Pancreatic Adenocarcinoma Harboring SWItch/Sucrose Non-Fermentable (SWI/SNF) Alterations.

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 43 (estimated)
• Sponsor: University of California, San Diego · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This is a Phase 2 trial evaluating the combination of cemiplimab with the standard of care chemotherapy agent gemcitabine for the treatment of patients with metastatic pancreatic ductal adenocarcinoma with SWItch/Sucrose Non-Fermentable (SWI/SNF) alterations who have already been treated with FOLFIRINOX (5-fluoruracil, leucovorin, irinotecan, oxaliplatin) or gemcitabine/nab-paclitaxel chemotherapy.

Detailed description

Chemotherapy with FOLFIRINOX (5-fluoruracil, leucovorin, irinotecan, oxaliplatin) or gemcitabine/nab-paclitaxel is the backbone of modern therapy of metastatic pancreatic ductal adenocarcinoma. Generally, the chemotherapy regimen is chosen based on the patient's performance status and ability to tolerate the specific side effect profiles of the two regimens. As many patients with metastatic pancreatic ductal adenocarcinoma suffer from multiple co-morbidities that develop with the disease, they are often subjected to treatment interruptions, dose reductions, and palliative single-agent therapies. Thus, better treatments are needed for this disease. A treatment modality for many cancer types is represented by immune checkpoint inhibitors. However, over 98% of pancreatic ductal adenocarcinoma are deemed 'cold', which means that they have an uninflamed tumor microenvironment incapable of spurring an immune response during therapy with immune checkpoint inhibitors. In fact, immune checkpoint inhibitors such as ipilimumab (Cytotoxic T-lymphocyte Associated protein 4 blocker) and nivolumab (Programmed Cell Death 1 blocker) have not shown efficacy in pancreatic ductal adenocarcinoma as single agents. Alterations in the chromatin remodeling complex SWI/SNF appear to sensitize tumors to immune checkpoint inhibitors and may be a surrogate biomarker of efficacy of these compounds. In retrospective studies, immune checkpoint inhibitors in SWI/SNF altered pancreatic ductal adenocarcinoma resulted in improved tumor responses and longer progression-free survival and overall survival. In addition, preclinical studies of immune checkpoint inhibitors plus gemcitabine show superior antitumor effects compared to gemcitabine alone in both orthotopic murine pancreatic cancer cell line grafts and in genetically engineered mouse models. Thus, the investigators propose a clinical trial of the immune checkpoint inhibitor cemiplimab plus standard of care gemcitabine to evaluate efficacy and safety of this combination in patients with metastatic pancreatic ductal adenocarcinoma harboring SWI/SNF alterations who did not respond or were intolerant to the standard of care chemotherapies (FOLFIRINOX or gemcitabine/nab-paclitaxel). The investigators hypothesize that the combination cemiplimab plus gemcitabine will lead to better overall survival, progression free survival, and overall response rate compared to historical controls.

Conditions

• Pancreatic Ductal Adenocarcinoma (mPDAC)

Interventions

Type	Name	Description
DRUG	Cemiplimab Plus Gemcitabine	Cemiplimab Plus Gemcitabine

Timeline

• Start date: 2026-04-01
• Primary completion: 2028-07-01
• Completion: 2029-12-01
• First posted: 2025-01-24
• Last updated: 2026-04-09

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study