Cemiplimab plus gemcitabine for metastatic pancreatic cancer with SWI/SNF gene changes

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.

This trial will test whether adding the immunotherapy cemiplimab to the chemotherapy gemcitabine helps people with metastatic pancreatic ductal adenocarcinoma who have SWI/SNF genetic alterations and have already received one prior chemotherapy regimen.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 43 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: University of California, San Diego (Academic / other)
• Drugs / interventions: cemiplimab, chemotherapy, immunotherapy, radiation, ipilimumab, nivolumab
• Locations: 1 site (La Jolla, California)
• Trial ID: NCT06790602 on ClinicalTrials.gov

What this trial studies

This Phase 2, biomarker-driven trial gives patients with stage IV pancreatic ductal adenocarcinoma and documented SWI/SNF complex gene alterations cemiplimab together with standard gemcitabine chemotherapy. Eligible participants must have measurable disease and one prior line of systemic therapy but no prior immunotherapy. Patients receive combination treatment with regular imaging and clinical visits to monitor tumor response and safety. The trial is based on data suggesting SWI/SNF alterations may make some tumors more responsive to immune checkpoint blockade despite pancreatic cancer’s typically uninflamed tumor microenvironment.

Who should consider this trial

Good fit: Adults (≥18 years) with measurable stage IV pancreatic ductal adenocarcinoma, a documented SWI/SNF gene alteration on tumor sequencing, and one prior chemotherapy regimen (but no prior immunotherapy) are ideal candidates.

Not a fit: Patients without SWI/SNF alterations, those previously treated with immunotherapy, or those who cannot tolerate gemcitabine are unlikely to benefit from this trial.

Why it matters

Potential benefit: If successful, this combination could provide a new treatment option that improves tumor control or survival for patients with SWI/SNF‑mutated metastatic pancreatic cancer.

How similar studies have performed: Retrospective series and early reports suggest SWI/SNF alterations may sensitize tumors to checkpoint inhibitors, but prospective evidence in pancreatic cancer remains limited.

Eligibility criteria

Inclusion Criteria:

1. At least 18 years of age.
2. Ability to understand the nature of this study, comply with study and follow-up procedures, and give written informed consent.
3. Histologically or cytologically confirmed pancreatic ductal adenocarcinoma. Primary tumor can be intact or post-resection with newly developed metastatic disease.
4. Stage IV disease (measurable disease by Immunotherapeutics Response Evaluation Criteria in Solid Tumors is required).
5. Alterations in SWI/SNF complex chromatin remodeling genes (ARID1A, ARID1B, PBRM1, SMARCA4 and SMARCB1, etc.) detected by next generation sequencing performed prior to enrollment on an ultrasound-guided core biopsy of the primary tumor.
6. One previous line of therapy for pancreatic ductal adenocarcinoma (NOT immunotherapy or cellular therapy).
7. Last dose of chemotherapy administered \> 14 days prior to the initiation of study therapy.
8. Last dose of radiation therapy or administered \> 28 days prior to the initiation of study therapy.
9. Eastern Cooperative Oncology Group performance score of 0-1.
10. Adequate bone marrow function: Absolute neutrophil count ≥ 1,500 cells per microliter; Platelet count ≥ 100,000 cells per microliter; Hemoglobin ≥ 9.0 grams per deciliter.
11. Adequate hepatic function: Total bilirubin ≤ 1.5 times upper limit of normal (NOTE high bilirubin levels due to Gilbert's syndrome are allowed); Aspartate transaminase ≤ 3.0 times upper limit of normal (≤5.0 times upper limit of normal if liver metastases are present); Alanine transaminase ≤ 3.0 times upper limit of normal (≤5.0 times upper limit of normal if liver metastases are present).
12. Adequate renal function: Serum creatinine ≤ 1.5 times upper limit of normal.
13. Calculated corrected QT Interval (QTcF) average of the triplicate electrocardiograms \<470 milliseconds.
14. Participants not of child-bearing potential, or participants of child-bearing potential who agree to use adequate contraceptive measures during the study and for at least 6 months after the last cemiplimab dose; who are not breastfeeding, and who have a negative serum or urine pregnancy test within 72 hours prior to initiation of study therapy.
15. For participants able to cause a pregnancy: use of condoms or other methods to ensure effective contraception with partner during study participation and for at least 6 months after the last cemiplimab dose.

Exclusion Criteria:

1. Two or more lines of systemic or previous investigational therapy for metastatic pancreatic ductal adenocarcinoma.
2. History of any autoimmune disease requiring treatment within the past 12 months prior to enrollment.
3. History of transplanted organ/bone marrow.
4. History of interstitial lung disease.
5. History of stroke or intracranial hemorrhage within 6 months prior to enrollment.
6. History of previous malignancy (except in-situ cancer or basal or squamous cell skin cancer) within past 3 years prior to enrollment.
7. History of immune checkpoint inhibitor therapy, ever.
8. Known bleeding disorders (e.g., van Willebrand's disease or hemophilia).
9. Current use of warfarin or other vitamin K antagonists. NOTE: if therapeutic anticoagulation is necessary, low molecular weight heparin or oral factor Xa inhibitors are the anticoagulants of choice.
10. Current use of a strong cytochrome P450 3A inhibitor (for example, antifungal medications, grapefruit juice, amiodarone, etc.).
11. Presence of known central nervous system or brain metastases.
12. History of other diseases, metabolic dysfunction, physical examination findings, or clinical laboratory findings giving reasonable suspicion of a disease or condition that, in the opinion of the investigator, renders the subject at high risk from treatment complications or might affect the interpretation of the results of the study.
13. Life expectancy of \<3 months.
14. Known active, not-controlled human immunodeficiency virus, hepatitis B or hepatitis C infection or diagnosis of immunodeficiency.
15. Receipt of a live vaccine within 4 weeks of start of study medication.
16. Currently active, clinically significant cardiovascular disease, such as uncontrolled arrhythmia or Class 3 or 4 congestive heart failure as defined by the New York Heart Association Functional Classification; or a history of myocardial infarction, unstable angina, or acute coronary syndrome within 6 months prior to enrollment.
17. Major surgery within 4 weeks of the start of study treatment. Major surgeries are defined as those surgeries that require general anesthesia. Insertion of a vascular access device, biliary drainage tube, gastrointestinal stent are NOT considered major surgery.
18. Pregnancy or lactation.
19. Known allergic reactions to components of the study intervention, cemiplimab and/or gemcitabine.

Where this trial is running

La Jolla, California

• University of California, San Diego — La Jolla, California, United States (Recruiting)

Study contacts

• Principal investigator: Gregory P Botta, MD, PhD — University of California, San Diego
• Study coordinator: Gregory P Botta, MD, PhD

Conditions Pancreatic Ductal Adenocarcinoma; cemiplimab; gemcitabine; immune checkpoint inhibitors; pancreatic ductal adenocarcinoma; SWI/SNF; combination therapy; PDAC