Cemiplimab With Fianlimab for Resectable Non-Metastatic Colon Cancer

NCT07224022 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: Pro00118775
• Study Type: interventional
• Target: 24
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is a research study to test whether two immunotherapy drugs-cemiplimab and fianlimab-can safely and effectively shrink colon tumors before surgery in people with stage II-III colon cancer that has not spread to other parts of the body. Participants will receive two doses of the study drugs through an IV (one on Day 1 and one on Day 22). During the study, participants will have regular visits to the study clinic and multiple tests for safety and research purposes, including blood tests, along with other tests and scans, followed by surgery to remove the tumor. The study will follow participants' health for up to three years after surgery. Risks of cemiplimab and fianlimab include fatigue, diarrhea, skin rash, thyroid problems, and immune-related side effects such as inflammation of the lungs, liver, or intestines.

Conditions

Colon Cancer

Keywords

Previously untreated; pMMR; MSS; Neoadjuvant; Resectable; Non-metastatic; previously untreated T4N0 or stage III pMMR/MSS colon cancer

Outcome Measures

Primary Outcomes (2)

• Feasibility of treatment with cemiplimab and fianlimab before surgery

  Measured by the proportion of patients completing surgery within 60 days after Day 1 of treatment with cemiplimab and fianlimab

  60 days after first study treatment

• Safety of treatment with cemiplimab and fianlimab before surgery

  The frequency and severity of adverse events, according to NCI CTCAE V6.0

  AEs will be assessed from Day 1 through Day 112 (90 days after the last dose of study treatment)

Secondary Outcomes (2)

• Two-year disease-free survival

  Up to two years after surgery

• Pathological Response

  Resection is to occur from 30 to 60 days after the first dose of study drug

Study Arms (1)

Cemiplimab in combination with Fianlimab

EXPERIMENTAL

All patients will be treated with fianlimab 1600 mg IV plus cemiplimab 350 mg IV on Days 1 and 22.

Drug: Cemiplimab + Fianlimab [Fixed Dose Combination (FDC)]

Interventions

Cemiplimab + Fianlimab [Fixed Dose Combination (FDC)] DRUG

Immune checkpoint inhibition with antibodies directed against PD-1 and CTLA-4 receptors have demonstrated significant and durable efficacy in several advanced malignancies. LAG-3 is classified as an immune checkpoint protein that negatively regulates T cell activity, similar to PD-1 and CTLA-4. Blockade of LAG-3 with antibodies such as fianlimab, especially in combination with anti-PD-1 therapy, may represent a potentially effective or enhanced treatment for advanced malignancies. We hypothesize that cemiplimab in combination with fianlimab is feasible, safe, and effective neoadjuvant treatment strategy for early-stage colon cancer.

Cemiplimab in combination with Fianlimab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically and/or cytologically documented adenocarcinoma of the colon
• Tumor testing indicating proficient mismatch repair and/or microsatellite stable (pMMR/MSS)
• No evidence of measurable distant metastatic disease (as per RECIST v1.1 criteria) based on CT of the chest, abdomen, and pelvis
• T4N0 or stage III colon cancer as per baseline CT imaging (see Appendix E for imaging guidelines)
• Candidate for surgical resection with curative intent
• Age ≥ 18 years
• ECOG Performance Score of 0 or 1
• Adequate marrow function as evidenced by:
• Absolute neutrophil count (ANC) ≥ 1,500/µL
• Platelets ≥ 100,000/µL
• Hemoglobin (Hgb) ≥ 8 g/dL
• Adequate renal function as evidenced by either calculated CrCL ≥ 50 mL/min using the Cockcroft-Gault formula or serum creatinine \<1.5x upper limit of normal (ULN)
• Adequate hepatic function as evidenced by:
• Total serum bilirubin \< 1.5 x ULN unless conjugated bilirubin ≤ ULN (conjugated bilirubin only needs to be tested if total bilirubin exceeds ULN)
• Aspartate aminotransferase (AST) ≤ 2.5 x ULN

You may not qualify if:

• Any previous treatment with immune checkpoint inhibitors targeting CTLA-4, PD-1 or PD-L1, or LAG3.
• Any previous surgery, chemotherapy, radiotherapy or targeted therapy for colon or rectal cancer.
• Clinical or radiographic evidence of bowel obstruction or perforation.
• In the opinion of the Principal Investigator, any medical condition (e.g., significant gastrointestinal bleeding, symptomatic disease) that would preclude participation in study activities (e.g., colonoscopy, immunotherapy, surgery).
• Uncontrolled pain related to primary colon malignancy.
• Radiotherapy to the primary tumor prior to or planned post-surgery.
• Gastrointestinal bleeding requiring a blood transfusion within 30 days of screening.
• Treatment with another investigational device or study drug or participation in another drug study within 30 days of screening. Other investigational procedures while participating in this study are excluded.
• Known hypersensitivity to the active substances or to any of the excipients.
• History of myocarditis.
• Troponin I TnI \>2x institutional ULN at baseline. Patients with TnI levels between \>1 to 2x ULN are permitted if repeat levels within 24 hours are ≤1x ULN. If TnI levels are \>1 to 2x ULN within 24 hours, the subject may undergo a cardiac evaluation and may be considered for treatment by the investigator based on the medical judgement in the patient's best interest.
• Intercurrent illnesses, including but not limited to active infections, unstable angina pectoris, symptomatic cardiovascular disease, or symptomatic congestive heart failure.
• Uncontrolled infection, including HIV, HBV, or HCV; or diagnosis of immunodeficiency that is related to or results in chronic infection.
• Patients with known HIV who have controlled infection (undetectable viral load and CD4 count above 350 either spontaneously or on a stable antiviral regimen) are permitted. For patients with controlled HIV infection, monitoring will be performed per local standards.
• Patients with known hepatitis B (HepBsAg+) who have controlled infection (serum hepatitis B virus DNA PCR that is below the limit of detection AND receiving anti-viral therapy for hepatitis B) are permitted. Patients with controlled infections must undergo periodic monitoring of HBV DNA per local standards and must remain on anti-viral therapy for at least 6 months beyond the last dose of investigational study drug.

Sponsors & Collaborators

• John Strickler, M.D.: lead
• Regeneron Pharmaceuticals: collaborator

MeSH Terms

Conditions

Colonic Neoplasms

Interventions

cemiplimab

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases

Central Study Contacts

Emily Bolch

CONTACT

+1 919-668-1861; gi-oncology-cru@dm.duke.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Medicine

Model Details: The study will be conducted in two stages: 1) Safety Run-In Cohort; 2) Expansion Cohort.

Study Record Dates

• First Submitted: October 30, 2025
• First Posted: November 3, 2025
• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): August 31, 2028
• Study Completion (Estimated): November 30, 2029
• Last Updated: May 6, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share