Cemiplimab With or Without Fianlimab to Treat Older Patients With Localized or Locally Advanced MSI-H Colorectal Cancer

Evaluating a Surgical-Sparing Approach Using Cemiplimab With or Without Fianlimab to Treat Older Patients With Localized or Locally Advanced MSI-H Colorectal Cancer

The purpose of this study is to evaluate the safety and clinical activity of cemiplimab and the combination of cemiplimab/fianlimab in microsatellite unstable localized or locally advanced colorectal cancer diagnosed in patients age 70 or greater or in patients age 18 or greater considered poor candidates for surgery or unwilling to undergo surgery.

Study Overview

• Status: Recruiting
• Conditions: Colorectal Cancer
• Intervention / Treatment: Drug: Cemiplimab; Drug: Fianlimab

• Study Type: Interventional
• Enrollment (Estimated): 44
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Colleen Apostal, RN; Phone Number: 410-614-3644; Email: GIClinicalTrials@jhmi.edu

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21231
      • Recruiting
      • Johns Hopkins SKCCC
      • Principal Investigator: Eric Christenson, MD
      • Contact: Colleen Apostol, RN; Phone Number: 410-614-3644; Email: GIClinicalTrials@jhmi.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria for Cohort A and B:

• Age ≥70 years.
• Eastern Cooperative Oncology Group (ECOG) performance status 0 -2
• Have histologically proven localized or locally advanced mismatch repair deficient (dMMR) or microsatellite unstable (MSI-H) colorectal cancer.
• Must not have received any prior systemic treatment or radiation.
• Must be agreeable to endoscopic, and CT surveillance for a total of 24 months.
• Patient's acceptance to have a tumor biopsy.
• Patients must have adequate organ and marrow function defined by study-specified laboratory tests and procedures.
• LVEF assessment with documented LVEF ≥ 45% by either TTE or MUGA (TTE preferred) within 6 months from first study drug administration.
• For both Women and Men, must use acceptable form of birth control while on study.
• Ability to understand and willingness to sign a written informed consent document.

Inclusion Criteria for Cohort C and D:

• Age ≥18 years.
• Eastern Cooperative Oncology Group (ECOG) performance status 0 -3.
• Have histologically proven localized or locally advanced mismatch repair deficient (dMMR) or microsatellite unstable (MSI-H) colorectal cancer.
• Patient deemed a poor surgical candidate after evaluation by a surgeon or unwilling to undergo surgery.
• Must not have received any prior systemic treatment or radiation.
• Must be agreeable to endoscopic, and CT surveillance for a total of 24 months.
• Patient's acceptance to have a tumor biopsy.
• Patients must have adequate organ and marrow function defined by study-specified laboratory tests and procedures.
• For both Women and Men, must use acceptable form of birth control while on study.
• Ability to understand and willingness to sign a written informed consent document.

Exclusion Criteria for Cohorts A and B:

• Have received an investigational agent or used an investigational device within 28 days of the first dose of study drug.
• Have expected to require any other form of systemic or localized antineoplastic therapy while on study.
• Have had surgery within 28 days of dosing of investigational agent, excluding minor procedures (dental work, skin biopsy, etc.).
• History of prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA4, or anti-Lag-3 antibodies for any reason in the 5 years proceeding their colorectal cancer diagnosis.
• Currently using any chronic systemic steroids.
• Patient has received a live vaccine within 30 days of the first dose of study drug.
• History of severe hypersensitivity reaction to any monoclonal antibody.
• Uncontrolled intercurrent illness including, but not limited to, uncontrolled infection, symptomatic congestive heart failure, unstable angina, cardiac arrhythmia, metastatic cancer, or psychiatric illness/social situations that would limit compliance with study requirements.
• Active autoimmune disease.
• Any tissue or organ allograft, regardless of need for immunosuppression, including corneal allograft.
• Patient has a pulse oximetry of <92% on room air.
• Patient is on supplemental home oxygen.
• Has clinically significant heart disease.
• Cohort B Only: Troponin T (TnT) or troponin I (TnI) > 2x institutional ULN at baseline.
• Conditions, including alcohol or drug dependence, intercurrent illness, or lack of sufficient peripheral venous access, that would affect the patient's ability to comply with study visits and procedures.
• Unwilling or unable to follow the study schedule for any reason

Exclusion for Cohort C and D:

• Have received an investigational agent or used an investigational device within 28 days of the first dose of study drug.
• Have expected to require any other form of systemic or localized antineoplastic therapy while on study.
• Currently using any chronic systemic steroids.
• Patient has received a live vaccine within 30 days of the first dose of study drug.
• History of severe hypersensitivity reaction to any monoclonal antibody.
• Any tissue or organ allograft, regardless of need for immunosuppression, including corneal allograft.
• Patient is pregnant or breastfeeding.
• Cohort D Only: Troponin T (TnT) or troponin I (TnI) > 2x institutional ULN at baseline.
• Conditions, including alcohol or drug dependence, intercurrent illness, or lack of sufficient peripheral venous access, that would affect the patient's ability to comply with study visits and procedures.
• Participation deemed not in the best interest of the patient.
• Unwilling or unable to follow the study schedule for any reason.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort A - Cemiplimab	Drug: Cemiplimab; Patients will receive cemiplimab (350 mg administered IV) on Day 1 of each 21 day cycle for a total of 4 cycles of treatment.; Other Names: REGN2810, LIBTAYO
Experimental: Cohort B - Cemiplimab with Fianlimab	Drug: Cemiplimab; Patients will receive cemiplimab (350 mg administered IV) on Day 1 of each 21 day cycle for a total of 4 cycles of treatment.; Other Names: REGN2810, LIBTAYO; Drug: Fianlimab; Patients will receive fianlimab (1600 mg administered IV) on Day 1 of each 21 day cycle for a total of 4 cycles of treatment.; Other Names: REGN3767
Experimental: Cohort C - Cemiplimab	Drug: Cemiplimab; Patients will receive cemiplimab (350 mg administered IV) on Day 1 of each 21 day cycle for a total of 4 cycles of treatment.; Other Names: REGN2810, LIBTAYO
Experimental: Cohort D - Cemiplimab with Fianlimab	Drug: Cemiplimab; Patients will receive cemiplimab (350 mg administered IV) on Day 1 of each 21 day cycle for a total of 4 cycles of treatment.; Other Names: REGN2810, LIBTAYO; Drug: Fianlimab; Patients will receive fianlimab (1600 mg administered IV) on Day 1 of each 21 day cycle for a total of 4 cycles of treatment.; Other Names: REGN3767

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete Response Rate	Proportion of subjects with either a pathologic complete response (pCR) at the time of surgery OR a clinical complete response (cCR) at 6 months for those subjects who do not undergo surgery. pCR is defined as subjects with no viable tumor cell noted on pathological evaluation of the resection specimen. cCR is defined as an absence of visible disease on CT imaging by RECIST 1.1 and endoscopic evaluation.	6 Months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants experiencing grade 3 or above drug-related toxicities requiring treatment discontinuation	Defined using NCI CTCAE v5.0	7 Months

Collaborators and Investigators

• Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Collaborators: Regeneron Pharmaceuticals
• Investigators: Principal Investigator: Eric Christenson, MD, Sidney Kimmel Comprehensive Cancer Center Johns Hopkins Medical Institution

Study record dates

Study Major Dates

• Study Start (Actual): June 13, 2024
• Primary Completion (Estimated): May 1, 2030
• Study Completion (Estimated): May 1, 2030

Study Registration Dates

• First Submitted: January 4, 2024
• First Submitted That Met QC Criteria: January 4, 2024
• First Posted (Actual): January 16, 2024

Study Record Updates

• Last Update Posted (Actual): May 6, 2026
• Last Update Submitted That Met QC Criteria: May 5, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Carcinoma; Immunotherapy; Adenocarcinoma; Colorectal Cancer; Cemiplimab; Fianlimab; Anti-PD-1 therapy; Anti-Lag-3
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Intestinal Diseases; Neoplasms by Histologic Type; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Neoplasms, Glandular and Epithelial; Colonic Diseases; Carcinoma; Colorectal Neoplasms; Adenocarcinoma; Antineoplastic Agents, Immunological; Antineoplastic Agents; cemiplimab
• Other Study ID Numbers: J23155; IRB00415816 (Other Identifier: Johns Hopkins Medical Institution)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No