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

Purpose

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.

Condition

  • Colorectal Cancer

Eligibility

Eligible Ages
Over 18 Years
Eligible Sex
All
Accepts Healthy Volunteers
No

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: - 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. - 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: - 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. - 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 Design

Phase
Phase 2
Study Type
Interventional
Allocation
Non-Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
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

Recruiting Locations

Johns Hopkins SKCCC
Baltimore 4347778, Maryland 4361885 21231
Contact:
Colleen Apostol, RN
410-614-3644
GIClinicalTrials@jhmi.edu

More Details

Status
Recruiting
Sponsor
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Study Contact

Colleen Apostal, RN
410-614-3644
GIClinicalTrials@jhmi.edu