Study of Nivolumab and Relatlimab in Patients With Microsatellite Stable (MSS) Advanced Colorectal Cancer

Johns Hopkins Medicine

Status and phase: Active, not recruiting; Phase 2

Conditions: Colorectal Adenocarcinoma; Microsatellite Stable (MSS) Colorectal Adenocarcinomas

Treatments: Drug: Relatlimab; Drug: Nivolumab

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT03642067

IRB00173537 (Other Identifier)

CA224-068 (Other Identifier)

J18119

Details and patient eligibility

About

The purpose of this study is to evaluate the safety and clinical activity of nivolumab and relatlimab in patients with metastatic or locally advanced microsatellite stable (MSS) colorectal cancer.

Enrollment: 59 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Age ≥18 years.
• ECOG performance status 0 or 1
• Have metastatic or locally advanced microsatellite stable (MSS) colorectal adenocarcinoma.
• Cohort A: Primary lesion has a composite PD-L1/Mucin (CPM) score ≥ 15%.
• Cohort B: Primary lesion has a composite PD-L1/Mucin (CPM) score < 15%.
• Cohort C: Prior surgical resection of primary tumor. Prospective biomarker evaluation not required.
• Must have received at least one chemotherapy regimen.
• Patients with the presence of at least one measurable lesion using RECIST 1.1.
• Patients must have available archival tissue from the surgical resection of their primary tumor.
• Patient's acceptance of tumor biopsies.
• Life expectancy of greater than 3 months.
• Patients must have adequate organ and marrow function defined by study - specified laboratory tests.
• Documented LVEF ≥ 50% - 6 month prior to drug administration.
• Must use acceptable form of birth control while on study.
• Ability to understand and willingness to sign a written informed consent document.

Exclusion criteria

• Known history or evidence of brain metastases. Patients with previously treated brain metastases may participate if they are stable for 4 weeks prior to beginning treatment, have no new or enlarging brain metastases, and are not using steroids for at least 1 week prior to initiation of study treatment.
• Require any antineoplastic therapy.
• History of prior treatment with anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4, or anti-Lag-3 antibodies.
• Had chemotherapy, radiation, or steroids within 14 days prior to study treatment.
• Had any cytotoxic drug within 4 weeks prior to initiation of study treatment.
• Hypersensitivity reaction to any monoclonal antibody.
• Has uncontrolled intercurrent acute or chronic medical illness.
• Has an active known or suspected autoimmune disease.
• Has a diagnosis of immunodeficiency.
• Prior tissue or organ allograft or allogeneic bone marrow transplantation.
• Requires daily supplemental oxygen
• History of interstitial lung disease.
• Requires daily supplemental oxygen.
• Significant heart disease
• History of encephalitis, meningitis, or uncontrolled seizures in the year prior to informed consent.
• Infection with HIV or hepatitis B or C at screening.
• Has an active infection.
• Unable to have blood drawn.
• Patient with uncontrolled intercurrent illness including, but not limited to, uncontrolled infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Woman who are pregnant or breastfeeding.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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59 participants in 3 patient groups

Cohort A/B: Nivolumab and Relatlimab

Experimental group

Description:

480mg/160mg (co-administered)

Treatment:

Drug: Relatlimab

Drug: Nivolumab

Drug: Nivolumab

Drug: Relatlimab

Cohort C: Nivolumab and Relatlimab

Experimental group

Description:

480mg/ 960mg or 480mg/480mg (sequential administration)

Treatment:

Drug: Relatlimab

Drug: Nivolumab

Drug: Nivolumab

Drug: Relatlimab

Cohort C: Nivolumab and Relatlimab (co-administration)

Experimental group

Description:

480mg/160mg (co-administration)

Treatment:

Drug: Relatlimab

Drug: Nivolumab

Drug: Nivolumab

Drug: Relatlimab