Phase A Phase 2 Study Evaluating Response and Biomarkers in Patients With Microsatellite Stable (MSS) Advanced Colorectal Cancer Treated With Nivolumab in Combination With Relatlimab
Overview
- Phase
- Phase 2
- Intervention
- Nivolumab
- Conditions
- Microsatellite Stable (MSS) Colorectal Adenocarcinomas
- Sponsor
- Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
- Enrollment
- 59
- Locations
- 1
- Primary Endpoint
- Objective Response Rate (ORR)
- Status
- Completed
- Last Updated
- 10 months ago
Overview
Brief Summary
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.
Investigators
Eligibility Criteria
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.
- •Patients must have available archival tissue from the surgical resection of their primary tumor.
- •Patient's acceptance of tumor biopsies.
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.
Arms & Interventions
Cohort A: Composite PD-L1/Mucin (CPM) positive colorectal cancer
Participants were pre-screened for CPM score. The CPM score integrates the percent of PD-L1 expression at the tumor interface and the percent of acellular mucin in the tumor area (\[%PD-L1 + % acellular mucin\]/2) using each participant's primary tumor tissue. A CPM score cutoff of greater than or equal to 15% was used to determine CPM positivity. Participants received 480mg Nivolumab and 160mg Relatlimab.
Intervention: Nivolumab
Cohort A: Composite PD-L1/Mucin (CPM) positive colorectal cancer
Participants were pre-screened for CPM score. The CPM score integrates the percent of PD-L1 expression at the tumor interface and the percent of acellular mucin in the tumor area (\[%PD-L1 + % acellular mucin\]/2) using each participant's primary tumor tissue. A CPM score cutoff of greater than or equal to 15% was used to determine CPM positivity. Participants received 480mg Nivolumab and 160mg Relatlimab.
Intervention: Relatlimab
Cohort B: Composite PD-L1/Mucin (CPM) negative colorectal cancer
Participants were pre-screened for CPM score. The CPM score integrates the percent of PD-L1 expression at the tumor interface and the percent of acellular mucin in the tumor area (\[%PD-L1 + % acellular mucin\]/2) using each participant's primary tumor tissue. A CPM score cutoff of less than 15% was used to determine CPM negativity. Participants received 480mg Nivolumab and 160mg Relatlimab.
Intervention: Nivolumab
Cohort B: Composite PD-L1/Mucin (CPM) negative colorectal cancer
Participants were pre-screened for CPM score. The CPM score integrates the percent of PD-L1 expression at the tumor interface and the percent of acellular mucin in the tumor area (\[%PD-L1 + % acellular mucin\]/2) using each participant's primary tumor tissue. A CPM score cutoff of less than 15% was used to determine CPM negativity. Participants received 480mg Nivolumab and 160mg Relatlimab.
Intervention: Relatlimab
Cohort C: Colorectal cancer with no biomarker evaluation required
Participants were not pre-screened for composite PD-L1/mucin (CPM) score. Participants received 480mg Nivolumab and 960mg Relatlimab (dose reduced to 480mg or 160mg).
Intervention: Nivolumab
Cohort C: Colorectal cancer with no biomarker evaluation required
Participants were not pre-screened for composite PD-L1/mucin (CPM) score. Participants received 480mg Nivolumab and 960mg Relatlimab (dose reduced to 480mg or 160mg).
Intervention: Relatlimab
Outcomes
Primary Outcomes
Objective Response Rate (ORR)
Time Frame: 12 months
ORR is defined as the number of patients achieving a complete response (CR) or partial response (PR) based on RECIST 1.1 criteria. CR = disappearance of all target lesions, PR is =\>30% decrease in sum of diameters of target lesions. Participants who discontinue due to toxicity or clinical progression prior to post-baseline tumor assessments will be considered as non-responders. Participants who discontinue for other reasons prior to their first dose of study drug will not included in the analysis.
Secondary Outcomes
- Number of Participants Experiencing Drug-Related Adverse Events (AEs) Requiring Treatment Discontinuation(12 months)