Colorectal Adenocarcinoma, Microsatellite Stable (MSS) Colorectal Adenocarcinomas
Conditions
Keywords
Relatlimab, Nivolumab, Immunotherapy, Anti-PD-1, Anti-LAG-3, Antibody, MSS, PD-L1, Microsatellite stability, Colorectal cancer, Colon cancer, Rectal cancer
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.
Interventions
DRUGNivolumab
Nivolumab was administered IV on day 1 of each 28 day cycle.
DRUGRelatlimab
Relatlimab was administered IV on day 1 of each 28 day cycle.
Sponsors
Bristol-Myers Squibb
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) | 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
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Experiencing Drug-Related Adverse Events (AEs) Requiring Treatment Discontinuation | 12 months | Defined using NCI CTCAE v5.0 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Cohort A: Composite PD-L1/Mucin (CPM) Positive Colorectal Cancer Participants received 480mg Nivolumab and 160mg Relatlimab on day 1 of each 28 day cycle. | 12 |
| Cohort B: Composite PD-L1/Mucin (CPM) Negative Colorectal Cancer Participants received 480mg Nivolumab and 160mg Relatlimab on day 1 of each 28 day cycle. | 15 |
| Cohort C: Colorectal Cancer With no Biomarker Evaluation Required Participants received 480mg Nivolumab and 960mg Relatlimab (dose reduced to 480mg or 160mg) on day 1 of each 28 day cycle. | 32 |
| Total | 59 |
Baseline characteristics
| Characteristic | Cohort A: Composite PD-L1/Mucin (CPM) Positive Colorectal Cancer | Cohort B: Composite PD-L1/Mucin (CPM) Negative Colorectal Cancer | Cohort C: Colorectal Cancer With no Biomarker Evaluation Required | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 3 Participants | 4 Participants | 8 Participants |
| Age, Categorical Between 18 and 65 years | 11 Participants | 12 Participants | 28 Participants | 51 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 2 Participants | 0 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 11 Participants | 13 Participants | 32 Participants | 56 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 4 Participants | 9 Participants | 16 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) White | 8 Participants | 9 Participants | 21 Participants | 38 Participants |
| Sex: Female, Male Female | 4 Participants | 9 Participants | 17 Participants | 30 Participants |
| Sex: Female, Male Male | 8 Participants | 6 Participants | 15 Participants | 29 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 12 / 12 | 15 / 15 | 26 / 32 |
| other Total, other adverse events | 12 / 12 | 15 / 15 | 32 / 32 |
| serious Total, serious adverse events | 6 / 12 | 12 / 15 | 11 / 32 |
Outcome results
Primary
Objective Response Rate (ORR)
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.
Time frame: 12 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort A: Composite PD-L1/Mucin (CPM) Positive Colorectal Cancer | Objective Response Rate (ORR) | 0 Participants |
| Cohort B: Composite PD-L1/Mucin (CPM) Negative Colorectal Cancer | Objective Response Rate (ORR) | 1 Participants |
| Cohort C: Colorectal Cancer With no Biomarker Evaluation Required | Objective Response Rate (ORR) | 2 Participants |
Secondary
Number of Participants Experiencing Drug-Related Adverse Events (AEs) Requiring Treatment Discontinuation
Defined using NCI CTCAE v5.0
Time frame: 12 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort A: Composite PD-L1/Mucin (CPM) Positive Colorectal Cancer | Number of Participants Experiencing Drug-Related Adverse Events (AEs) Requiring Treatment Discontinuation | 0 Participants |
| Cohort B: Composite PD-L1/Mucin (CPM) Negative Colorectal Cancer | Number of Participants Experiencing Drug-Related Adverse Events (AEs) Requiring Treatment Discontinuation | 0 Participants |
| Cohort C: Colorectal Cancer With no Biomarker Evaluation Required | Number of Participants Experiencing Drug-Related Adverse Events (AEs) Requiring Treatment Discontinuation | 0 Participants |