Colorectal Neoplasms
Conditions
Keywords
Micro-satellite Stable (MSS) Metastatic Colorectal Cancer (mCRC), Relatlimab, Nivolumab, BMS-986213, Regorafenib, Stivarga, Lonsurf
Brief summary
The purpose of this study is to evaluate relatlimab in combination with nivolumab, administered as a fixed-dose combination (nivolumab-relatlimab FDC, also referred to as BMS-986213) for the treatment of non-microsatellite instability high (MSI-H)/deficient mismatch repair (dMMR) metastatic colorectal cancer (mCRC) participants who failed at least 1 but no more than 4 prior lines of therapy for metastatic disease.
Interventions
DRUGNivolumab-relatlimab FDC
Specified dose on specified days
DRUGRegorafenib
Specified dose on specified days
DRUGTAS-102
Specified dose on specified days
Sponsors
Bristol-Myers Squibb
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histological confirmed previously treated colorectal cancer with adenocarcinoma histology with metastatic or recurrent unresectable disease at study entry. * Participants must have:. i) progressed during or within approximately 3 months following the last administration of approved standard therapies (at least 1, but not more than 4 prior lines of therapies in the metastatic setting), which must include a fluoropyrimidine, oxaliplatin, irinotecan, an anti-VEGF therapy, and anti-EGFR therapy (if RAS wild-type), if available in the respective country, or;. ii) been intolerant to prior systemic chemotherapy regimens if there is documented evidence of clinically significant intolerance despite adequate supportive measures. * Must have sufficient tumor tissue \& evaluable PD-L1 expression to meet the study requirements. * Must have measurable disease per RECIST v1.1. Participants with lesions in a previously irradiated field as the sole site of measurable disease will be permitted to enroll provided the lesion(s) have demonstrated clear progression and can be measured accurately.
Exclusion criteria
* Prior treatment with either an immunotherapy or with regorafenib or with TAS-102. * Untreated central nervous system (CNS) metastases, participants are eligible if CNS metastases have been treated and participants have neurologically returned to baseline (except for residual signs or symptoms related to the CNS treatment). * History of refractory hypertension not controlled with anti-hypertensive therapy, myocarditis (regardless of etiology), uncontrolled arrhythmias, acute coronary syndrome within 6 months prior to dosing, Class II congestive heart failure (as per the New York Heart Association Functional Classification), interstitial lung disease/pneumonitis or an active, known or suspected autoimmune disease. * Confirmed tumor microsatellite instable high/deficient mismatch repair (MSI-H/dMMR) status as per local standard testing; MSI/MMR test results from initial diagnosis are acceptable. * Other protocol-defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | From date of randomization to the date of death due to any cause (Up to approxaimtely 38 months) | OS is defined as the time from date of randomization to the date of death due to any cause. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) Per Blinded Independent Central Review (BICR) | From randomization until the date of objectively documented response (Up to approximately 38 months) | ORR is defined as the percent of participants with a best overall response (BOR) of confirmed Complete Response (CR) or Partial Response (PR). CR=Disappearance of all target lesions. PR=At least a 30% decrease in the sum of diameters of target lesions. |
| Progression Free Survival (PFS) Per Blinded Independent Central Review (BICR) | From date of randomization to the date of first documented progression or death, whichever occurs first (Up to approximately 38 months) | PFS is defined as the time from randomization to first documented progression (PD) or death due to any cause, whichever is earlier. PD=At least a 20% increase in the sum of diameters of target lesions. |
| Duration of Response (DoR) Per Blinded Independent Central Review (BICR) | From date of randomization to the date of first documented progression or death, whichever occurs first (Up to approximately 38 months) | DoR is defined as the time between the date of first confirmed documented response (CR or PR) to the date of the first documented tumor progression as determined by BICR (per RECIST v1.1 criteria), or death due to any cause, whichever occurs first. CR=Disappearance of all target lesions. PR=At least a 30% decrease in the sum of diameters of target lesions. PD=At least a 20% increase in the sum of diameters of target lesions. |
| Number of Participants With Adverse Events (AEs) | From first dose until 30 days post last dose (Up to 24 months) | AE is defined as any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product; it does not necessarily have to have a causal relationship with this treatment. An SAE is defined as any untoward medical occurrence at any dose that: results in death, is immediately life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability or incapacity or substantial disruption of the ability to conduct normal life functions, results in a congenital abnormality or birth defect, or is an important medical event that may not result in death, be life-threatening, or require hospitalization, but may require medical or surgical intervention to prevent any of the outcomes listed above. |
| Number of Participants With Select Adverse Events (AEs) | From first dose until 30 days post last dose (Up to 24 months) | AE is defined as any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product; it does not necessarily have to have a causal relationship with this treatment. |
| Number of Participants With Immune Mediated Adverse Events (IMAEs) | From first dose until 30 days post last dose (Up to 24 months) | AE is defined as any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product; it does not necessarily have to have a causal relationship with this treatment. |
| Number of Participants With Laboratory Test Results of Worst Toxicity Grade 3 and 4 | From first dose until 30 days post last dose (Up to 24 months) | Blood samples were collected for assessment of laboratory test results. All abnormalities were graded as per CTCAE v5.0 on a scale from 1 to 4, with Grade 1 being mild and asymptomatic; Grade 2 is moderate requiring minimal, local or noninvasive intervention; Grade 3 is severe or medically significant but not immediately life-threatening; Grade 4 events are usually severe enough to require hospitalization. |
| Time Until Definitive Deterioration - Quality of Life (TUDD-QoL) | From randomization until the first date of a definititve clincial decline from baseline in QoL scale score (Up to approximately 38 months) | TUDD-QoL is defined as time from randomization until the first date of a definitive clinically meaningful decline from baseline in EORTC QLQ-C30 health status/QoL scale score. A definitive deterioration is defined as when all subsequent PRO assessments after a deterioration also reach or exceed the pre-defined meaningful change threshold. A decrease in score of at least 15 points from baseline will be considered to be the meaningful change threshold (MCT) for the global health status/quality-of-life and scale. |
| Time Until Definitive Deterioration - Physical Function (TUDD-PF) | From randomization until the first date of a definititve clincial decline from baseline in PF scale score (Up to approximately 38 months) | TUDD-PF is defined as time from randomization until the first date of a definitive clinically meaningful decline from baseline in EORTC QLQ-C30 physical function scale score. A definitive deterioration is defined as when all subsequent PRO assessments after a deterioration also reach or exceed the pre-defined meaningful change threshold. A 10-point decrease from baseline will be considered the meaning change threshold (MCT) for the physical function scale. |
| Progression Free Survival (PFS) Per Investigator | From date of randomization to the date of first documented progression or death, whichever occurs first (Up to approximately 38 months) | PFS is defined as the time from randomization to first documented progression (PD) or death due to any cause, whichever is earlier. PD=At least a 20% increase in the sum of diameters of target lesions. |
| Objective Response Rate (ORR) Per Investigator | From randomization until the date of objectively documented response (Up to approximately 38 months) | ORR is defined as the percent of participants with a best overall response (BOR) of confirmed Complete Response (CR) or Partial Response (PR). CR=Disappearance of all target lesions. PR=At least a 30% decrease in the sum of diameters of target lesions. |
| Duration of Response (DoR) Per Investigator | From date of randomization to the date of first documented progression or death, whichever occurs first (Up to approximately 38 months) | DoR is defined as the time between the date of first confirmed documented response (CR or PR) to the date of the first documented tumor progression as determined by BICR (per RECIST v1.1 criteria), or death due to any cause, whichever occurs first. CR=Disappearance of all target lesions. PR=At least a 30% decrease in the sum of diameters of target lesions. PD=At least a 20% increase in the sum of diameters of target lesions. |
Countries
Argentina, Australia, Austria, Belgium, Canada, Chile, China, Czechia, France, Germany, Italy, Japan, Netherlands, Poland, Puerto Rico, Singapore, South Korea, Spain, Sweden, Switzerland, Taiwan, United States
Contacts
STUDY_DIRECTORBristol-Myers Squibb
Bristol-Myers Squibb
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 58.7 Years STANDARD_DEVIATION 11.2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 18 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 323 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 83 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants |
| Race (NIH/OMB) Asian | 257 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 36 Participants |
| Race (NIH/OMB) White | 424 Participants |
| Sex: Female, Male Female | 340 Participants |
| Sex: Female, Male Male | 209 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 292 / 385 | 304 / 384 |
| other Total, other adverse events | 333 / 383 | 323 / 358 |
| serious Total, serious adverse events | 227 / 383 | 195 / 358 |
Outcome results
None listed