A Study of Nivolumab-relatlimab Fixed-dose Combination Versus Regorafenib or TAS-102 in Participants With Later-lines of Metastatic Colorectal Cancer
Clinicaltrials.gov identifier recruitment status First Posted Last update posted
NCT05328908 Recruiting April 14, 2022 July 29, 2022

study description
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 late-line microsatellite stable (MSS) metastatic colorectal cancer (mCRC) participants who failed at least 1 but no more than 4 prior lines of therapy for metastatic disease.

Condition or Disease: Colorectal Neoplasms
Intervention/treatment: Drug: Nivolumab-relatlimab FDC
Drug: Regorafenib
Drug: TAS-102
Phase: Phase 3
Detailed Description

N/A


study design
Study Type: Interventional
Estimated Enrollment : 700 participants
Allocation : Randomized
Intervention Model : Parallel Assignment
Masking: None (Open Label) ()
Primary Purpose: Treatment
Official Title: A Study of Nivolumab-relatlimab Fixed-dose Combination Versus Regorafenib or TAS-102 in Participants With Later-lines of Metastatic Colorectal Cancer
Actual Study Start Date: April 2022
Estimated Primary Completion Date: January 2025
Estimated Study Completion Date: May 2028

Arms and interventions
Arm Intervention/treatment
Experimental: Arm A: Nivolumab + Relatlimab Fixed-dose Combination (FDC)
Drug: Nivolumab-relatlimab FDC
Specified dose on specified days
Active Comparator: Arm B: Investigator's Choice
Treatment with Regorafenib or TAS-102
Drug: Regorafenib
Specified dose on specified days

Drug: TAS-102
Specified dose on specified days
outcome measures
Primary Outcome Measures: 1. Overall survival (OS) in randomized participants with programmed death-ligand 1 (PD-L1) combined positive score (CPS) ≥ 1 [ Time Frame: Up to 5 years after last participant randomized ]
2. OS in all randomized participants [ Time Frame: Up to 5 years after last participant randomized ]
Secondary Outcome Measures: 1. Objective response rate (ORR) by Blinded Independent Central Review (BICR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 in randomized participants with PD-L1 CPS ≥ 1 [ Time Frame: Up to 5 years after last participant randomized ]
2. ORR by BICR per RECIST v1.1 in all randomized participants [ Time Frame: Up to 5 years after last participant randomized ]
3. Progression-free survival (PFS) by BICR per RECIST v1.1 in randomized participants with PD-L1 CPS ≥ 1 [ Time Frame: Up to 5 years after last participant randomized ]
4. PFS by BICR per RECIST v1.1 in all randomized participants [ Time Frame: Up to 5 years after last participant randomized ]
5. Duration of response (DoR) by BICR per RECIST v1.1 in responders with PD-L1 CPS ≥ 1 [ Time Frame: Up to 5 years after last participant randomized ]
6. DoR by BICR per RECIST v1.1 in all responders [ Time Frame: Up to 5 years after last participant randomized ]
7. Number of participants with adverse events (AEs) [ Time Frame: Up to 135 days after participant's last dose ]
8. Number of participants with serious adverse events (SAEs) [ Time Frame: Up to 135 days after participant's last dose ]
9. Number of participants with immune-mediated adverse events (IMAEs) [ Time Frame: Up to 135 days after participant's last dose ]
10. Number of participants with AEs leading to discontinuation [ Time Frame: Up to 135 day's after participant's last dose ]
11. Number of participants with clinical laboratory abnormalities [ Time Frame: Up to 135 days after participant's last dose ]
12. DeFS-QoL: The time from randomization to death or at least a 15-points worsening from baseline in the EORTC QLQ-C30 GHS/QoL scale, with no subsequent improvement above the 15-point worsening from baseline score [ Time Frame: Up to 5 years after last participant randomized ]
DeFS-QoL = Deterioration Free Survival-Quality of Life. The EORTC (European Organisation for Research and Treatment of Cancer) Quality of Life Questionnaire-Core 30 (QLQ-C30) consists of 30 questions incorporated into 5 functional scales (physical, role, cognitive, emotional, and social functioning), 3 multi-item symptom scales (fatigue, pain, nausea and vomiting), a global health status / Quality of Life scale, and six single symptom items. All of the scale and single-item measures range in score from 0 to 100, where a higher score represents a higher response level. High functional scores indicates more favorable outcomes and a higher score on the symptom domains indicates higher symptom burden/less favorable patient outcome.
13. DeFS-PF: The time from randomization to death or at least a 10-points worsening from baseline in the EORTC QLQ-C30 physical function scale, with no subsequent improvement above the 10-point worsening from baseline score [ Time Frame: Up to 5 years after last participant randomized ]
DeFS-PF = Deterioration Free Survival-Physical Function. The EORTC (European Organisation for Research and Treatment of Cancer) Quality of Life Questionnaire-Core 30 (QLQ-C30) consists of 30 questions incorporated into 5 functional scales (physical, role, cognitive, emotional, and social functioning), 3 multi-item symptom scales (fatigue, pain, nausea and vomiting), a global health status / Quality of Life scale, and six single symptom items. All of the scale and single-item measures range in score from 0 to 100, where a higher score represents a higher response level. High functional scores indicates more favorable outcomes and a higher score on the symptom domains indicates higher symptom burden/less favorable patient outcome.

Eligibility Criteria
Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
Sexes Eligible for Study: All
Accepts Healthy Volunteers: No
Criteria

Inclusion Criteria:

Histological confirmed previously treated colorectal cancer with adenocarcinoma histology with metastatic or recurrent unresectable disease at study entry Must have historically or locally confirmed tumor microsatellite stability (stable) (MSS) / proficient mismatch repair (pMMR) status

Participants must have:

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), which must include a fluoropyrimidine, oxaliplatin, irinotecan, an anti-VEGF therapy, and anti-EGFR therapy (if KRAS wild-type), if approved in the respective country, or; 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

Other protocol-defined inclusion/exclusion criteria apply


Contacts and Locations
Contacts

Contact: BMS Study Connect Contact Center www.BMSStudyConnect.com 855-907-3286 Clinical.Trials@bms.com

Contact: First line of the email MUST contain NCT # and Site #.

Locations
United States, Arkansas Local Institution Rogers
United States, California City Of Hope Duarte
United States, California Local Institution Los Angeles
United States, Connecticut Eastern Connecticut Hematology And Oncology Associates Norwich
United States, Florida Local Institution Miami
United States, Georgia Northside Hospital Atlanta
United States, Idaho Local Institution Boise
United States, Illinois Local Institution Chicago
United States, Indiana Fort Wayne Medical Oncology & Hematology Fort Wayne
United States, Michigan Local Institution Ann Arbor
United States, Minnesota Mayo Clinic in Arizona - Phoenix Rochester
United States, New Jersey Astera Cancer Care East Brunswick
United States, North Carolina Local Institution Durham
United States, Ohio Local Institution Cincinnati
United States, Ohio Local Institution Columbus
United States, Ohio Local Institution Columbus
United States, Pennsylvania Local Institution Philadelphia
United States, South Carolina Charleston Hematology Oncology Associates CHOA Charleston
United States, South Dakota Local Institution Sioux Falls
United States, Texas The Center For Cancer And Blood Disorders Fort Worth
United States, Wisconsin Local Institution Madison
Argentina, Buenos Aires Local Institution - 0022 Ciudad Autonoma Buenos Aires
Argentina, Buenos Aires Local Institution Ciudad Autónoma Buenos Aires
Argentina, RIO Negro Local Institution Viedma
Argentina Local Institution Buenos Aires
Argentina Local Institution Buenos Aires
Australia, New South Wales Local Institution Wagga Wagga
Australia, New South Wales Local Institution Westmead
Australia, Queensland Local Institution - 0001 Greenslopes Qld
Australia, South Australia Local Institution - 0002 Woodville South
Australia, Victoria Local Institution - 0010 Clayton
Australia, Victoria Local Institution Melbourne
Australia, Western Australia Local Institution - 0027 Perth
Austria Local Institution Graz
Austria Local Institution Klagenfurt
Belgium Local Institution Edegem
Belgium Local Institution Gent
Belgium Local Institution Leuven
Belgium Local Institution Woluwé-Saint-Lambert
Canada, Alberta Local Institution Edmonton
Canada, Ontario Local Institution Ottawa
Canada, Ontario Local Institution Toronto
Canada, Quebec Local Institution Montreal
Canada, Quebec Local Institution Montreal
Canada, Quebec Local Institution Sherbrooke
Chile, Metropolitana Local Institution Santiago
Chile, Metropolitana Local Institution Santiago
China, Beijing Local Institution - 0122 Beijing
China, Hunan Local Institution - 0125 Changsha
Czechia Local Institution Horovice
Czechia Local Institution Hradec Kralove
Czechia Local Institution Olomouc
Czechia Local Institution Prague 5
France Local Institution Bordeaux
France Local Institution Caen
France Local Institution Dijon
France Local Institution Levallois-Perret
France Local Institution Lyon
France Local Institution Paris cedex 12
France Local Institution Suresnes
Germany Local Institution Berlin
Germany Local Institution Essen
Germany Local Institution Frankfurt A. Main
Germany Local Institution Hamburg
Germany Local Institution Mannheim
Germany Local Institution Muenchen
Germany Local Institution Reutlingen
Germany Local Institution Wuerzburg
Italy Local Institution Catania
Italy Local Institution Genova
Italy Local Institution Milano
Italy Local Institution Milano
Italy Local Institution Napoli
Italy Local Institution Napoli
Italy Local Institution - 0136 Padova
Italy Local Institution Reggio Emilia
Japan, Chiba Local Institution Chiba-shi
Japan, Chiba Local Institution Kashiwa-shi
Japan, Ehime Local Institution Matsuyama-shi
Japan, Hokkaido Local Institution Sapporo-shi
Japan, Kanagawa Local Institution Kawasaki-shi
Japan, Osaka Local Institution Suita-shi
Japan, Saitama Local Institution Hidaka-Shi
Japan, Saitama Local Institution Kitaadachi-gun
Japan, Shizuoka Local Institution Sunto-gun
Japan, Tokyo Local Institution Chuo-ku
Japan, Tokyo Local Institution - 0108 Koto-ku
Japan Local Institution Osaka
Korea, Republic of Local Institution Goyangsi Ilsandonggu
Korea, Republic of Local Institution Seoul
Korea, Republic of Local Institution Seoul
Korea, Republic of Local Institution Seoul
Korea, Republic of Local Institution Songpa-gu, Seoul
Netherlands Local Institution Amsterdam
Netherlands Local Institution Utrecht
Poland Local Institution Krakow
Poland Local Institution Warszawa
Poland Local Institution Warszawa
Poland Local Institution Warszawa
Puerto Rico Local Institution - 0106 San Juan
Singapore Local Institution Singapore
Singapore Local Institution Singapore
Spain Local Institution A Coruña
Spain Local Institution Badalona
Spain Local Institution Barcelona
Spain Local Institution Barcelona
Spain Local Institution Madrid
Spain Local Institution Madrid
Spain Local Institution Sevilla
Spain Local Institution Zaragoza
Sweden Local Institution Goteborg
Sweden Local Institution Malmo
Sweden Local Institution Stockholm
Sweden Local Institution Uppsala
Switzerland Local Institution Aarau
Switzerland Local Institution Bern
Taiwan Local Institution Kao-Hsiung
Taiwan Local Institution Tainan
Taiwan Local Institution Tainan
Sponsors and Collaborators
Bristol-Myers Squibb
Investigator
Study Director : Bristol-Myers Squibb Bristol-Myers Squibb
More Information
Responsible Party : Bristol-Myers Squibb
ClinicalTrials.gov Identifier : NCT05328908     
Other Study ID Numbers : CA224-123, 2021-004285-35
First Posted : April 14, 2022
Last Update Posted : July 29, 2022
Last Verified : July 2022
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Bristol-Myers Squibb: Regorafenib
Relatlimab
Nivolumab
Micro-satellite Stable (MSS) Metastatic Colorectal Cancer (mCRC)
BMS-986213
Stivarga
Lonsurf
Additional relevant MeSH terms :
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Colorectal Neoplasms