A Study of Nivolumab-relatlimab Fixed-dose Combination Versus Regorafenib or TAS-102 in Participants With Later-lines of Metastatic Colorectal Cancer (RELATIVITY-123)

A Phase 3, Randomized, Open-label Study of Relatlimab-nivolumab Fixed-dose Combination Versus Regorafenib or Trifluridine + Tipiracil (TAS-102) for Participants With Later-lines of Metastatic Colorectal Cancer

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.

Study Overview

• Status: Terminated
• Conditions: Colorectal Neoplasms
• Intervention / Treatment: Drug: Regorafenib; Drug: Nivolumab-relatlimab FDC; Drug: TAS-102

• Study Type: Interventional
• Enrollment (Actual): 769
• Phase: Phase 3

Expanded Access

No longer available outside the clinical trial. See expanded access record.

Contacts and Locations

Study Locations

• Argentina
  • Ciudad Autónoma Buenos Aires, Argentina, 1834
    • Local Institution - 0024
  • Rio Grande, Argentina, 8500
    • Local Institution - 0023
  • B
    • Ciudad Autónoma Buenos Aires, B, Argentina, C1181ACH
      • Local Institution - 0026
  • Buenos Aires
    • Ciudad Autónoma Buenos Aires, Buenos Aires, Argentina, 1425
      • Local Institution - 0022
• Australia
  • New South Wales
    • Wagga Wagga, New South Wales, Australia, 2650
      • Local Institution - 0098
    • Westmead, New South Wales, Australia, 2145
      • Local Institution - 0114
  • Queensland
    • Greenslopes, Queensland, Australia, 4120
      • Local Institution - 0001
  • Victoria
    • Clayton, Victoria, Australia, 3168
      • Local Institution - 0010
    • Melbourne, Victoria, Australia, 3084
      • Local Institution - 0021
  • Western Australia
    • Murdoch, Western Australia, Australia, 6150
      • Local Institution - 0027
• Austria
  • Graz, Austria, 6800
    • Local Institution - 0030
  • Klagenfurt, Austria, 9020
    • Local Institution - 0078
  • Salzburg, Austria, 5020
    • Local Institution - 0131
• Belgium
  • Edegem, Belgium, 2650
    • Local Institution - 0070
  • Leuven, Belgium, 3000
    • Local Institution - 0120
  • BRU
    • Woluwé-Saint-Lambert, BRU, Belgium, 1200
      • Local Institution - 0062
  • VOV
    • Ghent, VOV, Belgium, 9000
      • Local Institution - 0068
• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 1Z2
      • Local Institution - 0003
  • Ontario
    • Ottawa, Ontario, Canada, K1H 8L6
      • Local Institution - 0014
    • Toronto, Ontario, Canada, M5G 2M9
      • Local Institution - 0007
  • Quebec
    • Montreal, Quebec, Canada, H2X 3E4
      • Local Institution - 0019
    • Montreal, Quebec, Canada, H4A 3J1
      • Local Institution - 0104
    • Sherbrooke, Quebec, Canada, J1H 5N4
      • Local Institution - 0004
• Chile
  • RM
    • Santiago, RM, Chile, 7560908
      • Local Institution - 0015
    • Santiago, RM, Chile, 8380456
      • Local Institution - 0033
• China
  • Beijing, China, 100142
    • Local Institution - 0122
  • Hangzhou, China, 310003
    • Local Institution - 0139
  • Shanghai, China, 200032
    • Local Institution - 0153
  • Shenyang, China, 110042
    • Local Institution - 0149
  • CQ
    • Chongqing, CQ, China, 400030
      • Local Institution - 0134
  • Guangdong
    • Guangzhou, Guangdong, China, 510655
      • Local Institution - 0151
  • HB
    • Wuhan, HB, China, 430071
      • Local Institution - 0126
  • HN
    • Changsha, HN, China, 410013
      • Local Institution - 0138
  • Hubei
    • Wuhan, Hubei, China, 430079
      • Local Institution - 0164
  • Hunan
    • Changsha, Hunan, China, 410013
      • Local Institution - 0158
  • JS
    • Nanjing, JS, China, 210008
      • Local Institution - 0143
  • Jiangsu
    • Huaian, Jiangsu, China, 223300
      • Local Institution - 0146
  • SD
    • Jinan, SD, China, 250117
      • Local Institution - 0142
  • SHA
    • Xi'an, SHA, China, 710038
      • Local Institution - 0152
  • SX
    • Taiyuan, SX, China, 030013
      • Local Institution - 0141
  • Sichuan
    • Chengdu, Sichuan, China, 610041
      • Local Institution - 0144
  • TJ
    • Tianjin, TJ, China, 300121
      • Local Institution - 0150
  • ZJ
    • Hangzhou, ZJ, China, 310022
      • Local Institution - 0160
• Czechia
  • Hořovice, Czechia, 26801
    • Local Institution - 0099
  • Hradec Králové, Czechia, 500 05
    • Local Institution - 0016
  • Olomouc, Czechia, 775 20
    • Local Institution - 0100
  • Ostrava, Czechia, 708 52
    • Local Institution - 0123
  • Prague, Czechia, 150 06
    • Local Institution - 0064
• France
  • Bordeaux, France, 33000
    • Local Institution - 0066
  • Dijon, France, 21000
    • Local Institution - 0090
  • Levallois-Perret, France, 92300
    • Local Institution - 0020
  • Lyon, France, 69008
    • Local Institution - 0036
  • Paris, France, 75012
    • Local Institution - 0089
  • Suresnes, France, 92151
    • Local Institution - 0039
  • Caen
    • Caen, Caen, France, 14000
      • Local Institution - 0017
• Germany
  • Hamburg, Germany, 20249
    • Local Institution - 0040
  • München, Germany, 81377
    • Local Institution - 0034
  • Baden-Wurttemberg
    • Mannheim, Baden-Wurttemberg, Germany, 68167
      • Local Institution - 0054
    • Reutlingen, Baden-Wurttemberg, Germany, 72764
      • Local Institution - 0056
  • Bavaria
    • Würzburg, Bavaria, Germany, 97080
      • Local Institution - 0053
  • Hesse
    • Frankfurt A. Main, Hesse, Germany, 60488
      • Local Institution - 0041
  • North Rhine-Westphalia
    • Essen, North Rhine-Westphalia, Germany, 45147
      • Local Institution - 0101
  • State of Berlin
    • Berlin, State of Berlin, Germany, 13353
      • Local Institution - 0055
• Italy
  • Catania, Italy, 95122
    • Local Institution - 0060
  • Genova, Italy, 16132
    • Local Institution - 0091
  • Milan, Italy, 20133
    • Local Institution - 0045
  • Naples, Italy, 80131
    • Local Institution - 0115
  • Naples, Italy, 80138
    • Local Institution - 0061
  • MI
    • Milan, MI, Italy, 20162
      • Local Institution - 0046
  • PD
    • Padova, PD, Italy, 35128
      • Local Institution - 0148
  • RE
    • Reggio Emilia, RE, Italy, 42123
      • Local Institution - 0059
• Japan
  • Chiba, Japan, 260-8717
    • Local Institution - 0107
  • Chūōku, Japan, 104-0045
    • Local Institution - 0103
  • Hidaka-shi, Japan, 350-1298
    • Local Institution - 0105
  • Kasama-Shi, Japan, 309-1793
    • Local Institution - 0154
  • Kashiwa-Shi, Japan, 277-8577
    • Local Institution - 0084
  • Kawasaki-Shi, Japan, 216-8511
    • Local Institution - 0086
  • Kitaadachi-gun, Japan, 362-0806
    • Local Institution - 0119
  • Kōtoku, Japan, 135-8550
    • Local Institution - 0108
  • Matsuyama, Japan, 791-0280
    • Local Institution - 0118
  • Sapporo, Japan, 060-8648
    • Local Institution - 0088
  • Suita-Shi, Japan, 565-0871
    • Local Institution - 0083
  • Sunto-gun, Japan, 411-8777
    • Local Institution - 0085
  • Yokohama, Japan, 241-8515
    • Local Institution - 0124
  • Osaka
    • Osaka, Osaka, Japan, 5418567
      • Local Institution - 0110
• Netherlands
  • Amsterdam, Netherlands, 1066 CX
    • Local Institution - 0050
• Poland
  • Krakow, Poland, 30-727
    • Local Institution - 0018
  • Warsaw, Poland, 02-781
    • Local Institution - 0052
  • Masovian Voivodeship
    • Warsaw, Masovian Voivodeship, Poland, 02-507
      • Local Institution - 0051
  • Pl-mz
    • Warsaw, Pl-mz, Poland, 05-400
      • Local Institution - 0037
• Puerto Rico
  • PR
    • San Juan, PR, Puerto Rico, 00927
      • Local Institution - 0106
• Singapore
  • Singapore, Singapore, 169610
    • Local Institution - 0109
  • Singapore, Singapore, 329563
    • Local Institution - 0087
• South Korea
  • Goyang-si, Gyeonggi-do, South Korea, 10408
    • Local Institution - 0073
  • Seongnamsi Bundanggu, South Korea, 13620
    • Local Institution - 0129
  • Seoul, South Korea, 05505
    • Local Institution - 0092
  • Seoul, South Korea, 06351
    • Local Institution - 0075
  • Seoul, South Korea, 110-744
    • Local Institution - 0074
  • Seoul-teukbyeolsi
    • Seoul, Seoul-teukbyeolsi, South Korea, 03722
      • Local Institution - 0072
• Spain
  • A Coruña, Spain, 15006
    • Local Institution - 0112
  • Barcelona, Spain, 08035
    • Local Institution - 0080
  • Seville, Spain, 41013
    • Local Institution - 0035
  • B
    • Badalona, B, Spain, 08916
      • Local Institution - 0029
    • Barcelona, B, Spain, 08036
      • Local Institution - 0093
  • M
    • Madrid, M, Spain, 28041
      • Local Institution - 0102
  • Madrid
    • Madrid, Madrid, Spain, 28046
      • Local Institution - 0113
  • Z
    • Zaragoza, Z, Spain, 50009
      • Local Institution - 0116
• Sweden
  • Gothenburg, Sweden, 413 45
    • Local Institution - 0067
  • Malmö, Sweden, 214 28
    • Local Institution - 0094
  • AB
    • Stockholm, AB, Sweden, 112 81
      • Local Institution - 0038
    • Stockholm, AB, Sweden, 171 76
      • Local Institution - 0135
  • C
    • Uppsala, C, Sweden, 751 85
      • Local Institution - 0058
• Switzerland
  • Bern, Switzerland, 3010
    • Local Institution - 0069
  • Canton of Aargau
    • Aarau, Canton of Aargau, Switzerland, 5000
      • Local Institution - 0057
• Taiwan
  • Tainan, Taiwan, 70403
    • Local Institution - 0077
  • CHA
    • Changhua, CHA, Taiwan, 500
      • Local Institution - 0128
  • KHH
    • Kaohsiung City, KHH, Taiwan, 83301
      • Local Institution - 0111
  • TNN
    • Tainan, TNN, Taiwan, 704
      • Local Institution - 0076
  • TPE
    • Zhongzheng, TPE, Taiwan, 100
      • Local Institution - 0121
• United States
  • Arkansas
    • Springdale, Arkansas, United States, 72762-5328
      • Local Institution - 0044
  • California
    • Los Angeles, California, United States, 90089-0112
      • Local Institution - 0012
  • Connecticut
    • Norwich, Connecticut, United States, 06360-2753
      • Local Institution - 0117
  • Florida
    • Miami, Florida, United States, 33176
      • Local Institution - 0025
  • Georgia
    • Atlanta, Georgia, United States, 30342
      • Local Institution - 0031
  • Idaho
    • Boise, Idaho, United States, 83712-6267
      • Local Institution - 0071
  • Indiana
    • Fort Wayne, Indiana, United States, 46805
      • Local Institution - 0081
  • Massachusetts
    • Boston, Massachusetts, United States, 02214
      • Massachusetts General Hospital,
  • Michigan
    • Ann Arbor, Michigan, United States, 48109-1382
      • Local Institution - 0042
  • New Jersey
    • East Brunswick, New Jersey, United States, 08816-3340
      • Local Institution - 0043
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Local Institution - 0009
  • Ohio
    • Cincinnati, Ohio, United States, 45220
      • Local Institution - 0082
    • Columbus, Ohio, United States, 43210-1240
      • Local Institution - 0095
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19111-2434
      • Local Institution - 0147
  • South Carolina
    • Charleston, South Carolina, United States, 29414
      • Local Institution - 0008
  • South Dakota
    • Sioux Falls, South Dakota, United States, 57104
      • Local Institution - 0096
  • Tennessee
    • Nashville, Tennessee, United States, 37203-2173
      • Local Institution - 0127
  • Texas
    • Fort Worth, Texas, United States, 76104-4611
      • Local Institution - 0097
  • Virginia
    • Richmond, Virginia, United States, 23284
      • Local Institution - 0132
  • Wisconsin
    • Madison, Wisconsin, United States, 53705-2275
      • Local Institution - 0005

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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/Exclusion criteria apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A: Nivolumab + Relatlimab Fixed-dose Combination (FDC)	Drug: Nivolumab-relatlimab FDC; Specified dose on specified days; Other Names: BMS-986213
Active Comparator: Arm B: Investigator's Choice; Treatment with Regorafenib or TAS-102	Drug: Regorafenib; Specified dose on specified days; Other Names: Stivarga; Drug: TAS-102; Specified dose on specified days; Other Names: Lonsurf; Trifluridine/Tipiracil

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	OS is defined as the time from date of randomization to the date of death due to any cause.	From date of randomization to the date of death due to any cause (Up to approxaimtely 38 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR) Per Blinded Independent Central Review (BICR)	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.	From randomization until the date of objectively documented response (Up to approximately 38 months)
Progression Free Survival (PFS) Per Blinded Independent Central Review (BICR)	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.	From date of randomization to the date of first documented progression or death, whichever occurs first (Up to approximately 38 months)
Duration of Response (DoR) Per Blinded Independent Central Review (BICR)	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.	From date of randomization to the date of first documented progression or death, whichever occurs first (Up to approximately 38 months)
Number of Participants With Adverse Events (AEs)	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.	From first dose until 30 days post last dose (Up to 24 months)
Number of Participants With Select Adverse Events (AEs)	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.	From first dose until 30 days post last dose (Up to 24 months)
Number of Participants With Immune Mediated Adverse Events (IMAEs)	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.	From first dose until 30 days post last dose (Up to 24 months)
Number of Participants With Laboratory Test Results of Worst Toxicity Grade 3 and 4	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.	From first dose until 30 days post last dose (Up to 24 months)
Time Until Definitive Deterioration - Quality of Life (TUDD-QoL)	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.	From randomization until the first date of a definititve clincial decline from baseline in QoL scale score (Up to approximately 38 months)
Time Until Definitive Deterioration - Physical Function (TUDD-PF)	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.	From randomization until the first date of a definititve clincial decline from baseline in PF scale score (Up to approximately 38 months)
Progression Free Survival (PFS) Per Investigator	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.	From date of randomization to the date of first documented progression or death, whichever occurs first (Up to approximately 38 months)
Objective Response Rate (ORR) Per Investigator	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.	From randomization until the date of objectively documented response (Up to approximately 38 months)
Duration of Response (DoR) Per Investigator	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.	From date of randomization to the date of first documented progression or death, whichever occurs first (Up to approximately 38 months)

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb
• Investigators: Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb

Publications and helpful links

Helpful Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting

Study record dates

Study Major Dates

• Study Start (Actual): April 28, 2022
• Primary Completion (Actual): July 14, 2025
• Study Completion (Actual): July 14, 2025

Study Registration Dates

• First Submitted: March 14, 2022
• First Submitted That Met QC Criteria: April 13, 2022
• First Posted (Actual): April 14, 2022

Study Record Updates

• Last Update Posted (Actual): August 26, 2026
• Last Update Submitted That Met QC Criteria: August 5, 2026
• Last Verified: August 1, 2026

More Information

Terms related to this study

• Keywords: Nivolumab; Regorafenib; Relatlimab; Lonsurf; Micro-satellite Stable (MSS) Metastatic Colorectal Cancer (mCRC); BMS-986213; Stivarga
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms by Site; Neoplasms; Genetic Diseases, Inborn; Intestinal Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Neurodegenerative Diseases; Colonic Diseases; Heredodegenerative Disorders, Nervous System; Spinal Cord Diseases; Cerebellar Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Colorectal Neoplasms; Spinocerebellar Degenerations; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Anti-Infective Agents; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Antimetabolites; Antiviral Agents; trifluridine tipiracil drug combination; regorafenib
• Other Study ID Numbers: CA224-123; 2021-004285-35 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No