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: Active, not recruiting
• Conditions: Colorectal Neoplasms
• Intervention / Treatment: Drug: Regorafenib; Drug: Nivolumab-relatlimab FDC; Drug: TAS-102

• Study Type: Interventional
• Enrollment (Estimated): 700
• 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 Am Woerthersee, 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
    • Gent, 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
  • Hubei
    • Wuhan Shi, Hubei, China, 430079
      • Local Institution - 0164
  • Hunan
    • Changsha, Hunan, China, 410013
      • Local Institution - 0138
    • Changsha, Hunan, China, 410013
      • Local Institution - 0158
  • Jiangsu
    • Huaian, Jiangsu, China, 223300
      • Local Institution - 0146
    • Nanjing, Jiangsu, China, 210008
      • Local Institution - 0143
  • SHA
    • Xi'an, SHA, China, 710038
      • Local Institution - 0152
  • Shandong
    • Jinan, Shandong, China, 250117
      • Local Institution - 0142
  • Shanxi
    • Taiyuan, Shanxi, China, 030013
      • Local Institution - 0141
  • Sichuan
    • Chengdu, Sichuan, China, 610041
      • Local Institution - 0144
  • Tianjin
    • Tianjin, Tianjin, China, 300121
      • Local Institution - 0150
  • Zhejiang
    • Hangzhou Shi, Zhejiang, China, 310022
      • Local Institution - 0160
• Czechia
  • Horovice, 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
  • Praha 5, Czechia, 150 06
    • Local Institution - 0064
• France
  • Bordeaux, France, 33000
    • Local Institution - 0066
  • Caen, France, 14000
    • Local Institution - 0017
  • 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
• Germany
  • Hamburg, Germany, 20249
    • Local Institution - 0040
  • Munchen, Germany, 81377
    • Local Institution - 0034
  • BE
    • Berlin, BE, Germany, 13353
      • Local Institution - 0055
  • BW
    • Mannheim, BW, Germany, 68167
      • Local Institution - 0054
    • Reutlingen, BW, Germany, 72764
      • Local Institution - 0056
  • BY
    • Wuerzburg, BY, Germany, 97080
      • Local Institution - 0053
  • HE
    • Frankfurt A. Main, HE, Germany, 60488
      • Local Institution - 0041
  • Northwest
    • Essen, Northwest, Germany, 45147
      • Local Institution - 0101
• Italy
  • Catania, Italy, 95122
    • Local Institution - 0060
  • Genova, Italy, 16132
    • Local Institution - 0091
  • Milan, Italy, 20133
    • Local Institution - 0045
  • Napoli, Italy, 80131
    • Local Institution - 0115
  • Napoli, Italy, 80138
    • Local Institution - 0061
  • MI
    • Milano, 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-Shi, Japan, 260-8717
    • Local Institution - 0107
  • Chuo-Ku, 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
  • Koto-Ku, Japan, 135-8550
    • Local Institution - 0108
  • Matsuyama City, Japan, 791-0280
    • Local Institution - 0118
  • Sapporo-shi, Japan, 060-8648
    • Local Institution - 0088
  • Suita-Shi, Japan, 565-0871
    • Local Institution - 0083
  • Sunto-gun, Japan, 411-8777
    • Local Institution - 0085
  • Yokohama-Shi, Japan, 241-8515
    • Local Institution - 0124
  • Osaka
    • Osaka-shi, Osaka, Japan, 5418567
      • Local Institution - 0110
• Korea, Republic of
  • Goyang-si, Gyeonggi-do, Korea, Republic of, 10408
    • Local Institution - 0073
  • Seongnamsi Bundanggu, Korea, Republic of, 13620
    • Local Institution - 0129
  • Seoul, Korea, Republic of, 05505
    • Local Institution - 0092
  • Seoul, Korea, Republic of, 06351
    • Local Institution - 0075
  • Seoul, Korea, Republic of, 110-744
    • Local Institution - 0074
  • Seoul-teukbyeolsi
    • Seoul, Seoul-teukbyeolsi, Korea, Republic of, 03722
      • Local Institution - 0072
• Netherlands
  • Amsterdam, Netherlands, 1066 CX
    • Local Institution - 0050
• Poland
  • Kraków, Poland, 30-727
    • Local Institution - 0018
  • Warszawa, Poland, 02-781
    • Local Institution - 0052
  • MZ
    • Warsaw, MZ, Poland, 02-507
      • Local Institution - 0051
  • Pl-mz
    • Warszawa, Pl-mz, Poland, 05-400
      • Local Institution - 0037
• Puerto Rico
  • San Juan, Puerto Rico, 00927
    • Local Institution - 0106
• Singapore
  • Singapore, Singapore, 169610
    • Local Institution - 0109
  • Singapore, Singapore, 329563
    • Local Institution - 0087
• Spain
  • Barcelona, Spain, 08035
    • Local Institution - 0080
  • La Coruña, Spain, 15006
    • Local Institution - 0112
  • Madrid, Spain, 28046
    • Local Institution - 0113
  • Sevilla, 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
  • Z
    • Zaragoza, Z, Spain, 50009
      • Local Institution - 0116
• Sweden
  • Goteborg, 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
  • AG
    • Aarau, AG, Switzerland, 5000
      • Local Institution - 0057
• Taiwan
  • Tainan, Taiwan, 70403
    • Local Institution - 0077
  • CHA
    • Changhua, CHA, Taiwan, 500
      • Local Institution - 0128
  • KHH
    • Kaohsiung, 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	Time Frame
Overall survival (OS) in randomized participants with programmed death-ligand 1 (PD-L1) combined positive score (CPS) ≥ 1	Up to 5 years after last participant randomized
OS in all randomized participants	Up to 5 years after last participant randomized

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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		Up to 5 years after last participant randomized
ORR by BICR per RECIST v1.1 in all randomized participants		Up to 5 years after last participant randomized
Progression-free survival (PFS) by BICR per RECIST v1.1 in randomized participants with PD-L1 CPS ≥ 1		Up to 5 years after last participant randomized
PFS by BICR per RECIST v1.1 in all randomized participants		Up to 5 years after last participant randomized
Duration of response (DoR) by BICR per RECIST v1.1 in responders with PD-L1 CPS ≥ 1		Up to 5 years after last participant randomized
DoR by BICR per RECIST v1.1 in all responders		Up to 5 years after last participant randomized
Number of participants with adverse events (AEs)		Up to 135 days after participant's last dose
Number of participants with serious adverse events (SAEs)		Up to 135 days after participant's last dose
Number of participants with immune-mediated adverse events (IMAEs)		Up to 135 days after participant's last dose
Number of participants with AEs leading to discontinuation		Up to 135 day's after participant's last dose
Number of participants with clinical laboratory abnormalities		Up to 135 days after participant's last dose
Time Until Definitive Deterioration-Physical Function (TUDD-PF): The time from randomization until definitive deterioration in the EORTC QLQ-C30 physical function scale score in randomized participants with PD-L1 CPS ≥ 1	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.	Up to follow up visit 2 (approximately 135 days after last dose)
TUDD-PF: The time from randomization until definitive deterioration in the EORTC QLQ-C30 physical function scale score in all randomized participants		Up to follow up visit 2 (approximately 135 days after last dose)
TUDD-QoL: The time from randomization until definitive deterioration in the EORTC QLQ-C30 global health status/QoL scale score in randomized participants with PD-L1 CPS ≥ 1	QoL = 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.	Up to follow up visit 2 (approximately 135 days after last dose)
TUDD-QoL: The time from randomization until definitive deterioration in the EORTC QLQ-C30 global health status/QoL scale score in all randomized participants		Up to follow up visit 2 (approximately 135 days after last dose)
PFS by investigator per RECIST v1.1 in randomized participants with PD-L1 CPS ≥ 1		Up to 5 years after last participant randomized
PFS by investigator per RECIST v1.1 in all randomized participants		Up to 5 years after last participant randomized
ORR by investigator per RECIST v1.1 in randomized participants with PD-L1 CPS ≥ 1		Up to 5 years after last participant randomized
ORR by investigator per RECIST v1.1 in all randomized participants		Up to 5 years after last participant randomized
DoR by investigator per RECIST v1.1 in responders with PD-L1 CPS ≥ 1		Up to 5 years after last participant randomized
DoR by investigator per RECIST v1.1 in all randomized participants		Up to 5 years after last participant randomized

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 (Estimated): January 29, 2025
• Study Completion (Estimated): May 31, 2028

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 (Estimated): March 1, 2024
• Last Update Submitted That Met QC Criteria: February 29, 2024
• Last Verified: February 1, 2024

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: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Antimetabolites; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Nivolumab; Trifluridine; Relatlimab
• 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