Colorectal NeoplasmsPhase 3RELATIVITY-123NCT05328908
A Study of Nivolumab-relatlimab Fixed-dose Combination Versus Regorafenib or TAS-102 in Participants With Later-lines of Metastatic Colorectal Cancer
A Phase 3 study testing Nivolumab-relatlimab FDC, Regorafenib and TAS-102 in people with Colorectal Neoplasms, run by Bristol-Myers Squibb at 139 sites in 22 countries.
Trial 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)… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Colorectal Neoplasms
- What is being tested?
- Nivolumab-relatlimab FDC, Regorafenib and TAS-102
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 769 participants
- Where
- 139 sitesin 22 countries
- Study dates
- 28 Apr 2022to 14 Jul 2025
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histological confirmed previously treated colorectal cancer with adenocarcinoma histology with metastatic or recurrent unresectable disease at study entry.
- 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 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;.
- 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.
Who cannot join
- 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.
Trial locations and contacts
139 sites in 22 countries.
139 sites in 22 countries
United States20 sites
Local Institution - 0042
Ann Arbor, Michigan, 48109-1382
Local Institution - 0031
Atlanta, Georgia, 30342
Local Institution - 0071
Boise, Idaho, 83712-6267
Massachusetts General Hospital,
Boston, Massachusetts, 02214
Local Institution - 0008
Charleston, South Carolina, 29414
Local Institution - 0082
Cincinnati, Ohio, 45220
Local Institution - 0095
Columbus, Ohio, 43210-1240
Local Institution - 0009
Durham, North Carolina, 27710
Local Institution - 0043
East Brunswick, New Jersey, 08816-3340
Local Institution - 0081
Fort Wayne, Indiana, 46805
Local Institution - 0097
Fort Worth, Texas, 76104-4611
Local Institution - 0012
Los Angeles, California, 90089-0112
Local Institution - 0005
Madison, Wisconsin, 53705-2275
Local Institution - 0025
Miami, Florida, 33176
Local Institution - 0127
Nashville, Tennessee, 37203-2173
Local Institution - 0117
Norwich, Connecticut, 06360-2753
Local Institution - 0147
Philadelphia, Pennsylvania, 19111-2434
Local Institution - 0132
Richmond, Virginia, 23284
Local Institution - 0096
Sioux Falls, South Dakota, 57104
Local Institution - 0044
Springdale, Arkansas, 72762-5328
China18 sites
Local Institution - 0122
Beijing, 100142
Local Institution - 0138
Changsha, HN, 410013
Local Institution - 0158
Changsha, Hunan, 410013
Local Institution - 0144
Chengdu, Sichuan, 610041
Local Institution - 0134
Chongqing, CQ, 400030
Local Institution - 0151
Guangzhou, Guangdong, 510655
Local Institution - 0160
Hangzhou, ZJ, 310022
Local Institution - 0139
Hangzhou, 310003
Local Institution - 0146
Huaian, Jiangsu, 223300
Local Institution - 0142
Jinan, SD, 250117
Local Institution - 0143
Nanjing, JS, 210008
Local Institution - 0153
Shanghai, 200032
Local Institution - 0149
Shenyang, 110042
Local Institution - 0141
Taiyuan, SX, 030013
Local Institution - 0150
Tianjin, TJ, 300121
Local Institution - 0126
Wuhan, HB, 430071
Local Institution - 0164
Wuhan, Hubei, 430079
Local Institution - 0152
Xi'an, SHA, 710038
Japan14 sites
Local Institution - 0107
Chiba, 260-8717
Local Institution - 0103
Chūōku, 104-0045
Local Institution - 0105
Hidaka-shi, 350-1298
Local Institution - 0154
Kasama-Shi, 309-1793
Local Institution - 0084
Kashiwa-Shi, 277-8577
Local Institution - 0086
Kawasaki-Shi, 216-8511
Local Institution - 0119
Kitaadachi-gun, 362-0806
Local Institution - 0108
Kōtoku, 135-8550
Local Institution - 0118
Matsuyama, 791-0280
Local Institution - 0110
Osaka, Osaka, 5418567
Local Institution - 0088
Sapporo, 060-8648
Local Institution - 0083
Suita-Shi, 565-0871
Local Institution - 0085
Sunto-gun, 411-8777
Local Institution - 0124
Yokohama, 241-8515
Germany8 sites
Local Institution - 0055
Berlin, State of Berlin, 13353
Local Institution - 0101
Essen, North Rhine-Westphalia, 45147
Local Institution - 0041
Frankfurt A. Main, Hesse, 60488
Local Institution - 0040
Hamburg, 20249
Local Institution - 0054
Mannheim, Baden-Wurttemberg, 68167
Local Institution - 0034
München, 81377
Local Institution - 0056
Reutlingen, Baden-Wurttemberg, 72764
Local Institution - 0053
Würzburg, Bavaria, 97080
Italy8 sites
Local Institution - 0060
Catania, 95122
Local Institution - 0091
Genova, 16132
Local Institution - 0046
Milan, MI, 20162
Local Institution - 0045
Milan, 20133
Local Institution - 0115
Naples, 80131
Local Institution - 0061
Naples, 80138
Local Institution - 0148
Padova, PD, 35128
Local Institution - 0059
Reggio Emilia, RE, 42123
Spain8 sites
Local Institution - 0112
A Coruña, 15006
Local Institution - 0029
Badalona, B, 08916
Local Institution - 0093
Barcelona, B, 08036
Local Institution - 0080
Barcelona, 08035
Local Institution - 0113
Madrid, Madrid, 28046
Local Institution - 0102
Madrid, M, 28041
Local Institution - 0035
Seville, 41013
Local Institution - 0116
Zaragoza, Z, 50009
France7 sites
Local Institution - 0066
Bordeaux, 33000
Local Institution - 0017
Caen, Caen, 14000
Local Institution - 0090
Dijon, 21000
Local Institution - 0020
Levallois-Perret, 92300
Local Institution - 0036
Lyon, 69008
Local Institution - 0089
Paris, 75012
Local Institution - 0039
Suresnes, 92151
Australia6 sites
Local Institution - 0010
Clayton, Victoria, 3168
Local Institution - 0001
Greenslopes, Queensland, 4120
Local Institution - 0021
Melbourne, Victoria, 3084
Local Institution - 0027
Murdoch, Western Australia, 6150
Local Institution - 0098
Wagga Wagga, New South Wales, 2650
Local Institution - 0114
Westmead, New South Wales, 2145
Canada6 sites
Local Institution - 0003
Edmonton, Alberta, T6G 1Z2
Local Institution - 0019
Montreal, Quebec, H2X 3E4
Local Institution - 0104
Montreal, Quebec, H4A 3J1
Local Institution - 0014
Ottawa, Ontario, K1H 8L6
Local Institution - 0004
Sherbrooke, Quebec, J1H 5N4
Local Institution - 0007
Toronto, Ontario, M5G 2M9
South Korea6 sites
Local Institution - 0073
Goyang-si, Gyeonggi-do, 10408
Local Institution - 0129
Seongnamsi Bundanggu, 13620
Local Institution - 0072
Seoul, Seoul-teukbyeolsi, 03722
Local Institution - 0092
Seoul, 05505
Local Institution - 0075
Seoul, 06351
Local Institution - 0074
Seoul, 110-744
Czechia5 sites
Local Institution - 0099
Hořovice, 26801
Local Institution - 0016
Hradec Králové, 500 05
Local Institution - 0100
Olomouc, 775 20
Local Institution - 0123
Ostrava, 708 52
Local Institution - 0064
Prague, 150 06
Sweden5 sites
Local Institution - 0067
Gothenburg, 413 45
Local Institution - 0094
Malmö, 214 28
Local Institution - 0038
Stockholm, AB, 112 81
Local Institution - 0135
Stockholm, AB, 171 76
Local Institution - 0058
Uppsala, C, 751 85
Taiwan5 sites
Local Institution - 0128
Changhua, CHA, 500
Local Institution - 0111
Kaohsiung City, KHH, 83301
Local Institution - 0076
Tainan, TNN, 704
Local Institution - 0077
Tainan, 70403
Local Institution - 0121
Zhongzheng, TPE, 100
Argentina4 sites
Local Institution - 0022
Ciudad Autónoma Buenos Aires, Buenos Aires, 1425
Local Institution - 0026
Ciudad Autónoma Buenos Aires, B, C1181ACH
Local Institution - 0024
Ciudad Autónoma Buenos Aires, 1834
Local Institution - 0023
Rio Grande, 8500
Belgium4 sites
Local Institution - 0070
Edegem, 2650
Local Institution - 0068
Ghent, VOV, 9000
Local Institution - 0120
Leuven, 3000
Local Institution - 0062
Woluwé-Saint-Lambert, BRU, 1200
Poland4 sites
Local Institution - 0018
Krakow, 30-727
Local Institution - 0051
Warsaw, Masovian Voivodeship, 02-507
Local Institution - 0037
Warsaw, Pl-mz, 05-400
Local Institution - 0052
Warsaw, 02-781
Austria3 sites
Local Institution - 0030
Graz, 6800
Local Institution - 0078
Klagenfurt, 9020
Local Institution - 0131
Salzburg, 5020
Chile2 sites
Local Institution - 0015
Santiago, RM, 7560908
Local Institution - 0033
Santiago, RM, 8380456
Singapore2 sites
Local Institution - 0109
Singapore, 169610
Local Institution - 0087
Singapore, 329563
Switzerland2 sites
Local Institution - 0057
Aarau, Canton of Aargau, 5000
Local Institution - 0069
Bern, 3010
About this study
Official title: 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.
- Conditions
- Colorectal Neoplasms
- Being tested
- Nivolumab-relatlimab FDC, Regorafenib, TAS-102
- Keywords
- Micro-satellite Stable (MSS) Metastatic Colorectal Cancer (mCRC), Relatlimab, Nivolumab, BMS-986213, Regorafenib, Stivarga, Lonsurf
- Medical subject headings
- Colorectal Neoplasms, Spinocerebellar Degenerations
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Nivolumab-relatlimab FDCDrug
Also called BMS-986213
Specified dose on specified days
RegorafenibDrug
Also called Stivarga
Specified dose on specified days
TAS-102Drug
Also called Trifluridine/Tipiracil, Lonsurf
Specified dose on specified days
| Study group | Role | What they receive |
|---|---|---|
| Arm A: Nivolumab + Relatlimab Fixed-dose Combination (FDC) | Experimental | Not described Receives: Drug: Nivolumab-relatlimab FDC |
| Arm B: Investigator's Choice | Active comparator | Treatment with Regorafenib or TAS-102 Receives: Drug: Regorafenib; Drug: TAS-102 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Survival (OS)
OS is defined as the time from date of randomization to the date of death due to any cause.
Measured: From date of randomization to the date of death due to any cause (Up to approxaimtely 38 months)
Secondary outcomes (12)
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: From date of randomization to the date of first documented progression or death, whichever occurs first (Up to approximately 38 months)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Apr 2022
- Study start28 Apr 2022
- Primary completion14 Jul 2025
- Study completion14 Jul 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Colorectal NeoplasmsStudies of the same condition, open and under way.
- More trials run by Bristol-Myers SquibbThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 769 participants (actual)
Sponsor and investigators
- Lead sponsor
- Bristol-Myers Squibb
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Bristol-Myers Squibb, Study director, Bristol-Myers Squibb
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05328908
- Sponsor's protocol ID
- CA224-123
- Other IDs
- 2021-004285-35
- Acronym
- RELATIVITY-123
- Status last verified
- Aug 2026
- First submitted
- 14 Mar 2022
- Last updated
- 26 Aug 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Expanded access
- Available