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

Colorectal Neoplasms Clinical Trial

— RELATIVITY-123  

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05328908
• Other study ID #: CA224-123
• Secondary ID: 2021-004285-35
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: April 28, 2022
• Est. completion date: May 31, 2028

Study information

• Verified date: February 2024
• Source: Bristol-Myers Squibb
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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) participants who failed at least 1 but no more than 4 prior lines of therapy for metastatic disease.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 700
• Est. completion date: May 31, 2028
• Est. primary completion date: January 29, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Colorectal Neoplasms

Intervention

Drug:
• Nivolumab-relatlimab FDC
Specified dose on specified days
• Regorafenib
Specified dose on specified days
• TAS-102
Specified dose on specified days

Locations

Country	Name	City	State
Argentina	Local Institution - 0022	Ciudad Autónoma Buenos Aires	Buenos Aires
Argentina	Local Institution - 0024	Ciudad Autónoma Buenos Aires
Argentina	Local Institution - 0026	Ciudad Autónoma Buenos Aires	B
Argentina	Local Institution - 0023	Rio Grande
Australia	Local Institution - 0010	Clayton	Victoria
Australia	Local Institution - 0001	Greenslopes	Queensland
Australia	Local Institution - 0021	Melbourne	Victoria
Australia	Local Institution - 0027	Murdoch	Western Australia
Australia	Local Institution - 0098	Wagga Wagga	New South Wales
Australia	Local Institution - 0114	Westmead	New South Wales
Austria	Local Institution - 0030	Graz
Austria	Local Institution - 0078	Klagenfurt Am Woerthersee
Austria	Local Institution - 0131	Salzburg
Belgium	Local Institution - 0070	Edegem
Belgium	Local Institution - 0068	Gent	VOV
Belgium	Local Institution - 0120	Leuven
Belgium	Local Institution - 0062	Woluwé-Saint-Lambert	BRU
Canada	Local Institution - 0003	Edmonton	Alberta
Canada	Local Institution - 0019	Montreal	Quebec
Canada	Local Institution - 0104	Montreal	Quebec
Canada	Local Institution - 0014	Ottawa	Ontario
Canada	Local Institution - 0004	Sherbrooke	Quebec
Canada	Local Institution - 0007	Toronto	Ontario
Chile	Local Institution - 0015	Santiago	RM
Chile	Local Institution - 0033	Santiago	RM
China	Local Institution - 0122	Beijing
China	Local Institution - 0138	Changsha	Hunan
China	Local Institution - 0158	Changsha	Hunan
China	Local Institution - 0144	Chengdu	Sichuan
China	Local Institution - 0134	Chongqing	CQ
China	Local Institution - 0151	Guangzhou	Guangdong
China	Local Institution - 0139	Hangzhou
China	Local Institution - 0160	Hangzhou Shi	Zhejiang
China	Local Institution - 0146	Huaian	Jiangsu
China	Local Institution - 0142	Jinan	Shandong
China	Local Institution - 0143	Nanjing	Jiangsu
China	Local Institution - 0153	Shanghai
China	Local Institution - 0149	Shenyang
China	Local Institution - 0141	Taiyuan	Shanxi
China	Local Institution - 0150	Tianjin	Tianjin
China	Local Institution - 0126	Wuhan	HB
China	Local Institution - 0164	Wuhan Shi	Hubei
China	Local Institution - 0152	Xi'an	SHA
Czechia	Local Institution - 0099	Horovice
Czechia	Local Institution - 0016	Hradec Králové
Czechia	Local Institution - 0100	Olomouc
Czechia	Local Institution - 0123	Ostrava
Czechia	Local Institution - 0064	Praha 5
France	Local Institution - 0066	Bordeaux
France	Local Institution - 0017	Caen
France	Local Institution - 0090	Dijon
France	Local Institution - 0020	Levallois-Perret
France	Local Institution - 0036	Lyon
France	Local Institution - 0089	Paris
France	Local Institution - 0039	Suresnes
Germany	Local Institution - 0055	Berlin	BE
Germany	Local Institution - 0101	Essen	Northwest
Germany	Local Institution - 0041	Frankfurt A. Main	HE
Germany	Local Institution - 0040	Hamburg
Germany	Local Institution - 0054	Mannheim	BW
Germany	Local Institution - 0034	Munchen
Germany	Local Institution - 0056	Reutlingen	BW
Germany	Local Institution - 0053	Wuerzburg	BY
Italy	Local Institution - 0060	Catania
Italy	Local Institution - 0091	Genova
Italy	Local Institution - 0045	Milan
Italy	Local Institution - 0046	Milano	MI
Italy	Local Institution - 0061	Napoli
Italy	Local Institution - 0115	Napoli
Italy	Local Institution - 0148	Padova	PD
Italy	Local Institution - 0059	Reggio Emilia	RE
Japan	Local Institution - 0107	Chiba-Shi
Japan	Local Institution - 0103	Chuo-Ku
Japan	Local Institution - 0105	Hidaka-shi
Japan	Local Institution - 0154	Kasama-Shi
Japan	Local Institution - 0084	Kashiwa-Shi
Japan	Local Institution - 0086	Kawasaki-Shi
Japan	Local Institution - 0119	Kitaadachi-gun
Japan	Local Institution - 0108	Koto-Ku
Japan	Local Institution - 0118	Matsuyama City
Japan	Local Institution - 0110	Osaka-shi	Osaka
Japan	Local Institution - 0088	Sapporo-shi
Japan	Local Institution - 0083	Suita-Shi
Japan	Local Institution - 0085	Sunto-gun
Japan	Local Institution - 0124	Yokohama-Shi
Korea, Republic of	Local Institution - 0073	Goyang-si, Gyeonggi-do
Korea, Republic of	Local Institution - 0129	Seongnamsi Bundanggu
Korea, Republic of	Local Institution - 0072	Seoul	Seoul-teukbyeolsi
Korea, Republic of	Local Institution - 0074	Seoul
Korea, Republic of	Local Institution - 0075	Seoul
Korea, Republic of	Local Institution - 0092	Seoul
Netherlands	Local Institution - 0050	Amsterdam
Poland	Local Institution - 0018	Kraków
Poland	Local Institution - 0051	Warsaw	MZ
Poland	Local Institution - 0037	Warszawa	Pl-mz
Poland	Local Institution - 0052	Warszawa
Puerto Rico	Local Institution - 0106	San Juan
Singapore	Local Institution - 0087	Singapore
Singapore	Local Institution - 0109	Singapore
Spain	Local Institution - 0029	Badalona	B
Spain	Local Institution - 0080	Barcelona
Spain	Local Institution - 0093	Barcelona	B
Spain	Local Institution - 0112	La Coruña
Spain	Local Institution - 0102	Madrid	M
Spain	Local Institution - 0113	Madrid
Spain	Local Institution - 0035	Sevilla
Spain	Local Institution - 0116	Zaragoza	Z
Sweden	Local Institution - 0067	Goteborg
Sweden	Local Institution - 0094	Malmö
Sweden	Local Institution - 0038	Stockholm	AB
Sweden	Local Institution - 0135	Stockholm	AB
Sweden	Local Institution - 0058	Uppsala	C
Switzerland	Local Institution - 0057	Aarau	AG
Switzerland	Local Institution - 0069	Bern
Taiwan	Local Institution - 0128	Changhua	CHA
Taiwan	Local Institution - 0111	Kaohsiung	KHH
Taiwan	Local Institution - 0076	Tainan	TNN
Taiwan	Local Institution - 0077	Tainan
Taiwan	Local Institution - 0121	Zhongzheng	TPE
United States	Local Institution - 0042	Ann Arbor	Michigan
United States	Local Institution - 0031	Atlanta	Georgia
United States	Local Institution - 0071	Boise	Idaho
United States	Massachusetts General Hospital,	Boston	Massachusetts
United States	Local Institution - 0008	Charleston	South Carolina
United States	Local Institution - 0082	Cincinnati	Ohio
United States	Local Institution - 0095	Columbus	Ohio
United States	Local Institution - 0009	Durham	North Carolina
United States	Local Institution - 0043	East Brunswick	New Jersey
United States	Local Institution - 0081	Fort Wayne	Indiana
United States	Local Institution - 0097	Fort Worth	Texas
United States	Local Institution - 0012	Los Angeles	California
United States	Local Institution - 0005	Madison	Wisconsin
United States	Local Institution - 0025	Miami	Florida
United States	Local Institution - 0127	Nashville	Tennessee
United States	Local Institution - 0117	Norwich	Connecticut
United States	Local Institution - 0147	Philadelphia	Pennsylvania
United States	Local Institution - 0132	Richmond	Virginia
United States	Local Institution - 0096	Sioux Falls	South Dakota
United States	Local Institution - 0044	Springdale	Arkansas

Sponsors (1)

Lead Sponsor	Collaborator
Bristol-Myers Squibb

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Austria,  Belgium,  Canada,  Chile,  China,  Czechia,  France,  Germany,  Italy,  Japan,  Korea, Republic of,  Netherlands,  Poland,  Puerto Rico,  Singapore,  Spain,  Sweden,  Switzerland,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	OS in all randomized participants		Up to 5 years after last participant randomized
Secondary	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
Secondary	ORR by BICR per RECIST v1.1 in all randomized participants		Up to 5 years after last participant randomized
Secondary	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
Secondary	PFS by BICR per RECIST v1.1 in all randomized participants		Up to 5 years after last participant randomized
Secondary	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
Secondary	DoR by BICR per RECIST v1.1 in all responders		Up to 5 years after last participant randomized
Secondary	Number of participants with adverse events (AEs)		Up to 135 days after participant's last dose
Secondary	Number of participants with serious adverse events (SAEs)		Up to 135 days after participant's last dose
Secondary	Number of participants with immune-mediated adverse events (IMAEs)		Up to 135 days after participant's last dose
Secondary	Number of participants with AEs leading to discontinuation		Up to 135 day's after participant's last dose
Secondary	Number of participants with clinical laboratory abnormalities		Up to 135 days after participant's last dose
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	PFS by investigator per RECIST v1.1 in randomized participants with PD-L1 CPS = 1		Up to 5 years after last participant randomized
Secondary	PFS by investigator per RECIST v1.1 in all randomized participants		Up to 5 years after last participant randomized
Secondary	ORR by investigator per RECIST v1.1 in randomized participants with PD-L1 CPS = 1		Up to 5 years after last participant randomized
Secondary	ORR by investigator per RECIST v1.1 in all randomized participants		Up to 5 years after last participant randomized
Secondary	DoR by investigator per RECIST v1.1 in responders with PD-L1 CPS = 1		Up to 5 years after last participant randomized
Secondary	DoR by investigator per RECIST v1.1 in all randomized participants		Up to 5 years after last participant randomized

External Links

•   BMS Clinical Trial Information
•   BMS Clinical Trial Patient Recruiting