Clinical trial NCT05328908: A Study of Nivolumab-relatlimab Fixed-dose Combination Versus Regorafenib or TAS-102 in Participants With Later-lines of Metastatic Colorectal Cancer
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Colorectal Neoplasms
Keywords: Micro-satellite Stable (MSS) Metastatic Colorectal Cancer (mCRC)
Relatlimab
Nivolumab
BMS-986213
Regorafenib
Stivarga
Lonsurf
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2022-04-14
Enrollment: 700
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Overall survival (OS) in randomized participants with programmed death-ligand 1 (PD-L1) combined positive score (CPS) ≥ 1
timeFrame: Up to 5 years after last participant randomized
measure: OS in all randomized participants
timeFrame: Up to 5 years after last participant randomized
Secondary outcomes:
measure: 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
timeFrame: Up to 5 years after last participant randomized
measure: ORR by BICR per RECIST v1.1 in all randomized participants
timeFrame: Up to 5 years after last participant randomized
measure: Progression-free survival (PFS) by BICR per RECIST v1.1 in randomized participants with PD-L1 CPS ≥ 1
timeFrame: Up to 5 years after last participant randomized
measure: PFS by BICR per RECIST v1.1 in all randomized participants
timeFrame: Up to 5 years after last participant randomized
measure: Duration of response (DoR) by BICR per RECIST v1.1 in responders with PD-L1 CPS ≥ 1
timeFrame: Up to 5 years after last participant randomized
measure: DoR by BICR per RECIST v1.1 in all responders
timeFrame: Up to 5 years after last participant randomized
measure: Number of participants with adverse events (AEs)
timeFrame: Up to 135 days after participant's last dose
measure: Number of participants with serious adverse events (SAEs)
timeFrame: Up to 135 days after participant's last dose
measure: Number of participants with immune-mediated adverse events (IMAEs)
timeFrame: Up to 135 days after participant's last dose
measure: Number of participants with AEs leading to discontinuation
timeFrame: Up to 135 day's after participant's last dose
measure: Number of participants with clinical laboratory abnormalities
timeFrame: Up to 135 days after participant's last dose
measure: 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
timeFrame: Up to follow up visit 2 (approximately 135 days after last dose)
measure: TUDD-PF: The time from randomization until definitive deterioration in the EORTC QLQ-C30 physical function scale score in all randomized participants
timeFrame: Up to follow up visit 2 (approximately 135 days after last dose)
measure: 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
timeFrame: Up to follow up visit 2 (approximately 135 days after last dose)
measure: TUDD-QoL: The time from randomization until definitive deterioration in the EORTC QLQ-C30 global health status/QoL scale score in all randomized participants
timeFrame: Up to follow up visit 2 (approximately 135 days after last dose)
measure: PFS by investigator per RECIST v1.1 in randomized participants with PD-L1 CPS ≥ 1
timeFrame: Up to 5 years after last participant randomized
measure: PFS by investigator per RECIST v1.1 in all randomized participants
timeFrame: Up to 5 years after last participant randomized
measure: ORR by investigator per RECIST v1.1 in randomized participants with PD-L1 CPS ≥ 1
timeFrame: Up to 5 years after last participant randomized
measure: ORR by investigator per RECIST v1.1 in all randomized participants
timeFrame: Up to 5 years after last participant randomized
measure: DoR by investigator per RECIST v1.1 in responders with PD-L1 CPS ≥ 1
timeFrame: Up to 5 years after last participant randomized
measure: DoR by investigator per RECIST v1.1 in all randomized participants
timeFrame: Up to 5 years after last participant randomized
Other outcomes:
Locations:
city: Springdale
country: United States
facility: Local Institution - 0044
state: Arkansas
city: Los Angeles
country: United States
facility: Local Institution - 0012
state: California
city: Norwich
country: United States
facility: Local Institution - 0117
state: Connecticut
city: Miami
country: United States
facility: Local Institution - 0025
state: Florida
city: Atlanta
country: United States
facility: Local Institution - 0031
state: Georgia
city: Boise
country: United States
facility: Local Institution - 0071
state: Idaho
city: Fort Wayne
country: United States
facility: Local Institution - 0081
state: Indiana
city: Boston
country: United States
facility: Massachusetts General Hospital,
state: Massachusetts
city: Ann Arbor
country: United States
facility: Local Institution - 0042
state: Michigan
city: East Brunswick
country: United States
facility: Local Institution - 0043
state: New Jersey
city: Durham
country: United States
facility: Local Institution - 0009
state: North Carolina
city: Cincinnati
country: United States
facility: Local Institution - 0082
state: Ohio
city: Columbus
country: United States
facility: Local Institution - 0095
state: Ohio
city: Philadelphia
country: United States
facility: Local Institution - 0147
state: Pennsylvania
city: Charleston
country: United States
facility: Local Institution - 0008
state: South Carolina
city: Sioux Falls
country: United States
facility: Local Institution - 0096
state: South Dakota
city: Nashville
country: United States
facility: Local Institution - 0127
state: Tennessee
city: Fort Worth
country: United States
facility: Local Institution - 0097
state: Texas
city: Richmond
country: United States
facility: Local Institution - 0132
state: Virginia
city: Madison
country: United States
facility: Local Institution - 0005
state: Wisconsin
city: Ciudad Autónoma Buenos Aires
country: Argentina
facility: Local Institution - 0022
state: Buenos Aires
city: Ciudad Autónoma Buenos Aires
country: Argentina
facility: Local Institution - 0026
state: B
city: Ciudad Autónoma Buenos Aires
country: Argentina
facility: Local Institution - 0024
city: Rio Grande
country: Argentina
facility: Local Institution - 0023
city: Wagga Wagga
country: Australia
facility: Local Institution - 0098
state: New South Wales
city: Westmead
country: Australia
facility: Local Institution - 0114
state: New South Wales
city: Greenslopes
country: Australia
facility: Local Institution - 0001
state: Queensland
city: Clayton
country: Australia
facility: Local Institution - 0010
state: Victoria
city: Melbourne
country: Australia
facility: Local Institution - 0021
state: Victoria
city: Murdoch
country: Australia
facility: Local Institution - 0027
state: Western Australia
city: Graz
country: Austria
facility: Local Institution - 0030
city: Klagenfurt Am Woerthersee
country: Austria
facility: Local Institution - 0078
city: Salzburg
country: Austria
facility: Local Institution - 0131
city: Woluwé-Saint-Lambert
country: Belgium
facility: Local Institution - 0062
state: BRU
city: Gent
country: Belgium
facility: Local Institution - 0068
state: VOV
city: Edegem
country: Belgium
facility: Local Institution - 0070
city: Leuven
country: Belgium
facility: Local Institution - 0120
city: Edmonton
country: Canada
facility: Local Institution - 0003
state: Alberta
city: Ottawa
country: Canada
facility: Local Institution - 0014
state: Ontario
city: Toronto
country: Canada
facility: Local Institution - 0007
state: Ontario
city: Montreal
country: Canada
facility: Local Institution - 0019
state: Quebec
city: Montreal
country: Canada
facility: Local Institution - 0104
state: Quebec
city: Sherbrooke
country: Canada
facility: Local Institution - 0004
state: Quebec
city: Santiago
country: Chile
facility: Local Institution - 0015
state: RM
city: Santiago
country: Chile
facility: Local Institution - 0033
state: RM
city: Chongqing
country: China
facility: Local Institution - 0134
state: CQ
city: Guangzhou
country: China
facility: Local Institution - 0151
state: Guangdong
city: Wuhan
country: China
facility: Local Institution - 0126
state: HB
city: Wuhan Shi
country: China
facility: Local Institution - 0164
state: Hubei
city: Changsha
country: China
facility: Local Institution - 0138
state: Hunan
city: Changsha
country: China
facility: Local Institution - 0158
state: Hunan
city: Huaian
country: China
facility: Local Institution - 0146
state: Jiangsu
city: Nanjing
country: China
facility: Local Institution - 0143
state: Jiangsu
city: Jinan
country: China
facility: Local Institution - 0142
state: Shandong
city: Taiyuan
country: China
facility: Local Institution - 0141
state: Shanxi
city: Xi'an
country: China
facility: Local Institution - 0152
state: SHA
city: Chengdu
country: China
facility: Local Institution - 0144
state: Sichuan
city: Tianjin
country: China
facility: Local Institution - 0150
state: Tianjin
city: Hangzhou Shi
country: China
facility: Local Institution - 0160
state: Zhejiang
city: Beijing
country: China
facility: Local Institution - 0122
city: Hangzhou
country: China
facility: Local Institution - 0139
city: Shanghai
country: China
facility: Local Institution - 0153
city: Shenyang
country: China
facility: Local Institution - 0149
city: Horovice
country: Czechia
facility: Local Institution - 0099
city: Hradec Králové
country: Czechia
facility: Local Institution - 0016
city: Olomouc
country: Czechia
facility: Local Institution - 0100
city: Ostrava
country: Czechia
facility: Local Institution - 0123
city: Praha 5
country: Czechia
facility: Local Institution - 0064
city: Bordeaux
country: France
facility: Local Institution - 0066
city: Caen
country: France
facility: Local Institution - 0017
city: Dijon
country: France
facility: Local Institution - 0090
city: Levallois-Perret
country: France
facility: Local Institution - 0020
city: Lyon
country: France
facility: Local Institution - 0036
city: Paris
country: France
facility: Local Institution - 0089
city: Suresnes
country: France
facility: Local Institution - 0039
city: Berlin
country: Germany
facility: Local Institution - 0055
state: BE
city: Mannheim
country: Germany
facility: Local Institution - 0054
state: BW
city: Reutlingen
country: Germany
facility: Local Institution - 0056
state: BW
city: Wuerzburg
country: Germany
facility: Local Institution - 0053
state: BY
city: Frankfurt A. Main
country: Germany
facility: Local Institution - 0041
state: HE
city: Essen
country: Germany
facility: Local Institution - 0101
state: Northwest
city: Hamburg
country: Germany
facility: Local Institution - 0040
city: Munchen
country: Germany
facility: Local Institution - 0034
city: Milano
country: Italy
facility: Local Institution - 0046
state: MI
city: Padova
country: Italy
facility: Local Institution - 0148
state: PD
city: Reggio Emilia
country: Italy
facility: Local Institution - 0059
state: RE
city: Catania
country: Italy
facility: Local Institution - 0060
city: Genova
country: Italy
facility: Local Institution - 0091
city: Milan
country: Italy
facility: Local Institution - 0045
city: Napoli
country: Italy
facility: Local Institution - 0115
city: Napoli
country: Italy
facility: Local Institution - 0061
city: Osaka-shi
country: Japan
facility: Local Institution - 0110
state: Osaka
city: Chiba-Shi
country: Japan
facility: Local Institution - 0107
city: Chuo-Ku
country: Japan
facility: Local Institution - 0103
city: Hidaka-shi
country: Japan
facility: Local Institution - 0105
city: Kasama-Shi
country: Japan
facility: Local Institution - 0154
city: Kashiwa-Shi
country: Japan
facility: Local Institution - 0084
city: Kawasaki-Shi
country: Japan
facility: Local Institution - 0086
city: Kitaadachi-gun
country: Japan
facility: Local Institution - 0119
city: Koto-Ku
country: Japan
facility: Local Institution - 0108
city: Matsuyama City
country: Japan
facility: Local Institution - 0118
city: Sapporo-shi
country: Japan
facility: Local Institution - 0088
city: Suita-Shi
country: Japan
facility: Local Institution - 0083
city: Sunto-gun
country: Japan
facility: Local Institution - 0085
city: Yokohama-Shi
country: Japan
facility: Local Institution - 0124
city: Seoul
country: Korea, Republic of
facility: Local Institution - 0072
state: Seoul-teukbyeolsi
city: Goyang-si, Gyeonggi-do
country: Korea, Republic of
facility: Local Institution - 0073
city: Seongnamsi Bundanggu
country: Korea, Republic of
facility: Local Institution - 0129
city: Seoul
country: Korea, Republic of
facility: Local Institution - 0092
city: Seoul
country: Korea, Republic of
facility: Local Institution - 0075
city: Seoul
country: Korea, Republic of
facility: Local Institution - 0074
city: Amsterdam
country: Netherlands
facility: Local Institution - 0050
city: Warsaw
country: Poland
facility: Local Institution - 0051
state: MZ
city: Warszawa
country: Poland
facility: Local Institution - 0037
state: Pl-mz
city: Kraków
country: Poland
facility: Local Institution - 0018
city: Warszawa
country: Poland
facility: Local Institution - 0052
city: San Juan
country: Puerto Rico
facility: Local Institution - 0106
city: Singapore
country: Singapore
facility: Local Institution - 0109
city: Singapore
country: Singapore
facility: Local Institution - 0087
city: Badalona
country: Spain
facility: Local Institution - 0029
state: B
city: Barcelona
country: Spain
facility: Local Institution - 0093
state: B
city: Madrid
country: Spain
facility: Local Institution - 0102
state: M
city: Zaragoza
country: Spain
facility: Local Institution - 0116
state: Z
city: Barcelona
country: Spain
facility: Local Institution - 0080
city: La Coruña
country: Spain
facility: Local Institution - 0112
city: Madrid
country: Spain
facility: Local Institution - 0113
city: Sevilla
country: Spain
facility: Local Institution - 0035
city: Stockholm
country: Sweden
facility: Local Institution - 0038
state: AB
city: Stockholm
country: Sweden
facility: Local Institution - 0135
state: AB
city: Uppsala
country: Sweden
facility: Local Institution - 0058
state: C
city: Goteborg
country: Sweden
facility: Local Institution - 0067
city: Malmö
country: Sweden
facility: Local Institution - 0094
city: Aarau
country: Switzerland
facility: Local Institution - 0057
state: AG
city: Bern
country: Switzerland
facility: Local Institution - 0069
city: Changhua
country: Taiwan
facility: Local Institution - 0128
state: CHA
city: Kaohsiung
country: Taiwan
facility: Local Institution - 0111
state: KHH
city: Tainan
country: Taiwan
facility: Local Institution - 0076
state: TNN
city: Zhongzheng
country: Taiwan
facility: Local Institution - 0121
state: TPE
city: Tainan
country: Taiwan
facility: Local Institution - 0077
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References: