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

• ClinicalTrials.gov Identifier: NCT05328908
• Recruitment Status: Recruiting
• First Posted: April 14, 2022
• Last Update Posted: May 16, 2023
• Sponsor: Bristol-Myers Squibb
• Information provided by (Responsible Party): Bristol-Myers Squibb

Tracking Information

• First Submitted Date: March 14, 2022
• First Posted Date: April 14, 2022
• Last Update Posted Date: May 16, 2023
• Actual Study Start Date: April 28, 2022
• Estimated Primary Completion Date: January 29, 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 13, 2022)

• Overall survival (OS) in randomized participants with programmed death-ligand 1 (PD-L1) combined positive score (CPS) ≥ 1 [ Time Frame: Up to 5 years after last participant randomized ]
• OS in all randomized participants [ Time Frame: Up to 5 years after last participant randomized ]

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: August 16, 2022)

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

Original Secondary Outcome Measures (submitted: April 13, 2022)

• 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 [ Time Frame: Up to 5 years after last participant randomized ]
• ORR by BICR per RECIST v1.1 in all randomized participants [ Time Frame: 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 [ Time Frame: Up to 5 years after last participant randomized ]
• PFS by BICR per RECIST v1.1 in all randomized participants [ Time Frame: 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 [ Time Frame: Up to 5 years after last participant randomized ]
• DoR by BICR per RECIST v1.1 in all responders [ Time Frame: Up to 5 years after last participant randomized ]
• Number of participants with adverse events (AEs) [ Time Frame: Up to 135 days after participant's last dose ]
• Number of participants with serious adverse events (SAEs) [ Time Frame: Up to 135 days after participant's last dose ]
• Number of participants with immune-mediated adverse events (IMAEs) [ Time Frame: Up to 135 days after participant's last dose ]
• Number of participants with AEs leading to discontinuation [ Time Frame: Up to 135 day's after participant's last dose ]
• Number of participants with clinical laboratory abnormalities [ Time Frame: Up to 135 days after participant's last dose ]
• DeFS-QoL: The time from randomization to death or at least a 15-points worsening from baseline in the EORTC QLQ-C30 GHS/QoL scale, with no subsequent improvement above the 15-point worsening from baseline score [ Time Frame: Up to 5 years after last participant randomized ]
  DeFS-QoL = Deterioration Free Survival-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.
• DeFS-PF: The time from randomization to death or at least a 10-points worsening from baseline in the EORTC QLQ-C30 physical function scale, with no subsequent improvement above the 10-point worsening from baseline score [ Time Frame: Up to 5 years after last participant randomized ]
  DeFS-PF = Deterioration Free Survival-Physical Function. 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.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Colorectal Neoplasms

Intervention

• Drug: Nivolumab-relatlimab FDC
  Specified dose on specified days
  Other Name: BMS-986213
• Drug: Regorafenib
  Specified dose on specified days
  Other Name: Stivarga
• Drug: TAS-102
  Specified dose on specified days
  Other Names:

  • Trifluridine/Tipiracil
  • Lonsurf

Study Arms

• Experimental: Arm A: Nivolumab + Relatlimab Fixed-dose Combination (FDC)
  Intervention: Drug: Nivolumab-relatlimab FDC
• Active Comparator: Arm B: Investigator's Choice
  Treatment with Regorafenib or TAS-102
  Interventions:

  • Drug: Regorafenib
  • Drug: TAS-102

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: April 13, 2022): 700
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: May 31, 2028
• Estimated Primary Completion Date: January 29, 2025 (Final data collection date for primary outcome measure)

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:

  1. 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), which must include a fluoropyrimidine, oxaliplatin, irinotecan, an anti-VEGF therapy, and anti-EGFR therapy (if KRAS wild-type), if available in the respective country, or;
  2. 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: BMS Study Connect Contact Center www.BMSStudyConnect.com; 855-907-3286; Clinical.Trials@bms.com

Contact: First line of the email MUST contain NCT # and Site #.

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

Administrative Information

• NCT Number: NCT05328908
• Other Study ID Numbers: CA224-123; 2021-004285-35 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Bristol-Myers Squibb
• Original Responsible Party: Same as current
• Current Study Sponsor: Bristol-Myers Squibb
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Bristol-Myers Squibb; Bristol-Myers Squibb

• PRS Account: Bristol-Myers Squibb
• Verification Date: May 2023