A Study of Relatlimab-nivolumab Fixed-dose Combination versus Regorafenib or TAS-102 in Participants with Later-lines of Metastatic Colorectal Cancer

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Bristol Myers Squibb International Corporation

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

10 Aug 2022 → 15 Jul 2025

Decision date (initial)

2024-02-05

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2023-503797-21-00

EudraCT number

2021-004285-35

WHO UTN

U1111-1268-4651

ClinicalTrials.gov

NCT05328908

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

To compare the efficacy of the relatlimab-nivolumab FDC to investigator's choice standard of care therapy (regorafenib or TAS-102) in participants with late-line metastatic colorectal cancer, including all randomized participants and randomized participants with PD-L1 CPS ≥ 1, respectively

Secondary objectives 3

1. To compare the antitumor activity based on ORR by BICR of the relatlimab-nivolumab FDC to investigator's choice standard of care therapy (regorafenib or TAS-102) in participants with late-line metastatic colorectal cancer, including all randomized participants and randomized participants with PD-L1 CPS ≥1
2. To compare the antitumor efficacy based on PFS by BICR of the relatlimab-nivolumab FDC to investigator's choice standard of care therapy (regorafenib or TAS-102) in participants with late-line metastatic colorectal cancer, including all randomized participants and randomized participants with PD-L1 CPS ≥ 1
3. To compare deterioration free survival (DeFS) of the relatlimab + nivolumab FDC to investigator's choice standard of care therapy (regorafenib or TAS- 102) in participants with late-line metastatic colorectal cancer, including all randomized participants and randomized participants with PD-L1 CPS ≥ 1

Conditions and MedDRA coding

Metastatic Colorectal Cancer

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

Yes

IPD plan description

BMS will provide access to individual anonymized participant data upon request from qualified researchers, and subject to certain criteria. Additional information regarding Bristol Myer Squibb's data sharing policy and process can be found at: https://www.bms.com/researchers-and-partners/clinical-trials-and-research/disclosure- commitment.html

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Histologically confirmed previously treated CRC with adenocarcinoma histology with metastatic or recurrent unresectable disease at study entry
2. Participants must have: a)progressed during or within approximately 3 months following the last administration of approved standard therapies in the metastatic setting (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 RAS wild-type), if approved in the respective country, or; b)been intolerant to prior systemic chemotherapy regimens if there is documented evidence of clinically significant intolerance despite adequate supportive measures.
3. Participants must have sufficient tumor tissue & evaluable PD-L1 expression to meet the study requirements. Participants with indeterminate PD-L1 results will be stratified with those participants assessed to be PD-L1 negative by CPS.
4. KRAS mutation status must be documented based on available historical or local testing results as part of medical history prior to study enrollment.
5. Participants 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
6. For all Inclusion Criteria please refer to the Protocol.

Exclusion criteria 6

1. Prior treatment with either an immunotherapy (anti-LAG-3, anti-PD-1, anti-PD-L1, or anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways) or with regorafenib or with TAS-102.
2. Untreated 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)
3. Participants with 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.
4. In the case of prior SARS-CoV-2 infection, acute symptoms must have completely resolved and based on investigator assessment in consultation with the clinical trial physician, there are no sequelae that would place the participant at a higher risk of receiving investigational treatment.
5. Participants with historically or locally confirmed tumor MSI-H/dMMR status
6. For all Exclusion Criteria, please refer to the Protocol.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Overall Survival (OS) in randomized participants with PD-L1 CPS (combined positive score;) ≥ 1
2. OS in all randomized participants

Secondary endpoints 7

1. ORR (objective response rate) by BICR (blinded independent central review) per RECIST v1.1 in randomized participants with PD-L1 CPS ≥ 1 and all randomized participants, respectively
2. PFS (progression-free survival) by BICR per RECIST v1.1 in randomized participants with PD-L1 CPS≥ 1 and all randomized participants, respectively
3. DoR (duration of response;) by BICR per RECIST v1.1 in responders with PD-L1 CPS ≥ 1 and all responders, respectively
4. Rate of AEs (adverse events), SAEs (serious adverse events), select AEs and IMAEs (immune-mediated adverse events), AEs leading to discontinuation and abnormalities in specific clinical laboratory assessments
5. QoLTUDD-physical function (TUDDPF), which is defined as time from randomization until definitive deterioration in the EORTC QLQ-C30 physical function scale score in randomized participants with PD-L1 CPS ≥ 1 and all randomized participants, respectively
6. TUDD-quality of life (TUDD-QoL), which is defined as time until definitive deterioration in the EORTC QLQ-C30 global health status/QoL scale score in randomized participants with PD-L1 CPS ≥ 1 and all randomized participants, Respectively
7. PFS, ORR, DoR by investigator per RECIST v1.1 in randomized participants with PD-L1 CPS = 1 and all randomized participants, respectively

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Comparator 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Bristol Myers Squibb International Corporation

Sponsor organisation

Bristol Myers Squibb International Corporation

Address

Terhulpsesteenweg 185

City

Watermaal-Bosvoorde

Postcode

1170

Country

Belgium

Scientific contact point

Organisation

Bristol Myers Squibb International Corporation

Contact name

GSM-CT

Public contact point

Organisation

Bristol Myers Squibb International Corporation

Contact name

GSM-CT

Third parties 15

Locations

10 EU/EEA countries · 49 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 83 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

8 submissions — initial application plus substantial / non-substantial modifications