This study has been transitioned to CTIS with ID 2023-503797-21-00 check the CTIS register for the current data. The purpose of this study is to determine if the combination of relatlimab and nivolumab improves overall survival (OS) in all…
ID
Source
Brief title
Condition
- Other condition
Synonym
Health condition
Later-lines of Metastatic Colorectal Cancer
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary End Point:
- Overall Survival (OS) in randomized participants with PD-L1 CPS (combined
positive score;) >= 1
- OS in all randomized participants
Secondary outcome
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
Background summary
This trial provides the opportunity to evaluate relatlimab in combination with
nivolumab, fixed-dose combination (relatlimab-nivolumab FDC, also referred to
as BMS-986213) for the treatment of late-line microsatellite stable (MSS)
metastatic colorectal cancer (mCRC) participants
who failed at least 1 but no more than 4 prior lines of therapy for metastatic
disease. In MSS mCRC, which represents approximately 85% to 96% of the CRC
patient population, the tumor microenvironment is immunosuppressive, blunting
activation of anti-tumor immune responses. Treatment after standard first line
and second line therapies have limited clinical impact, with objective response
rate less than 2%, and median overall survival 6-8 months. Lymphocyte
activation gene-3 (LAG-3) is often expressed on chronically exhausted T-cells
and is frequently co-expressed with programmed death 1 (PD-1) on tolerized
tumor-infiltrating lymphocytes including immunosuppressive T-regulatory cell.
As such, combining a LAG-3 inhibitor and an
anti-programmed death (PD)-1/PD-L1 agent has the potential to bolster tumor
immune surveillance across tumor types, including MSS mCRC.
Study objective
This study has been transitioned to CTIS with ID 2023-503797-21-00 check the CTIS register for the current data.
The purpose of this study is to determine if the combination of relatlimab and
nivolumab improves overall survival (OS) in all randomized participants and
participants with PD-L1 CPS >= 1 with later-line metastatic colorectal cancer
compared to the current standard of care, regorafenib or TAS-102.
Study design
In this open-label (sponsor blinded), randomized, Phase 3 study, approximately
700 participants with later-line MSS mCRC, including approximately 280
participants with PD-L1 combined positive score (CPS) >= 1, will be randomized
in a 1:1 ratio to receive the following:
Arm A: Relatlimab-nivolumab FDC 480 mg/480 mg intravenous infusions every 4
weeks (Q4W)
Arm B: Standard of care (SOC)*Regorafenib 160 mg once daily, orally for 21 days
of a 28-day cycle or trifluridine + tipiracil (TAS-102) 35 mg/m2, twice daily,
orally for Days 1 to 5 and Days 8 to 12 of each 28-day cycle
Intervention
Intervention Groups and Duration:
Participants will be randomized to Arm A or Arm B. All investigational agents
will be administered in an unblinded manner. Access to randomized treatment
codes will be restricted from BMS personnel prior to primary database lock with
exceptions. Dose reductions are not
permitted for immunotherapy study treatments (Arm A).
Dose reductions are allowed in Arm B according to the product label or
institutional guidelines.
Arm A: Relatlimab-nivolumab FDC 480 mg/480 mg Q4W
Arm B: Regorafenib, 160 mg, orally, once daily for the first 21 days of each
28-day cycle or
TAS-102, 35 mg/m2, orally, twice daily on Day 1 to 5 and Day 8 to 12 of each
28-day cycle (maximum of 80 mg per dose)
Study burden and risks
See Study Protocol 3.3.1 Risk Assessment
Chaussée de La Hulpe 185
Bruxelles 1170
BE
Chaussée de La Hulpe 185
Bruxelles 1170
BE
Listed location countries
Age
Inclusion criteria
- Histologically confirmed previously treated CRC with adenocarcinoma histology
with metastatic or recurrent unresectable disease at study entry.
- Participants must have:
a)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 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.
- 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 (see next slide for details).
- KRAS mutation status must be documented based on available historical or
local testing results as part of medical history prior to study enrollment.
- 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.
Exclusion criteria
- 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.
- 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)
- 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.
- 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.
- Participants with historically or locally confirmed tumor MSI-H/dMMR
status
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EU-CTR | CTIS2023-503797-21-00 |
| EudraCT | EUCTR2021-004285-35-NL |
| CCMO | NL80990.041.22 |