What side effects are associated with this type of intervention?

Immune checkpoint inhibitors used in colorectal cancer treatment, such as nivolumab (anti-PD-1) and relatlimab (anti-LAG-3), commonly cause side effects like fatigue, rash, pruritus, diarrhea, and pneumonitis. Severe side effects can include colitis, hepatitis, endocrinopathies, and severe skin reactions, due to the enhanced immune response these drugs provoke.

What prior FDA approvals exist?

The FDA has approved several immunotherapy agents for the treatment of colorectal cancer, particularly for cases with specific genetic markers. Nivolumab, an anti-PD-1 antibody, has been approved for use in patients with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer that has progressed following treatment with fluoropyrimidine, oxaliplatin, and irinotecan. Pembrolizumab, another anti-PD-1 antibody, has also been approved for MSI-H or dMMR colorectal cancer. While relatlimab, an anti-LAG-3 antibody, is being studied in combination with nivolumab, it has not yet received FDA approval for colorectal cancer treatment.

What other types of research exist?

Promising alternatives to Relatlimab and Nivolumab for colorectal cancer patients include Avelumab (anti-PD-L1) and Pembrolizumab (anti-PD-1). Additionally, combination therapies involving these agents with other immune modulators or chemotherapy are being explored. For patients with dMMR/MSI tumors, these alternatives may offer significant benefits.

← Back to Search

Checkpoint Inhibitor

Nivolumab-relatlimab Combo for Colorectal Cancer (RELATIVITY-123 Trial)

Phase 3

Waitlist Available

Research Sponsored by Bristol-Myers Squibb

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Histological confirmed previously treated colorectal cancer with adenocarcinoma histology with metastatic or recurrent unresectable disease at study entry

Must have sufficient tumor tissue & evaluable PD-L1 expression to meet the study requirements

Must not have

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

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to follow up visit 2 (approximately 135 days after last dose)

Awards & highlights

No Placebo-Only Group

Pivotal Trial

Summary

This trial is testing a combination of two drugs, relatlimab and nivolumab, for patients with a certain type of colorectal cancer who haven't responded to other treatments. The drugs help the immune system attack the cancer.

Who is the study for?

This trial is for adults with metastatic colorectal cancer that's not microsatellite instability high (MSI-H)/deficient mismatch repair (dMMR). They must have tried 1-4 standard treatments including specific chemotherapy and targeted drugs, depending on their genetic makeup. People can't join if they've had certain heart issues, untreated brain metastases, prior immunotherapy or the study drugs Regorafenib/TAS-102.

What is being tested?

The study tests a fixed-dose combination of two immune checkpoint inhibitors, Nivolumab-relatlimab FDC (BMS-986213), against either Regorafenib or TAS-102 in patients who have previously treated metastatic colorectal cancer. It aims to see which treatment is more effective after other therapies have failed.

What are the potential side effects?

Nivolumab-relatlimab may cause immune-related side effects like inflammation in various organs, skin reactions, hormone gland problems (like thyroid dysfunction), and flu-like symptoms. Regorafenib and TAS-102 might cause fatigue, hand-foot syndrome, diarrhea, liver function changes among others.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

Select...

My colorectal cancer, which cannot be surgically removed, has returned or spread.

Select...

My cancer has enough tissue for testing and shows PD-L1 activity.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

Select...

I do not have uncontrolled high blood pressure, recent heart issues, severe lung disease, or active autoimmune disease.

Select...

My tumor is confirmed to be MSI-H/dMMR.

Select...

I have previously been treated with immunotherapy, regorafenib, or TAS-102.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to follow up visit 2 (approximately 135 days after last dose)

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to follow up visit 2 (approximately 135 days after last dose)

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to follow up visit 2 (approximately 135 days after last dose) for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Secondary study objectives

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 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

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

Trial Design

2Treatment groups

Experimental Treatment

Active Control

Group I: Arm A: Nivolumab + Relatlimab Fixed-dose Combination (FDC)Experimental Treatment1 Intervention

Group II: Arm B: Investigator's ChoiceActive Control2 Interventions

Treatment with Regorafenib or TAS-102

0 / 5Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for colorectal cancer, particularly immune checkpoint inhibitors like Relatlimab and Nivolumab, work by targeting proteins that regulate the immune system's ability to attack cancer cells. Relatlimab inhibits LAG-3, a protein that suppresses T-cell activity, while Nivolumab blocks PD-1, another protein that downregulates immune responses. By inhibiting these proteins, these drugs enhance the immune system's ability to recognize and destroy cancer cells, offering a promising treatment option for patients who have not responded to traditional therapies.

Is There Still Room for Cancer Vaccines at the Era of Checkpoint Inhibitors.