Nivolumab-relatlimab Combo for Colorectal Cancer

(RELATIVITY-123 Trial)

Recruiting at 323 trial locations

Overseen By BMS Study Connect Contact Center www.BMSStudyConnect.com

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Bristol-Myers Squibb

Must not be taking: Immunotherapy, Regorafenib, TAS-102

Disqualifiers: Untreated CNS metastases, Refractory hypertension, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 2

Duration: Until disease progression or unacceptable toxicity

700 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, it does exclude those who have had prior treatment with certain immunotherapies, regorafenib, or TAS-102.

What data supports the effectiveness of the drug Nivolumab-relatlimab FDC, Regorafenib, Stivarga, Regorafenib, BAY 73-4506, Regonix, TAS-102, Trifluridine/tipiracil hydrochloride mixture, TAS-102, Lonsurf for colorectal cancer?

Regorafenib and trifluridine/tipiracil (TAS-102) are approved for treating metastatic colorectal cancer and have shown modest improvements in survival compared to supportive care, based on the RECOURSE and CORRECT trials. ^{1 2 3 4 5}

Is the Nivolumab-relatlimab combo generally safe for humans?

The safety data for regorafenib and trifluridine/tipiracil (TAS-102), which are used in treating metastatic colorectal cancer, show that adverse events (side effects) are generally manageable and tolerable. These drugs have been used safely in patients, although side effects are common. ^{1 2 3 5 6}

What makes the Nivolumab-relatlimab combo unique for colorectal cancer treatment?

The Nivolumab-relatlimab combo is unique because it combines immunotherapy (using the body's immune system to fight cancer) with targeted therapies like regorafenib and TAS-102, which are used for patients whose cancer has not responded to standard chemotherapy. This combination aims to enhance the effectiveness of treatment by using different mechanisms to attack the cancer. ^{2 3 4 6 7}

Research Team

Bristol-Myers Squibb

Principal Investigator

Bristol-Myers Squibb

Eligibility Criteria

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.

Inclusion Criteria

My cancer worsened within 3 months after my last standard treatment.

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

I had severe side effects from previous chemotherapy despite support.

Exclusion Criteria

Other protocol-defined Inclusion/Exclusion criteria apply

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

I have had treatment for brain metastases and my neurological function is back to normal.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either the nivolumab-relatlimab fixed-dose combination or treatment with Regorafenib or TAS-102

Until disease progression or unacceptable toxicity

Follow-up

Participants are monitored for safety and effectiveness after treatment

Approximately 135 days after last dose

Up to follow-up visit 2

Treatment Details

Interventions

• Nivolumab-relatlimab FDC
• Regorafenib
• TAS-102

Trial Overview 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.

Participant Groups

Group I: Arm A: Nivolumab + Relatlimab Fixed-dose Combination (FDC) Experimental Treatment 1 Intervention

Group II: Arm B: Investigator's Choice Active Control 2 Interventions

Treatment with Regorafenib or TAS-102

Who Is Running the Clinical Trial?

Bristol-Myers Squibb

Lead Sponsor

Trials

2,731

Recruited

4,127,000+

Headquarters

New York City, USA

Known For

Oncology & Cardiovascular

Top Products

Eliquis, Opdivo, Revlimid, Orencia

Christopher Boerner

Bristol-Myers Squibb

Chief Executive Officer since 2023

PhD in Business Administration from the Haas School of Business, University of California, Berkeley; BA in Economics and History from Washington University in St. Louis

Deepak L. Bhatt

Bristol-Myers Squibb

Chief Medical Officer since 2024

MD from Yale University; MSc in Clinical Epidemiology from the University of Pennsylvania

Findings from Research

In a study of 72 patients with microsatellite stable metastatic colorectal cancer, regorafenib or fruquintinib combined with sintilimab showed a median progression-free survival of 4.2 months and an overall survival of 10.5 months, indicating these combinations are viable third-line treatment options.

The treatment was generally well-tolerated, with only 15.3% of patients experiencing severe adverse events, and patients without liver metastasis showed better response rates and overall survival, suggesting they may benefit more from this regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Microsatellite stable metastatic colorectal cancer without liver metastasis may be preferred population for regorafenib or fruquintinib plus sintilimab as third-line or above therapy:A real-world study. Nie, C., Lv, H., Chen, B., et al.[2022]

References

1. United States pubmed.ncbi.nlm.nih.gov

A Real-World Comparison of Regorafenib and Trifluridine/Tipiracil in Refractory Metastatic Colorectal Cancer in the United States. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

Regorafenib Versus Trifluridine/Tipiracil for Refractory Metastatic Colorectal Cancer: A Retrospective Comparison. [2022]

3. Switzerland pubmed.ncbi.nlm.nih.gov

An Observational Study of Trifluridine/Tipiracil-Containing Regimen Versus Regorafenib-Containing Regimen in Patients With Metastatic Colorectal Cancer. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

TK-1, TP, Ang-2, and Tie-2 mRNA expression in plasma-derived microvesicles of chemo-refractory metastatic colorectal cancer patients. [2023]

5. New Zealand pubmed.ncbi.nlm.nih.gov

Emerging combination therapies for metastatic colorectal cancer - impact of trifluridine/tipiracil. [2020]

6. Greece pubmed.ncbi.nlm.nih.gov

Retrospective study of regorafenib and trifluridine/tipiracil efficacy as a third-line or later chemotherapy regimen for refractory metastatic colorectal cancer. [2020]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Microsatellite stable metastatic colorectal cancer without liver metastasis may be preferred population for regorafenib or fruquintinib plus sintilimab as third-line or above therapy:A real-world study. [2022]