Nivolumab-relatlimab Combo for Colorectal Cancer

(RELATIVITY-123 Trial)

No longer recruiting at 352 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment combination for individuals with difficult-to-treat metastatic colorectal cancer, particularly for those whose cancer did not respond to other therapies. The trial evaluates whether a combination of two drugs, nivolumab and relatlimab (a fixed-dose combination), controls cancer more effectively than existing treatments like Regorafenib or TAS-102. It seeks participants with metastatic colorectal cancer who have tried up to four different treatments without success. For those whose cancer has continued to grow despite these treatments, this trial might be suitable. As a Phase 3 trial, this study represents the final step before FDA approval, offering access to potentially groundbreaking treatment.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the combination of nivolumab and relatlimab was well-tolerated in past studies. Patients in these studies experienced lasting positive effects and improved survival rates. Importantly, the safety of this combination matched expectations, with no new safety issues identified.

Regorafenib and TAS-102 are treatments already approved for certain types of cancer. While they can cause side effects, doctors generally know and manage these.

Overall, the safety information for these treatments suggests they are well-tolerated. However, discussing any concerns with a doctor is important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the nivolumab-relatlimab fixed-dose combination for colorectal cancer because it targets the immune system differently than standard chemotherapy and targeted therapies like bevacizumab or cetuximab. Nivolumab is an immune checkpoint inhibitor that blocks the PD-1 pathway, while relatlimab targets the LAG-3 pathway, potentially enhancing the immune response against cancer cells. This dual targeting approach could offer a new way to treat colorectal cancer, especially for patients who may not respond well to existing treatments. Additionally, with the option of regorafenib or TAS-102 as part of the investigational treatment, researchers are keen to see if combining or switching mechanisms can improve patient outcomes.

What evidence suggests that this trial's treatments could be effective for metastatic colorectal cancer?

Research has shown that the combination of nivolumab and relatlimab, which participants in this trial may receive, may help treat certain cancers. One study demonstrated improved outcomes for some patients with advanced colorectal cancer lacking a specific genetic marker called microsatellite instability. Nivolumab aids the immune system in fighting cancer cells, while relatlimab blocks a protein that can slow the immune response. Although not every study achieved its main goals, these treatments have shown potential in strengthening the body's natural defenses against cancer. This trial will compare the nivolumab-relatlimab combination with the investigator's choice of treatment, which includes Regorafenib or TAS-102, offering hope for its effectiveness in colorectal cancer. ^{1 5 6 7 8}

Who Is on the Research Team?

Bristol-Myers Squibb

Principal Investigator

Bristol-Myers Squibb

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05328908

NCT05328908 | A Study of Nivolumab-relatlimab Fixed ... The purpose of this study is to evaluate relatlimab in combination with nivolumab, administered as a fixed-dose combination (nivolumab-relatlimab FDC, ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.3554

A phase 2 study evaluating response and biomarkers in ... We conducted a phase 2 study of nivolumab (Nivo) (aPD1)/relatlimab (Rela) (aLAG3) in patients with previously treated advanced MSS CRC.

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40388545/

Nivolumab and Relatlimab for the Treatment of Patients with ... Conclusions: This investigation did not reach its primary endpoint for any of the three treatment cohorts but does provide critical insight into ...

4. asco.org asco.org/abstracts-presentations/ABSTRACT376412

OS and ORR by key subgroups from RELATIVITY-047. Background: In the phase 2/3 RELATIVITY-047 trial, NIVO + RELA as a fixed-dose combination (FDC) significantly improved the primary endpoint of ...

5. news.bms.com news.bms.com/news/details/2024/Bristol-Myers-Squibb-to-Present-Data-at-ESMO-Demonstrating-Ongoing-Leadership-in-Immuno-Oncology-and-Progression-of-Assets-from-Its-Differentiated-Research-Platforms/default.aspx

Bristol Myers Squibb to Present Data at ESMO ... Data from proof-of-concept, randomized, Phase 2 RELATIVITY-104 trial exploring the combination of nivolumab, relatlimab (1:1) and chemotherapy as first-line ...

6. news.bms.com news.bms.com/news/details/2023/Bristol-Myers-Squibb-Provides-Update-on-RELATIVITY-123-Trial-Evaluating-the-Fixed-Dose-Combination-of-Nivolumab-and-Relatlimab-in-Patients-with-Previously-Treated-Metastatic-Microsatellite-Stable-MSS-Colorectal-Cancer/default.aspx

Bristol Myers Squibb Provides Update on RELATIVITY-123 ... RELATIVITY-123 is a Phase 3 randomized, open label, multi-center trial evaluating the fixed-dose combination of nivolumab and relatlimab ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11149130/

Nivolumab plus relatlimab in patients with previously ... Nivolumab plus relatlimab demonstrated durable responses and survival benefit with a well-tolerated safety profile at 47.2-month median follow- ...

8. onclive.com onclive.com/view/futility-analysis-ends-nivolumab-and-relatlimab-evaluation-in-pretreated-mss-mcrc

Futility Analysis Ends Nivolumab and Relatlimab ... The safety profile of the regimen was consistent with prior reports of that of the fixed-dose combination. The decision to discontinue the trial ...