RELATIVITY-123 MSS CRC unlikely to reach primary endpoint and will be discontinued

Other trials evaluating fixed-dose combinations of nivolumab and leratorimab as treatments for other tumor types will continue.

The phase 3 RELATIVITY-123 trial (NCT05328908) tested nivolumab (Opdivo) and relatlimab (Opdurag) in patients with microsatellite stable (MSS) metastatic colorectal cancer (mCRC) who had disease progression after 1 to 4 days. ) is evaluating the effectiveness of combination therapy. Previous treatments for metastatic disease will be discontinued due to futility, according to a news release from Bristol-Myers Squibb, the drug’s developer.¹

The discontinuation was based on an evaluation by an independent data monitoring committee, which determined that the trial met the common endpoint of overall survival (OS) in all randomized patients and in randomized patients with PD-L1 conjugate positivity. judged to be unlikely to be achieved. Score of at least 1 on completion (CPS).

The cancellation was not based on safety concerns. The safety profile was consistent with previous studies evaluating a fixed-dose combination of nivolumab and leratlimab.

“Metastatic colorectal cancer is a cancer with high unmet need and is difficult to treat. Progress has been made in the treatment of patients with microsatellite instability-high (MSI-H)/mismatch repair deficient (dMMR) colorectal cancer. However, treatment options remain limited for subsequent treatment of patients with microsatellite stable (MSS) tumors,” Jeffrey said. Walch, M.D., vice president and global program leader at Bristol-Myers Squibb, said in a news release. “Historically, we know that the efficacy of immunotherapy for MSS colorectal cancer has been limited, but we had hoped to demonstrate meaningful clinical benefit in this patient population; We are disappointed with the results. We will continue to work hard on the development. [immuno]Treatments such as nivolumab and ipilimumab [Yervoy]We would like to thank the MSI-H/dMMR colorectal cancer study and thank the researchers, patients, and their loved ones who participated in this trial. ”

This randomized, open-label trial evaluated nivolumab and leratorimab compared with regorafenib (Stivarga) or TAS-102 (trifluridine/tipiracil; Lonsurf) in patients with late-stage non-MSI-H/dMMR mCRC. was aimed at.² Participation in this study was based on recent progression on 1 to 4 prior lines of therapy, ECOG performance status of 0 or 1, and measurable disease according to RECIST v1.1 criteria. subject to certain conditions. Patients with confirmed MSI-H/dMMR disease, prior treatment with immunotherapy, regorafenib or TAS-102, and/or significant cardiovascular disease, interstitial lung disease/pneumonia, or autoimmune disease. Patients with a history of were excluded from the study.

Secondary endpoints of this study included overall response rate (ORR), progression-free survival (PFS), duration of response as assessed by a blinded independent central review and investigators according to RECIST v1.1 criteria; Includes safety and time to definitive deterioration. Physical function and quality of life for all randomized patients and those with PD-L1 CPS ≥1.

For patients currently enrolled in the RELATIVITY-123 trial, next steps will be determined. Data will be shared with other researchers. Other trials evaluating fixed-dose combinations of nivolumab and leratorimab as treatments for other tumor types will continue. Bristol-Myers Squibb noted that these results do not affect the approval of nivolumab and leratlimab as combination therapy for patients with unresectable or metastatic melanoma.³

References

1. Bristol-Myers Squibb provides an update on the RELATIVITY-123 study evaluating fixed-dose combination therapy of nivolumab and leratolimab in patients with previously treated metastatic microsatellite stable (MSS) colorectal cancer. news release. Bristol-Myers Squibb Company. December 15, 2023. Accessed December 18, 2023. https://tinyurl.com/yvyv84rj
2. Feeney K, Joubert WL, Bordoni RE, et al. RELATIVITY-123: Nivolumab (NIVO) + relatlimab (RELA) fixed-dose combination therapy (FDC) with regorafenib or trifluridine + tipiracil (TAS-) for late-stage metastatic colorectal cancer. 102) Phase 3 randomized, open-label trial (mCRC). J Clin Oncor. 2023;41(4_suppl):TPS278-TPS278. doi:10.1200/jco.2023.41.4_suppl.tps278
3. The FDA has approved Opdurag for unresectable or metastatic melanoma. news release. F.D.A. March 18, 2022. Accessed December 19, 2023. https://tinyurl.com/cwbnkbkm