BMS Ends Phase 3 Trial of Nivolumab and Relatlimab in CRC
The phase 3 RELATIVITY-123 trial in metastatic microsatellite stable colorectal cancer is not expected to meet its primary end point upon completion and is being discontinued due to futility.
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Bristol Myers Squibb is ending the phase 3 RELATIVITY-123 trial (NCT05328908) investigating nivolumab (Opdivo) and relatlimab (Opdualag) in patients with previously treated metastatic microsatellite stable (MSS) colorectal cancer (CRC) with disease progression following 1, but no more than 4 lines of therapy, due to futility. The trial is not expected to meet its primary end point based on a planned analysis by an independent data monitoring committee, according to a press release.1
The safety profile was consistent with previously reported studies of the combination of nivolumab and relatlimab, and the trial was not discontinued due to safety concerns.
“Metastatic colorectal cancer is a challenging cancer to treat with high unmet needs. Though there have been advances in treating patients with microsatellite instability-high/deficient mismatch repair colorectal cancers, patients with microsatellite stable tumors continue to have limited treatment options in later lines of therapy. While we know immunotherapies have historically demonstrated limited efficacy in MSS colorectal cancers, we had hoped to demonstrate meaningful clinical benefit in this patient population and are disappointed in this outcome,” said Jeffrey Walch, MD, PhD vice president, global program lead, Bristol Myers Squibb, in a press release.
The primary end points of the study were overall survival (OS) in randomized patients with PD-L1 combined positive score (CPS) of 1 or more and OS in all randomized patients. The secondary end points included objective response rate (ORR) by blinded independent central review (BICR) in patients with PD-L1 CPS ≥ 1, ORR by BICR in all patients, progression-free survival (PFS) by BICR, duration of response (DOR) by BICR in patients with PD-L1 CPS ≥ 1, and DOR by BICR in all patients. The study was also evaluating safety by means of incidence of adverse events (AEs), serious AEs, immune-mediated AEs, and AEs leading to discontinuation.2
Patients in the experimental arm received a fixed-dose combination of nivolumab and relatlimab. Patients in the active comparator arm received regorafenib (Stivarga) or TAS-102 (Lonsurf).
In a prior study, the combination of nivolumab and relatlimab improved survival in patients with previously untreated melanoma. Findings come from the RELATIVITY-047 (NCT03470922) which were published in the New England Journal of Medicine. The nivolumab/relatlimab combination conferred a PFS of 10.1 months (95% CI, 6.4-15.7) compared with 4.6 months (95% CI, 3.4-5.6) with nivolumab alone (HR, 0.75; 95% CI, 0.62-0.92; P =.006). PFS at 12 months was 47.7% (95% CI, 41.8%-53.2%) with nivolumab and relatlimab vs 36.0% (95% CI, 30.5%-41.6%) with nivolumab alone.3
Based on this, the fixed-dose combination of nivolumab and relatlimab as a treatment for other tumor types will continue to be assessed. Results from the RELATIVITY-123 study do not impact the currently approved indication for patients with unresectable or metastatic melanoma.
“We continue to be committed to the development of [immune-oncology] therapies, including nivolumab and ipilimumab, in MSI-H/dMMR colorectal cancers, and we thank the investigators, patients, and their loved ones who participated in this trial,” said Walch, in the press release.1
