Futility Analysis Ends Nivolumab and Relatlimab Evaluation in Pretreated MSS mCRC

January 3, 2024

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The phase 3 RELATIVITY-123 trial evaluating the fixed-dose combination of nivolumab and relatlimab in patients with microsatellite stable metastatic colorectal cancer will be discontinued due to futility.

Jeffrey Walch, MD, PhD

The phase 3 RELATIVITY-123 trial (NCT05328908) will be discontinued due to futility. A planned analysis led by an independent data monitoring committee determined that the trial, which had been evaluating the fixed-dose combination of nivolumab and relatlimab (Opdualag) in patients with microsatellite stable (MSS) metastatic colorectal cancer (mCRC), was unlikely to meet its primary end points at study’s end.¹

The recommendation to stop the study was not due to safety issues, according to a news release issued by Bristol Myers Squibb. The safety profile of the regimen was consistent with prior reports of that of the fixed-dose combination. The decision to discontinue the trial will not affect other ongoing investigations of the regimen in other tumor types or the current approval for patients with unresectable or metastatic melanoma.²

The company is expected to conduct a full evaluation of the data and work with investigators to share the results with the scientific community and determine next steps for patients enrolled in the trial.

“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 [MSI-H]/deficient mismatch repair [dMMR] colorectal cancers, patients with MSS 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,” Jeffrey Walch, MD, PhD, vice president, global program lead, Bristol Myers Squibb, stated in a news release.¹

“We continue to be committed to the development of I-O therapies, including nivolumab [Opdivo] and ipilimumab [Yervoy], in MSI-H/dMMR colorectal cancers, and we thank the investigators, patients, and their loved ones who participated in this trial.”

The randomized, open-label, multicenter RELATIVITY-123 trial was designed to evaluate the fixed-dose combination of nivolumab and relatlimab compared with investigator’s choice of regorafenib (Stivarga) or trifluridine plus tipiracil (TAS-102; Lonsurf) in approximately 700 adult patients with MSS mCRC whose disease had progressed during or within approximately 3 months after at least 1 but no more than 4 prior lines of therapy in the metastatic setting.³

Additional eligibility criteria indicated that prior therapy in the absence of intolerance must have included a fluoropyrimidine, oxaliplatin, irinotecan, an anti-VEGF therapy, and anti-EGFR therapy if RAS wild-type if available. Adequate tumor tissue and evaluable PD-L1 expression as well as measurable disease were also required.

The dual primary end points of the study were overall survival in all randomized patients and in randomized patients with a PD-L1 combined positive score (CPS) of 1 or greater. Secondary end points included objective response rate, progression-free survival, and duration of response by blinded independent central review per RECIST v1.1 criteria, safety, and time until definitive deterioration-physical function and quality of life in all randomized patients and in randomized patients with PD-L1–positive tumors (CPS ≥ 1).