Overall Survival and Response with Nivolumab and Relatlimab in Advanced Melanoma.

BACKGROUND: A phase 2/3 trial ­ A Study of Relatlimab Plus Nivolumab Versus Nivolumab Alone in Participants With Advanced Melanoma (RELATIVITY-047) ­ evaluated nivolumab + relatlimab as a fixed-dose combination and found a significant progression-free survival (PFS) benefit over nivolumab monotherapy in previously untreated unresectable or metastatic melanoma. We now report updated PFS and safety data and the first results for overall survival (OS) and objective response rate (ORR). METHODS: Patients were randomly assigned 1:1 to receive nivolumab 480 mg and relatlimab 160 mg fixed-dose combination or nivolumab 480 mg alone, given intravenously every 4 weeks. PFS (primary end point) according to the Response Evaluation Criteria in Solid Tumors, version 1.1, was assessed by blinded independent central review (BICR). Secondary end points, tested hierarchically, were OS and then ORR per Response Evaluation Criteria in Solid Tumors, version 1.1, per BICR. RESULTS: At a median follow-up of 19.3 months, median PFS according to BICR was 10.2 months (95% confidence interval [CI], 6.5 to 14.8) with nivolumab + relatlimab versus 4.6 months (95% CI, 3.5 to 6.4) with nivolumab (hazard ratio, 0.78; 95% CI, 0.64 to 0.94). Median OS was not reached (NR) (95% CI, 34.2 to NR) with nivolumab + relatlimab versus 34.1 months (95% CI, 25.2 to NR) with nivolumab (hazard ratio, 0.80; 95% CI, 0.64 to 1.01; P=0.059) (prespecified value for statistical significance, P≤0.043). ORRs per BICR were 43.1% (95% CI, 37.9 to 48.4) versus 32.6% (95% CI, 27.8 to 37.7), respectively. Grade 3/4 treatment-related adverse events were observed in 21.1% of patients treated with nivolumab + relatlimab versus 11.1% treated with nivolumab. CONCLUSIONS: The fixed-dose combination of nivolumab + relatlimab showed consistent PFS benefit versus nivolumab with approximately 6 months of additional median follow-up. The combination treatment did not reach the preplanned statistical threshold for OS, with a 10.3 percentage-point difference in ORR. Grade 3/4 treatment-related adverse events were more frequent with nivolumab + relatlimab versus nivolumab. (Funded by Bristol Myers Squibb; ClinicalTrials.gov number, NCT03470922.)

Informatics-guided procurement of patient samples for biomarker discovery projects in cancer research.

Modern cancer research for biomarker discovery program requires solving several tasks that are directly involved with patient sample procurement. One requirement is to construct a highly efficient workflow on the clinical side for the procurement to generate a consistent supply of high quality samples for research. This undertaking needs a network of interdepartmental collaborations and participations at various levels, including physical human interactions, information technology implementations and a bioinformatics tool that is highly effective and user-friendly to busy clinicians and researchers associated with the sample procurement. Collegial participation that is sequential but continual from one department to another demands dedicated bioinformatics software coordinating between the institutional clinic and the tissue repository facility. Participants in the process include admissions, consenting process, phlebotomy, surgery center and pathology. During this multiple step procedures, clinical data are collected for detailed analytical endpoints to supplement logistics of defining and validating the discovery of biomarkers.