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Tumors with high TMB responded well to combination in large patient population.

By now the results of the phase III CheckMate-227 study are known by most. The primary endpoint of progression-free survival was met, and the immunotherapy (IO) combination of nivolumab and ipilimumab was proven superior to chemotherapy in the first line for patients with NSCLC and high tumor mutation burden (TMB; ≥ 10 mutations/megabase, mut/mb), regardless of PD-L1 expression status. Approximately 45% of evaluable patients had tumors with high TMB, which was evaluated using the FoundationOne CDx assay. The safety profile was consistent with previously reported studies of 3 mg/ kg of nivolumab administered every 2 weeks and 1 mg/kg of ipilimumab given every 6 weeks.

CheckMate-227 enrolled more than 2,500 patients with squamous and nonsquamous histologies. There are three parts to the study, with PFS reported for all of Part 1. Part 1a evaluated combination nivolumab and ipilimumab vs. nivolumab alone vs. chemotherapy in patients whose tumors express PD-L1. Part 1B evaluated the IO combination vs. nivolumab plus chemotherapy vs. chemotherapy alone in patients whose tumors do not express PD-L1. Part 2 evaluates nivolumab combined with chemotherapy vs. chemotherapy alone in a broad population; the primary endpoint is overall survival. ✦

(For more on TMB, see the interview with Dr. Solange Peters)

Editor’s Note

The results of this study, as reported in the recent press release, are tantalizing. It propels the role of TMB into the forefront. Assuming an overall survival advantage emerges, it is possible that immunotherapy combinations may start to replace empiric combinations of chemotherapy and checkpoint inhibitors in treatment-naive, advanced NSCLC, regardless of PD-L1 status, although this remains speculative. –Corey Langer, MD, Editor