Safety and Efficacy Results of a Phase I, Open-Label Study of Concurrent and Delayed Nivolumab in Combination With -Paclitaxel and Carboplatin in Advanced Non-small Cell Lung Cancer.

Multicenter, phase I study of concurrent and delayed nivolumab plus -paclitaxel/carboplatin in advanced non-small cell lung cancer (NSCLC). Chemotherapy-naive patients with advanced NSCLC (ineligible for potentially curative radiation or surgery) received -paclitaxel 100 mg/m (days 1, 8, 15) and carboplatin area under the curve 6 (day 1) intravenously every 21 days (first 4 cycles); nivolumab 5 mg/kg was administered intravenously (day 15) beginning in cycle 1 (concurrent) or cycle 3 (delayed) in separate cohorts and continued beyond the 4 chemotherapy cycles. The primary objective was to assess safety. Secondary objectives were to assess tolerability and explore antitumor activity. All 32 patients received chemotherapy; 20 of 22 and 6 of 10 patients also received concurrent or delayed nivolumab, respectively. No dose-limiting toxicities were reported in the concurrent cohort; 1 dose-limiting toxicity was reported in the delayed cohort. In the concurrent cohort, 20 patients (91%) had ≥1 grade 3/4 treatment-emergent adverse event (TEAE), and 7 (32%) discontinued treatment due to TEAEs. In the delayed cohort, all patients had ≥1 grade 3/4 TEAE, and 2 (20%) discontinued due to TEAEs. The median progression-free and overall survival, respectively, were 10.5 and 29.3 months in the concurrent cohort and 4.1 and 8.2 months in the delayed cohort. The safety profile of the combination was consistent with that of individual agents and generally similar in the 2 cohorts. Efficacy outcomes in the concurrent cohort, but not in the delayed cohort, were encouraging and support the rationale for concurrent administration of nivolumab with -paclitaxel/carboplatin for the treatment of advanced NSCLC. www.ClinicalTrials.gov, identifier: NCT02309177.