Nivolumab (anti-PD-1; BMS-936558, ONO-4538) in combination with platinum-based doublet chemotherapy (PT-DC) in advanced non-small cell lung cancer (NSCLC).

8113 Background: First-line PT-DC has demonstrated 1-yr overall survival (OS) rates of up to 54% in NSCLC; however, there remains a need for therapies with improved long-term survival. We report an updated analysis of a phase I multi-cohort study evaluating nivolumab, a fully human IgG4 programmed death-1 (PD-1) immune checkpoint inhibitor antibody, plus PT-DC in chemotherapy-naive patients (pts) with advanced NSCLC, with longer follow up and additional pts. Methods: Pts (N=56) with advanced NSCLC were assigned based on histology to 4 cohorts to receive nivolumab 10 mg/kg IV Q3W plus concurrent IV gemcitabine 1250 mg/m2 + cisplatin 75 mg/m2 (squamous sq) or pemetrexed 500 mg/m2 + cisplatin 75 mg/m2 (non-sq), or nivolumab 5 or 10 mg/kg IV Q3W plus IV paclitaxel 200 mg/m2+ carboplatin AUC6 (sq + non-sq), in a phase I dose de-escalation trial to assess dose-limiting toxicity (DLT). PT-DC was given for 4 cycles, followed by nivolumab until progression or unacceptable toxicity. Objective response rate (ORR) was assessed by RECIST 1.1. Results: No DLTs were seen during the first 6 wks of treatment. Grade 3-4 treatment-related adverse events were reported in 45% of pts (25-73% across arms), including pneumonitis (4 pts, 7%; managed by protocol algorithm), and fatigue and acute renal failure (3 pts 5% each). Across arms, ORR (≥10 months follow up) was 33–50% and progressive disease (PD) as best overall response (BOR) was infrequent (Table). One-year OS rates were 59–87% (Table). Conclusions: Nivolumab combined with standard PT-DC regimens used for first-line treatment of NSCLC demonstrated antitumor activity, with encouraging 1-yr OS and an acceptable tolerability profile. Clinical trial information: NCT01454102. Nivo 10 + gem/cis Sq Nivo 10 + pem/cis Non-sq Nivo 10 + pac/carb Sq + Non-sq Nivo 5 + pac/carb Sq + Non-sq N 12 15 15 14 ORR, a n (%) 4 (33) 7 (47) 7 (47) 7 (50) Median duration of response (Kaplan-Meier),a wk (range) 20.9 (12.1–41.7+) 32.0 (13.1–42.1+) 25.6 (11.4+–39.0+) Not reached (11.4–37.3+) PD as BOR, n (%) 0 0 3 (20) 1 (7) PFS rate wk 24, % 36 71 38 57 1-yr OS, % 59 87 59 Insufficient follow-up a Confirmed responses only. + Ongoing.