Nivolumab (Anti-Pd-1; Bms-936558, Ono-4538) in Combination with Platinum-Based Doublet Chemotherapy (Pt-Dc) or Erlotinib (Erl) in Advanced Non-Small Cell Lung Cancer (Nsclc)

Abstract

ABSTRACT Aim: We report interim data from a phase 1 study of nivolumab (N), a fully human IgG4 programmed death-1 (PD-1) immune checkpoint inhibitor antibody, combined with PT-DC or ERL in advanced chemotherapy-naive NSCLC patients (pts). Methods: Pts (n = 56) were assigned by histology to receive N 10 mg/kg IV Q3W + concurrent IV gemcitabine 1250 mg/m2 + cisplatin 75 mg/m2 (squamous [sq]) or pemetrexed 500 mg/m2 + cisplatin 75 mg/m2 (non-sq), or N 5 or 10 mg/kg IV Q3W + IV paclitaxel 200 mg/m2 + carboplatin AUC6 (sq + non-sq). N + PT-DC was given for 4 cycles, with continued N to progression/unacceptable toxicity. EGFR mutant (EGFR MT) NSCLC pts (n = 21) received N 3 mg/kg IV Q2W + ERL 150 mg PO daily until progression/unacceptable toxicity. Objective response rate (ORR) was assessed by RECIST 1.1. Results: Across N + PT-DC arms (median follow-up [mF/U] 75 wks), grade 3–4 related AEs occurred in 45% of pts (25–73% across arms); 4 pts (7%) had grade 3–4 pneumonitis; 0–33% discontinued due to related AEs, any-grade pneumonitis (7%) most common. ORR with N + PT-DC was 33–47%; PD as best overall response (BOR) was infrequent (7%). Progression-free survival (PFS) rate at wk 24 was 38–71%; 1-yr OS rate was 50–87%. With N + ERL (mF/U 72 wks), grade 3–4 related AEs occurred in 5 pts; no pneumonitis was observed. Related AEs led to discontinuation in 4 pts (grade 3 AST ↑, grade 3 diarrhea, grade 2 nephritis, grade 2 flushing). ORR was 19% (median duration of response [DOR] not reached; range 60.1, 72.3+ wks); 24-wk PFS rate was 51%. Three of 20 pts (15%) with acquired ERL resistance achieved PR (DOR 60.1, 64.6 + , 70+ wks; 2 ongoing); 9/20 pts had BOR of SD, with 3/9 not progressed (time to progression/death 9.9+–53 wks); 1 pt had an ongoing unconventional response. One pt was EGFR TKI naive and achieved PR (DOR 72.3+ wks; ongoing). Conclusions: N + PT-DC demonstrated acceptable antitumor activity and safety reflecting additive nivolumab and PT-DC toxicities in pts with advanced NSCLC. N + ERL may provide durable clinical benefit and an acceptable safety profile in TKI-refractory, EGFR MT pts. These data support further evaluation of nivolumab combination regimens in pts with advanced NSCLC. Disclosure: S. Gettinger: Consultant advisor BMS; Honoraria for BMS advisory board; N. Rizvi: Consultant Advisor-BMS; Honoraria-BMS, Medimmune, Genentech/Roche; L.Q. Chow: BMS Stock; Research Funding-Bristol-Myers Squibb funding goes to University of Washington; H. Borghaei: Consultant advisor-Genentech, BMS; Research Funding- Pfizer, Arisaph, Millenium; Honoraria-Genentech; J.R. Brahmer: Consultant advisor BMS; Stock BMS; Research Funding BMS; R. Juergens: Research funding BMS; F.A. Shepherd: Consultant advisor (compensated), honoraria-BMS; J. Goldman: Research funding-BMS, Genentech; Y. Shen: BMS Employee; BMS Stock; C. Harbison: BMS-employee, stock; A. Chen: BMS-employee, stock; S.J. Antonia: Consultant advisor, honoraria, research funding for BMS MedImmune provides funding for clinical trials. All other authors have declared no conflicts of interest.