1. Intervista a Lucio Crinò
Phase II studies of Nivolumab in patients with Advanced Squamous (SQ) or Non-Squamous (NSQ) Non-Small Cell Lung Cancer (NSCLC)
Intervista a Lucio Crinò

2. Background: Programmed death 1 (PD-1) is an immune checkpoint that suppresses antitumor immunity. Nivolumab (ONO-4538, BMS ), a fully human IgG4, anti-PD-1 antibody, has shown durable clinical activity in previous phase I and II trials in several tumor types. In March 2015, U.S. Food and Drug Administration (FDA) has approved Nivolumab injection for the treatment of patients with metastatic squamous (SQ) non-small cell lung cancer (NSCLC) with progression on or after platinum-based chemotherapy. Here, we report the results of two phase II studies to evaluate the efficacy and safety of nivolumab in previously treated advanced SQ (JapicCTI-No ) and NSQ (JapicCTI-No ) NSCLC pts in Japan. Material and Methods: Both studies required pts aged ≥20 years with an ECOG performance status of 0 or 1, stage IIIB/IV, or recurrent NSCLC and at least one prior chemotherapy including platinum containing regimen. Pts received nivolumab 3mg/kg IV Q2W until disease progression or unacceptable toxicity. The primary endpoint in both studies was the objective response rate (ORR) (RECIST v1.1). Planned sample size was 30 pts for SQ and 67 pts for NSQ (P0=0.09 & P1=0.26, P0=0.09 & P1=0.20; α=0.025 (one-side), 1-β=0.8). Results: From April 2013 to April 2014, a total of 111 NSCLC pts were enrolled in both studies (35 pts with SQ and 76 pts with NSQ). Baseline characteristics were collected and combined across both studies. Patients had a median age of 65 years (range 31 to 84), male/female were 81/30, ECOG PS 0/1 was 46/55 and Stage IIIB/Stage IV/recurrence was 6/86/19. Objective response rates were 25.7% (95%CI: 14.2, 42.1) in SQ and 19.7% (95%CI: 12.3, 30.0) in NSQ pts. Complete Response was observed in 2.6% with NSQ. Median progression-free survival was 4.2 (95%CI: 1.4, 7.1) for SQ and 2.8 months (95%CI: 1.4, 3.4) for NSQ. Median follow-up time was 10.4 and 8.4 months, respectively. Median duration of response was not reached in either study. Of 9 SQ pts and 15 NSQ pts who responded to nivolumab, durable and ongoing response was observed in 77.8% (7/9) and 80.0% (12/15), respectively. Median overall survival was not reached in either study. All Grade treatment-related adverse events across both studies were 79.3% (88/111) and Grade 3–4 treatment related adverse events (G3–4 AEs) were observed in 16.2% of pts. Most common G3–4 AEs were lymphocyte count decreased (3.6%), hyponatremia (1.8%), interstitial lung disease (1.8%), and pleural effusion (1.8%). Any grade of interstitial lung disease was observed in 4.5% of pts. No grade 5 AEs were observed. Conclusions: In both SQ and NSQ NSCLC pts from Japan, nivolumab showed encouraging clinical efficacy and safety profile that was consistent with data from the previous phase I and II studies with a manageable safety profile.