Nivolumab (Anti-Programmed Death-1 [PD-1]; BMS-936558) in Patients (PTS) with Advanced Solid Tumors: Clinical Activity, Safety, and Molecular Markers

Abstract

Background: Blockade of PD-1, a co-inhibitory receptor expressed by activated T cells, can overcome immune resistance and mediate tumor regression. This phase 1 study describes the activity and safety of nivolumab, an anti-PD-1 monoclonal antibody, in pts with advanced cancers. Methods: Pts received nivolumab IV q2wk at 0.1 - 10 mg/kg during dose escalation and/or cohort expansion. Tumors were assessed by RECIST v1.0. Pts received ≤12 cycles (4 doses/cycle) or until treatment discontinuation criteria were met. Results: As of July 3, 2012, 304 pts with melanoma (MEL, n = 107), non-small cell lung (NSCLC, n = 127), renal cell (RCC, n = 34), colorectal (CRC, n = 19), and prostate (n = 17) cancer were treated. MTD was not reached. Grade 3 drug-related AEs occurred in 15% of pts. The most common drug-related AEs (any grade; were rash (14%), diarrhea (12%), and pruritus (10%). There were 3 deaths due to pneumonitis (2 NSCLC, 1 CRC). In evaluable pts, objective responses (ORs) or prolonged stable disease was observed in MEL, RCC, and NSCLC (Table). In addition, some pts had a persistent reduction in overall tumor burden in the presence of new lesions and were not categorized as responders. To assess PD-1 ligand (PD-L1) as a potential predictive molecular marker, immunohistochemistry was performed on pretreatment tumor biopsies from 42 pts. Of 25 pts with PD-L1(+) tumors, 9 (36%) achieved OR vs 0/17 with PD-L1(-). Conclusions: Nivolumab produces durable activity in advanced NSCLC, MEL, and RCC. Preliminary data suggest a relationship between PD-L1 expression status on tumor cells and OR.