453P - Anti-Programmed Death-1 (PD-1) (BMS-936558/MDX-1106/ONO-4538) in Patients (PTS) with Advanced Solid Tumors: Clinical Activity, Safety, and Molecular Markers

Abstract

ABSTRACT Purpose Blockade of PD-1, a co-inhibitory receptor expressed by activated T cells, can overcome immune resistance and mediate tumor regression. This study describes the activity and safety of BMS-936558, an anti-PD-1 monoclonal antibody, in pts with advanced cancers. Methods Pts received BMS-936558 IV q2wk at 0.1 - 10 mg/kg during dose escalation and/or cohort expansion. Tumors were assessed by RECIST v1.0. Pts received up to 12 cycles (4 doses/cycle) or until unacceptable toxicity, confirmed progressive disease, or complete response. Results As of Feb 24, 2012, 296 pts with melanoma (MEL, n = 104), non-small cell lung (NSCLC, n = 122), renal cell (RCC, n = 34), colorectal (n = 19), and prostate (n = 17) cancer were treated. Median duration of therapy was 16 wks (range 2.0 - 121.7 wks). MTD was not reached. Grade ≥3 drug-related AEs occurred in 14% of pts. AEs of special interest included pneumonitis, vitiligo, colitis, hepatitis, hypophysitis, and thyroiditis. There were 3 deaths due to pneumonitis. In evaluable pts, objective responses (ORs) or prolonged stable disease was observed in MEL, RCC, and NSCLC (Table). Some 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 BMS-936558 produces durable activity in advanced NSCLC, MEL, and RCC, supporting further clinical development. Preliminary data suggest a relationship between PD-L1 expression status on tumor cells and OR. Additional long-term follow-up data will be reported. Tumor type Dose, mg/kg No. pts a ORR, No. pts (%) [95% CI] SD ≥24 wks, No. pts (%) [95% CI] PFSR at 24 wks, % [95% CI] MEL 0.1 - 10 94 26 (28) * [19 - 38] 6 (6) [2 - 13] 41 [30 - 51] NSCLC 1 - 10 76 14 (18) [11 - 29] 5 (7) [2 - 15] 26 [16 - 36] RCC 1 - 10 33 9 (27) * [13 - 46] 9 (27) [13 - 46] 56 [39 - 73] a Response-evaluable pts dosed by 07/01/2011 * 1 CR ORR = objective response rate ([{CR + PR} ÷ n] × 100); PFSR = progression-free survival rate; SD = stable disease Disclosure S.L. Topalian: Consultant/Advisory Role: Bristol-Myers Squibb (myself, uncompensated); Amplimmune Inc (immediate family member, compensated). Research Funding: Bristol-Myers Squibb. F.S. Hodi: Consultant or Advisory Role: Bristol-Myers Squibb (myself, uncompensated). Research Funding: Bristol-Myers Squibb (myself). D.F. McDermott: Advisory Board Role: Bristol-Myers Squibb (Ad board participation). D.C. Smith: Research Funding: BMS Oncology (myself). J.M. Taube: Research Funding: Bristol-Myers Squibb (myself). A. Gupta: Employment or Leadership Role: Bristol-Myers Squibb (employment, myself, compensated). Stock Ownership: Bristol-Myers Squibb (myself). J.M. Wigginton: Employment or Leadership Role: Bristol-Myers Squibb (employment, myself, compensated). Stock Ownership: Bristol-Myers Squibb (myself). M. Sznol: Consultant or Advisory Role: Bristol-Myers Squibb (myself, compensated). Research Funding: Bristol-Myers Squibb (clinical trial funding, myself). All other authors have declared no conflicts of interest.