1237PD - Clinical activity and safety of anti-programmed death-1 (PD-1) (BMS-936558/MDX-1106/ONO-4538) in patients (pts) with advanced non-small cell lung ca...

Date 29 September 2012
Event ESMO Congress 2012
Session NSCLC - Immunotherapy, SCLC and Mesothelioma
Topics Non-Small-Cell Lung Cancer, Metastatic
Cancer Immunology and Immunotherapy
Presenter Scott Gettinger
Authors S. Gettinger1, L. Horn2, S.J. Antonia3, D.R. Spigel4, L. Gandhi5, L.V. Sequist6, J.M. Wigginton7, G. Kollia8, A. Gupta9, J.R. Brahmer10
  • 1Thoracic Oncology Program, Yale University School of Medicine, New Haven/US
  • 2Thoracic Oncology Program, Vanderbilt-Ingram Cancer Center, Nashville/US
  • 3Thoracic Oncology, H. Lee Moffitt Cancer Center & Research Institute, Tampa/US
  • 4Sarah Cannon Research Institute/Tennessee Oncology PLLC, Nashville/US
  • 5Oncology, Dana-Farber Cancer Institute, Boston/US
  • 6Oncology, Massachusetts General Hospital Cancer Center, Boston/US
  • 7Discovery Medicine-clinical Oncology, Bristol-Myers Squibb, Princeton/US
  • 8Biostatistics And Data Management, Bristol-Myers Squibb, Princeton/US
  • 9Discovery Medicine, Immuno-oncology, Bristol-Myers Squibb, Princeton/US
  • 10Sidney Kimmel Cancer Center at Johns Hopkins University, Baltimore/US

Abstract

Purpose

BMS-936558 is a fully human monoclonal antibody that blocks the PD-1 co-inhibitory receptor expressed by activated T cells. We report here the activity and safety of BMS-936558 in pretreated pts with advanced NSCLC, a tumor not previously considered responsive to immunotherapy.

Methods

BMS-936558 was administered IV q2wk to pts with various solid tumors at 1 − 10 mg/kg during dose escalation and/or cohort expansion. Pts with advanced NSCLC previously treated with at least 1 prior line of therapy were eligible. Pts received up to 12 cycles (4 doses/cycle) of treatment or until unacceptable toxicity, confirmed progressive disease, or complete response. Clinical activity was assessed by RECIST v1.0.

Results

As of Feb 24, 2012, 122 NSCLC pts had received BMS-936558 at 1 (n = 31), 3 (n = 33), or 10 mg/kg (n = 58). ECOG performance status was ≤1 for 117/122 pts; 67/122 pts had received ≥3 prior therapies. Median duration of therapy was 12 weeks (range 2 − 101.3 wks). Common drug-related AEs in NSCLC pts were fatigue (18%), decreased appetite (10%), anemia (8%), and nausea (7%). The incidence of grade 3–4 related AEs was 8%. There were 2 drug-related deaths from pneumonitis. Of 76 evaluable pts, 14 had a partial response (PR) (Table); all 14 were treated ≥24 wk, and 8 had responses of ≥24 wk. 5 Five pts had stable disease (SD) lasting ≥24 wk. Additionally, 3 pts had a persistent decrease in target lesion tumor burden in the presence of new lesions and were not categorized as responders.

Conclusions

BMS-936558 had an acceptable risk: benefit profile in previously treated, advanced NSCLC. Activity in squamous NSCLC was particularly intriguing. Additional long-term follow-up data will be reported.

Dose, mg/kg No. ptsa ORR,No. pts (%)[95% CI] PFSR at24 wks, %[95% CI]
1 18 1 (6) [0.1 − 27] 16 [0 − 34]
3 19 6 (32) [13 − 57] 41 [18 − 64]
10 39 7 (18) [8 − 34] 24 [11 − 38]
All 76b 14 (18) [11 − 29] 26 [16 − 36]
All–Nonsquamous 56 7 (13) [5 − 24] 22 [11 − 34]
All–Squamous 18 6 (33) [13 − 59] 33 [12 − 55]

aResponse-evaluable pts dosed by 07/01/2011 bIncludes 2 pts with unknown histology, 1 with PR ORR = objective response rate ([{CR + PR} ÷ n] × 100); PFSR = progression-free survival rate

Disclosure

L. Horn: Consultant or Advisory Role: OSI/Astellas (myself, uncompensated).

D. Spigel: Consultant or Advisory Role: Bristol-Myers Squibb (myself, uncompensated).

L.V. Sequist: Consultant or Advisory Role: Clovis, Celgene, GlaxoSmithKline (myself, compensated); Daiichi-Sankyo, Merrimack (myself, uncompensated).

J.M. Wigginton: Employment or Leadership Role: Bristol-Myers Squibb (employment, myself, compensated). Stock Ownership: Bristol-Myers Squibb (myself).

G. Kollia: Employment or Leadership Role: Bristol-Myers Squibb (employment, myself, compensated). Stock Ownership: Bristol-Myers Squibb (myself).

A. Gupta: Employment or Leadership Role: Bristol-Myers Squibb (employment, myself, compensated). Stock Ownership: Bristol-Myers Squibb (myself).

All other authors have declared no conflicts of interest.