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
|
Abstract
PurposeBMS-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.
MethodsBMS-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.
ResultsAs 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.
ConclusionsBMS-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
DisclosureL. 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.