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...

Date 01 October 2012
Event ESMO Congress 2012
Session Poster presentation III
Topics Clinical Research
Basic Scientific Principles
Presenter Suzanne Topalian
Authors S.L. Topalian1, J.R. Brahmer2, F.S. Hodi3, D.F. McDermott4, D. Smith5, S. Gettinger6, J.M. Taube1, A. Gupta7, J.M. Wigginton8, M. Sznol9
  • 1Melanoma Program, Sidney Kimmel Cancer Center at Johns Hopkins University, Baltimore/US
  • 2Sidney Kimmel Cancer Center at Johns Hopkins University, Baltimore/US
  • 3Melanoma Program, Dana-Farber Cancer Institute, Boston/US
  • 4Division Of Hematology/oncology, Beth Israel Deaconess Medical Center, Boston/US
  • 5Division Of Hematology/oncology, Department Of Internal Medicine And Section Of Urology, Department Of Surgery, University of Michigan, Comprehensive Cancer and Geriatrics Center, Ann Arbor/US
  • 6Thoracic Oncology Program, Yale University School of Medicine, New Haven/US
  • 7Discovery Medicine, Immuno-oncology, Bristol-Myers Squibb, Princeton/US
  • 8Discovery Medicine-clinical Oncology, Bristol-Myers Squibb, Inc., Princeton/US
  • 9Section Of Medical Oncology, Yale University School of Medicine, New Haven/US



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.


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.


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(-).


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. ptsa 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]

aResponse-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


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.