1109O - Clinical activity and safety of anti-programmed death-1 (PD-1) (BMS-936558/MDX-1106/ONO-4538) in patients (pts) with advanced melanoma (MEL)

Date 29 September 2012
Event ESMO Congress 2012
Session Melanoma
Topics Pharmacology
Melanoma and other Skin Tumours
Presenter Jeff Sosman
Authors J. Sosman1, M. Sznol2, D.F. McDermott3, R. Carvajal4, D. Lawrence5, S.L. Topalian6, J.M. Wigginton7, G. Kollia8, A. Gupta9, F.S. Hodi10
  • 1Melanoma And Tumor Immunotherapy Program, Vanderbilt University Medical Center, Nashville/US
  • 2Section Of Medicine Oncology, Yale Cancer Center, New Haven/US
  • 3Biology Therapy Program, Beth Israel Deaconess Medical Center, Boston/US
  • 4Memorial Sloan-Kettering Cancer Center, New York/US
  • 5Massachusetts General Hospital Cancer Center, Boston/US
  • 6Melanoma Program, Sidney Kimmel Cancer Center at Johns Hopkins University, Baltimore/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
  • 10Melanoma Center, Dana-Farber Cancer Institute, Boston/US

Abstract

Purpose

BMS-936558 is a monoclonal antibody that blocks the PD-1 co-inhibitory receptor expressed by activated T cells. This study describes its activity and safety in pts with previously treated advanced MEL.

Methods

BMS-936558 was administered IV q2wk to pts with various tumors at 0.1 − 10 mg/kg during dose-escalation and/or cohort expansion. 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, 104 MEL pts had received BMS-936558 at 0.1 (n = 17), 0.3 (n = 19), 1 (n = 31), 3 (n = 17), or 10 mg/kg (n = 20). ECOG performance status was 0/1/2 in 63/38/3 pts, respectively. Most pts (67/104) had received prior immunotherapy (IT); prior anti-CTLA-4, -PD-1, or -PD-L1 was not permitted. The number of prior therapies was 1 (39%), 2 (35%), or ≥3 (26%). Median therapy duration was 20 wks (range 2.0 − 121.7 wks). The incidence of grade 3 − 4 related AEs was 20% and included gastrointestinal (4%), endocrine (2%), and hepatobiliary disorders (1%). There were no drug-related deaths in MEL pts. Clinical activity (responses or prolonged stable disease) was observed at all doses (Table). Of the 26/94 (28%) evaluable responders, 19 (73%) are ongoing ranging from 1.9+ to 24.9+ months. For the 23 responders followed ≥6 months from first dose on study, 16 (70%) are progression free. ORs occurred in pts with visceral or bone metastases. Six pts (6%; 95% CI 2 − 13%) had prolonged SD (≥24 wk); 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 durable clinical benefit in pts with advanced MEL, including those who had received prior IT. Additional long-term follow-up data will be reported.

Dose, (mg/kg) No. ptsa ORR,No. pts (%)[95% CI] PFSR at24 wk (%)[95% CI]
0.1 14 4 (29) [8 − 58] 40 [13 − 66]
0.3 16 3 (19) [4 − 46] 31 [9 − 54]
1 27 8 (30) [14 − 50] 45 [26 − 65]
3 17 7 (41) [18 − 67]* 55 [30 − 80]
10 20 4 (20) [6 − 44] 30 [9 − 51]

*1 CR aResponse-evaluable pts dosed by 7/01/2011 ORR = objective response rate ([{CR + PR} ÷ n] × 100); PFSR = progression-free survival rate.

Disclosure

J. Sosman: Research Funding: Bristol-Myers Squibb (myself).

M. Sznol: Consultant or Advisory Role: Bristol-Myers Squibb (myself, compensated). Research Funding: Bristol-Myers Squibb (myself, clinical trials funding).

D.F. McDermott: Advisory Board Role: Bristol-Myers Squibb (myself).

R. Carvajal: Research Funding: Bristol-Myers Squibb (myself).

S.L. Topalian: Consultant or Advisory Role: Bristol-Myers Squibb (myself, immediate family member, uncompensated). Research Funding: Bristol-Myers Squibb (myself).

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

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

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

F.S. Hodi: Consultant or Advisory Role: Bristol-Myers Squibb (myself, uncompensated). Research Funding: Bristol-Myers Squibb (myself).

All other authors have declared no conflicts of interest.