784O - Clinical activity and safety of anti-programmed death-1 (PD-1) (BMS-936558/MDX-1106/ONO-4538) in patients (pts) with previously treated, metastatic...

Date 01 October 2012
Event ESMO Congress 2012
Session Genitourinary tumors, renal cancer
Topics Anti-Cancer Agents & Biologic Therapy
Renal Cell Cancer
Presenter David McDermott
Authors D.F. McDermott1, C. Drake2, M. Sznol3, T. Choueiri4, J.D. Powderly5, D. Smith6, J.M. Wigginton7, G. Kollia8, A. Gupta9, M.B. Atkins10
  • 1Division Of Hematology/oncology, Beth Israel Deaconess Medical Center, Boston/US
  • 2Department Of Urology, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore/US
  • 3Section Of Medicine Oncology, Yale Cancer Center, New Haven/US
  • 4Lank Center For Genitourinary Oncology, Dana-Farber Cancer Institute/Brigham and Women's Hospital, Harvard Medical School, Boston/US
  • 5Oncology, Carolina Bio-Oncology Institute, Huntersville/US
  • 6Department Of Internal Medicine, University of Michigan, Ann Arbor/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
  • 10Internal Medicine, Georgetown Lombardi Comprehensive Cancer Center, Washington DC/US

Abstract

Purpose

BMS-936558 is a fully human monoclonal antibody that blocks the PD-1 co-inhibitory receptor expressed by activated T cells. In the initial portion of a phase 1 study, BMS-936558 showed promising activity in pts with various solid tumors, including mRCC. Accrual was expanded to better characterize antitumor, safety, and dose effects.

Methods

Pts with RCC were treated with BMS-936558 IV q2wk at 10 mg/kg initially, followed by additional pts at 1 mg/kg. Pts received up to 12 cycles (4 doses/cycle) of treatment or until unacceptable toxicity, confirmed progressive disease, or complete response (CR). Clinical activity was assessed by RECIST v1.0.

Results

As of Feb 24, 2012, 34 mRCC pts had been treated at 1 mg/kg (n = 18) or 10 mg/kg (n = 16). ECOG performance status was 0 in 13 pts and 1 in 21 pts. The number of prior therapies was 1 (n = 10), 2 (n = 9), or ≥3 (n = 15), and included prior immunotherapy (n = 20) or antiangiogenic therapy (n = 25); 32/34 pts had prior nephrectomy. Sites of metastatic disease included lymph node (n = 28), liver (n = 9), lung (n = 30), and bone (n = 10). Median duration of therapy was 32 wks (range 4 − 97.3 wks). The incidence of grade 3 − 4 related adverse events was 18% and included hypophosphatemia (6%), elevated ALT (3%), and cough (3%); there were no drug-related deaths among mRCC pts. Clinical activity (response or prolonged stable disease) was observed at both doses (Table). Two pts had a persistent reduction in target lesion tumor burden in the presence of new lesions and were not categorized as responders. There were responses in all sites of disease.

Conclusions

BMS-936558 is well tolerated and has durable clinical activity in pts with previously treated, mRCC. Additional long-term follow-up data will be reported.

Dose (mg/kg) No. ptsa ORRNo. pts (%)[95% CI] Response duration (months) SD ≥24 wk No. pts (%) [95% CI] PFSR at24 wk (%) [95% CI]
1 17 4 (24) [7 − 50] 17.5 + , 9.2 + , 9.2, 5.6+ 4 (24) [7 − 50] 47 [23 − 71]
10 16 5 (31) [11 − 59]* 22.3 + , 21.7 + , 12.9, 12.0, 8.4 5 (31) [11 − 59] 67 [43 − 91]

aResponse-evaluable pts dosed by 07/01/2011 *1 CR ORR = objective response rate ([{CR + PR} ÷ n] × 100); SD = stable disease; PFSR = progression-free survival rate.

Disclosure

D.F. McDermott: Advisory Role: Bristol-Myers Squibb (myself, Ad board participation).

C.G. Drake: Consultant or Advisory Role: Bristol-Myers Squibb, Dendreon Inc., and Amplimmune Inc. (myself, compensated). Stock Ownership: Amplimmune (myself). Other Renumerations: Patents Licensed, Bristol-Myers Squibb (myself).

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

T.K. Choueiri: Consultant or Advisory Role: GlaxoSmithKline, Aveo, Novartis and Pfizer (myself, compensated). Research Funding: Pfizer (myself).

J.D. Powderly: Consultant or Advisory Role: MedicineX and Bristol-Myers Squibb (myself, compensated). Research Funding: Bristol-Myers Squibb (clinical trials funding, myself). Honoraria: Bristol-Myers Squibb (ipilimumab speakers bureau, myself).

D.C. Smith: Research Funding: Bristol-Myers Squibb Oncology (myself).

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 (BMY) (myself).

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

M.B. Atkins: Advisory or Consultant Role: Bristol-Myers Squibb, Curetech, and Merck (myself, compensated).