459P - Phase I study of ONO-4538 (BMS-936558), an anti PD-1 antibody, in Japanese patients with advanced solid tumors
|Date||01 October 2012|
|Event||ESMO Congress 2012|
|Session||Poster presentation III|
|Topics|| Drug Development
Cancer Immunology and Immunotherapy
N. Yamamoto1, Y. Yamada2, H. Nokihara1, H. Asahina3, T. Shibata1, Y. Tamura1, Y. Seki4, K. Honda1, Y. Tanabe5, T. Tamura1
ONO-4538 (BMS-936558) is a fully human monoclonal IgG4 antibody binding to Programmed cell death-1 (PD-1), a co-inhibitory receptor expressed on antigen-activated T cell. This phase I study was conducted to assess the tolerability, pharmacokinetics (PK), antitumor activity and immune response of ONO-4538 in Japanese patients (pts) with advanced solid tumors.Method
Pts with advanced solid tumors refractory to standard therapy, adequate organ functions and performance status of 0 or 1 were enrolled. Pts received ONO-4538 intravenously on day 1, day 22 & day 36 in the first 7 weeks, and then repeated every 2 weeks.Result
Seventeen pts (male/female: 10/7, PS 0/1: 4/13, non-small cell lung cancer (NSCLC): 5, melanoma: 4, colorectal cancer (CRC): 4, thymic cancer: 2, esophageal cancer: 1, thyroid cancer: 1), aged 34-74 (median: 61) years, were enrolled at a dose of 1 (n = 3), 3 (n = 5), 10 (n = 6) and 20 (n = 3) mg/kg. The major treatment-related AEs included lymphopenia (58.8%), eosinophilia (47.1%), pyrexia (29.4%), hypoalbuminemia (29.4%) and ventricular extrasystole (23.5%). Grade 3 lymphopenia was observed in 2 pts, which was resolved without any treatment. No dose-limiting toxicities were observed up to the dose of 20 mg/kg. The terminal half-life after a single dose of ONO-4538 was 13-21 days, and the AUC and Cmax increased proportionally within 1-20 mg/kg and 1-10 mg/kg, respectively. No clear change was observed in immunological parameters. Partial responses (PR) were achieved in 3 pts (CRC at 1 mg/kg, melanoma at 3 mg/kg and thyroid cancer at 10 mg/kg), and 2 of them (CRC and thyroid cancer) had response lasting 6 and 13 months, respectively. One melanoma pts was still on study with response duration of 28 months as of April 2012. Three pts (NSCLC at 3 mg/kg, thymic cancer and NSCLC at 10 mg/kg) had stable disease, and the former two pts continued the treatment > 6 months. Among 11 pts evaluable for IHC (immunohistochemistry) staining, 8 pts had high expression of PD-L1, a ligand of PD-1, on their tumor tissues, and 2 of them achieved PR. No pts with low PD-L1 expression showed objective response.Conclusion
ONO-4538 was well tolerated up to the 20 mg/kg and antitumor activity was observed within 1-10 mg/kg.Disclosure
N. Yamamoto: Chugai pharmaceutical co., ltd. Pfizer Kyowa-Hakko Kirin co., ltd.
Y. Yamada: Bayer Yakult AstraZeneca.
H. Nokihara: TAIHO PHARMACEUTICAL CO., LTD Merck Serono Pfizer.
T. Tamura: Chugai Pharmaceutical co., ltd. Daichi-Sankyo co., ltd. Boehringer Ingelheim ABBOTT JAPAN Co., LTD Eisai co., ltd. Bristol-Myers Squibb Kyowa-Hakko Kirin co., ltd.
All other authors have declared no conflicts of interest.