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 Clinical research
Basic Scientific Principles
Presenter Noboru Yamamoto
Authors N. Yamamoto1, Y. Yamada2, H. Nokihara1, H. Asahina3, T. Shibata1, Y. Tamura1, Y. Seki4, K. Honda1, Y. Tanabe5, T. Tamura1
  • 1Division Of Thoracic Oncology, National Cancer Center Hospital, 1040045 - Tokyo/JP
  • 2Medical Oncology, National Cancer Center Hospital, 1040045 - Tokyo/JP
  • 3First Department Of Medicine, National Cancer Center Hospital, 1040045 - Tokyo/JP
  • 4Department Of Thoracic Oncology, Shien-lab, National Cancer Center Hospital, 1040045 - Tokyo/JP
  • 5Breast And Medical Oncology Division, National Cancer Center Hospital, 104-0045 - Tokyo/JP



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.


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.


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.


ONO-4538 was well tolerated up to the 20 mg/kg and antitumor activity was observed within 1-10 mg/kg.


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.