Abstract CT024: Early safety from an open label Phase I study to evaluate the safety and efficacy of a telomerase-specific oncolytic adenovirus (OBP-301) with pembrolizumab in patients with advanced solid tumors. (EPOC1505)
Authors: Kojima Takashi , Fujiwara Toshiyoshi , Shirakawa Yasuhiro , Hori Keisuke , Ono Hiromi , Nakamoto Masako , Hirano Nami , Wakabayashi Masashi , Nomura Shogo , Togashi Yosuke , Nishikawa Hiroyoshi , Sato Akihiro , Ohtsu Atushi , Doi Toshihiko 
Published: August 2019

Abstract
Background: PD-1 blockade showed promising efficacy for broad type of cancer patients (pts), though objective response rates are very limited. The antitumor potential of oncolytic adenoviruses has been demonstrated in preclinical and clinical studies. In addition to the specific killing of cancer cells via oncolytic adenovirus, these agents prompt the immune system to stimulate an antitumor immune response. OBP-301 is an oncolytic adenovirus in which gene is modified to be able to selectively replicate in cancer cells by introducing human telomerase reverse transcriptase (hTERT) promotor. Further antitumor effect might be expected with an active activation of two different antitumor immunity by OBP-301 in combination with pembrolizumab. Therefore, we conducted phase I study to evaluate the safety and efficacy of OBP-301 with pembrolizumab.
Methods: The major eligibility criteria are pts with advanced or metastatic solid tumor not responded to or intolerant of standard chemotherapies, and with possibility of intratumoral injection. Phase Ia part was designed to determine the recommended dose in a “3+3” cohort-based dose escalation design of OBP-301 (1x1010VP on cohort 1, 1x1011VP on cohort 2 and 1x1012VP on cohort 3) with pembrolizumab (200mg/body q3w). OBP-301 is administered at day1, 15, and, 29 by intratumoral injection and pembrolizumab is administered at day 8 and thereafter every 3 weeks. Primary endpoint is dose limiting toxicity (DLT). Secondary endpoint is response rate, progression free survival, and incidence of adverse event. Phase Ib part was designated to evaluate the safety and efficacy of the recommended dose OBP-301 selected in phase Ia part in combination with pembrolizumab in 10 pts. Biomarker study was planned using paired samples of both tumor biopsy and blood. Clinical trial information: NCT03172819.
Results: The first patient was enrolled on 7 Dec 2017; the last patient in phase Ia part was enrolled on 12 Oct 2018. Nine DLT-evaluable pts were enrolled and treated in phase Ia part: median age was 59; 2/9 female; 8/9 esophageal squamous cell carcinoma, 1/9 gastric adenocarcinoma. No DLT was observed during the DLT evaluation period. The most common adverse events were fever (Gr.2: 2/9, Gr.1: 2/9), hepatic disorder (Gr.3: 1/9, Gr.1: 1/9), pleural effusion (Gr.1:1/9). Preliminary efficacy assessment of phase Ia by investigators’ judgment demonstrated 2 PRs of the 9 pts.
Conclusion: The combination of OBP-301 with pembrolizumab was well tolerated in tested doses. The recommended dose for phase Ib part is 1x1012VP (cohort 3), and additional 10 pts will be enrolled to obtain additional safety and efficacy data. Preliminary result of biomarker analyses using paired samples of both tumor biopsy and blood will be presented.
Citation Format: Takashi Kojima, Toshiyoshi Fujiwara, Yasuhiro Shirakawa, Keisuke Hori, Hiromi Ono, Masako Nakamoto, Nami Hirano, Masashi Wakabayashi, Shogo Nomura, Yosuke Togashi, Hiroyoshi Nishikawa, Akihiro Sato, Atushi Ohtsu, Toshihiko Doi. Early safety from an open label Phase I study to evaluate the safety and efficacy of a telomerase-specific oncolytic adenovirus (OBP-301) with pembrolizumab in patients with advanced solid tumors. (EPOC1505) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr CT024.