Abstract CT193: Final results from a 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 , Tanabe Shunsuke , Kadota Tomoyuki , Ono Hiromi , Tsukamoto Kazuko , Ikeno Takashi , Wakabayashi Masashi , Sato Akihiro , Kondo Masanori , Kumagai Shogo , Koyama Shohei , Nishikawa Hiroyoshi , Doi Toshihiko 
Published: April 2023

Abstract
Background: PD-1 blockade showed promising efficacy for broad type of cancer patients (pts), though objective response rates are very limited. 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 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 (1 × 1010VP on cohort 1, 1 × 1011VP on cohort 2 and 1 × 1012VP 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 DLT. Secondary endpoints are 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. Biomarker study was planned to use paired samples of both tumor biopsy and blood. Clinical trial information: NCT03172819.
Results: A total 22 pts (phase Ia part: 11 pts, phase Ib part: 11 pts) were enrolled in the study from Dec 2017 to Feb 2021. Median age was 65. Among the pts, 18 had esophageal squamous cell carcinoma, 2 had gastric cancer, one EGJ cancer, and one had colon cancer. No DLT was observed and the recommended dose for phase Ib part was 1 × 1012VP (cohort 3). Eighteen pts was injected to primary site, and 5 pts injected to metastatic site (Lymph node:1, Liver:3). Common grade 3 or 4 adverse events were fever (4.5%), and abnormal hepatic function (4.5%). Objective tumour responses were documented in 2(9.1%) of 22 pts. Tumor samples were subjected to multiplex immunohistochemistry (17 pts) and showed that tumor-infiltrating PD-1+CD8+ T cells prior to the treatment were significantly higher in 5 responders who experienced PR or &gt;6 months SD, compared with 12 non-responders (P=0.0365).
Conclusion: The combination of OBP-301 with pembrolizumab was well tolerated and showed limited response. The result of biomarker analyses using paired samples of both tumor biopsy and blood will be presented. Tumor-infiltrating PD-1+CD8+ T cells could be a biomarker for this combinatory therapy.
Citation Format: Takashi Kojima, Toshiyoshi Fujiwara, Shunsuke Tanabe, Tomoyuki Kadota, Hiromi Ono, Kazuko Tsukamoto, Takashi Ikeno, Masashi Wakabayashi, Akihiro Sato, Masanori Kondo, Shogo Kumagai, Shohei Koyama, Hiroyoshi Nishikawa, Toshihiko Doi. Final results from a 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 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr CT193.