Abstract A022: Phase 1/2 study to evaluate systemic durvalumab (durva) + intraperitoneal ONCOS-102 in patients with peritoneal disease who have epithelial ovarian (OC) or metastatic colorectal cancer (CRC)
Authors: Zamarin Dmitriy , Odunsi Kunle , Slomovitz Brian , Hubbard-Lucey Vanessa M. , McCabe Danielle , Shohara Lisa , Schwarzenberger Paul , Ricciardi Toni , Macri Mary , Ryan Aileen , Aksnes Anne-Kirsti , Kuryk Lukasz , Venhaus Ralph 
Published: February 2019

Abstract
Metastasis to the peritoneal cavity is associated with end-stage disease in many cancers, including epithelial ovarian cancer (OC) and colorectal cancer (CRC), both of which exhibit poor responses to checkpoint inhibitors. Oncolytic viruses may promote tumor recognition by the immune system. Evidence suggests that locoregional treatment with oncolytic viruses can be used to improve the efficacy of checkpoint inhibitors at both treated and distant tumor sites. ONCOS-102 is an oncolytic adenovirus encoding for granulocyte-macrophage colony stimulating factor (GMCSF). Durvalumab (durva), a checkpoint inhibitor, is a human IgG1 monoclonal antibody against programmed cell death ligand-1 (PD L1). This study evaluates the combination of intraperitoneally administered ONCOS-102 with systemic durva in patients with peritoneal disease who have histologically confirmed OC or metastatic CRC and have failed prior standard therapies.This ongoing phase 1/2, open-label study (NCT02963831) evaluates the safety and antitumor/biologic activity of durva (1500 mg intravenous, every 4 weeks x 12) + ONCOS-102 (intraperitoneal, weekly x 6); cyclophosphamide is given before the first ONCOS-102 dose. Phase 1 will follow a 3+3 design to evaluate the ONCOS 102 dose to be given with durva. Phase 2 will evaluate the activity of the combination using Simon’s 2-stage MINIMAX design. In Stage 1, the OC and CRC cohorts will enroll 18 and 13 patients, respectively. If ≥ 5 patients in the OC cohort or ≥ 1 patient in the CRC cohort are progression free at the end of Week 24 (PFS24W), then Stage 2 will enroll 15 and 14 additional patients in the OC and CRC cohorts for a total n of 33 and 27, respectively. The null/alternative hypotheses for PFS24W are 20/40% for OC and 5/20% for CRC. The null hypothesis will be rejected if ≥ 11 patients in the OC cohort or ≥ 4 patients in the CRC cohort experience PFS24W. The primary endpoints are safety/tolerability per Common Terminology Criteria for Adverse Events (CTCAE) for phase 1 and PFS24W rate by RECIST 1.1 for phase 2. Secondary endpoints are safety and tolerability, response rate at 8 and 24 weeks, progression-free survival, and overall survival. Exploratory endpoints are immunologic effects in tumors and peripheral blood. Enrollment opened 07 September 2017. As of 27 June 2018, 4 patients are enrolled; enrollment is ongoing.
Citation Format: Dmitriy Zamarin, Kunle Odunsi, Brian Slomovitz, Vanessa M. Hubbard-Lucey, Danielle McCabe, Lisa Shohara, Paul Schwarzenberger, Toni Ricciardi, Mary Macri, Aileen Ryan, Anne-Kirsti Aksnes, Lukasz Kuryk, Ralph Venhaus. Phase 1/2 study to evaluate systemic durvalumab (durva) + intraperitoneal ONCOS-102 in patients with peritoneal disease who have epithelial ovarian (OC) or metastatic colorectal cancer (CRC) [abstract]. In: Proceedings of the Fourth CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; Sept 30-Oct 3, 2018; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2019;7(2 Suppl):Abstract nr A022.