Study to evaluate intraperitoneal (IP) ONCOS-102 with systemic durvalumab in patients with peritoneal disease who have epithelial ovarian (OC) or metastatic colorectal cancer (CRC): Phase 2 results.

2600 Background: Locoregional treatment with oncolytic viruses may be used to improve the efficacy of immune checkpoint inhibitors at both treated and distant tumor sites. This study evaluated the combination of IP-administered ONCOS-102, an oncolytic adenovirus encoding for granulocyte macrophage colony stimulating factor (GM-CSF), with systemic durvalumab (durva) in patients (pts) with advanced OC or CRC who have failed prior chemotherapy. Methods: This open-label study (NCT02963831) evaluated ONCOS-102 (IP 3 x 1011 VP in 500ml saline [recommended phase 2 dose] weekly x 6) + durva (IV 1500 mg every 4 weeks x 12). One dose of cyclophosphamide was given prior to first ONCOS-102 dose. Phase 2 evaluated the activity of the combination using Simon’s 2-stage MINIMAX design. In MINIMAX stage 1, if ≥ 5 of 18 OC pts or ≥ 1 of 13 CRC pts met the efficacy criteria (progression free at end of week 24), 15 additional OC pts or 14 additional CRC pts were to be enrolled in stage 2. The efficacy endpoint would be met if ≥ 11 OC pts or ≥ 4 CRC pts remained progression free at 24 weeks. Safety, response rate and progression-free survival (PFS) by RECIST 1.1, overall survival (OS), and immunologic effects in tumors were evaluated. ITT population = all pts who received at least one dose of durva or ONCOS-102; per protocol (PP) population = all pts who received at least 60% of ONCOS-102 doses and at least 1 durva dose in the first 2 cycles. Results: In MINIMAX stage 1, the OC cohort did not meet the efficacy criteria and was closed. For CRC, stage 1 efficacy criteria were achieved and the cohort was opened for stage 2. As of the 14 Dec 2021 cutoff, CRC enrollment was complete, and all pts were followed for 24 weeks or until progression or off study. Two pts were progression free at 24 weeks (see table). Treatment-related adverse events (TRAEs) occurring in > 30% pts were vomiting, nausea, fatigue, chills, and pyrexia. There were no grade 4 or 5 TRAEs. Grade 3 TRAEs were reported in 8 pts, 2 in the OC cohort and 6 in CRC. All grade 3 TRAEs occurred in no more than 1 pt for each AE except abdominal pain, which occurred in 2 pts. Conclusions: The combination of IP ONCOS-102 and durva was well tolerated. The study did not meet its efficacy endpoint. Evaluation of pre- and on-therapy translational parameters is ongoing. Clinical trial information: NCT02963831. [Table: see text]