Phase Ib/II clinical trial of oncolytic virus intravesical irrigation for preventing recurrence after TURBT in patients with recurrent high-risk NMIBC.

763 Background: Oncolytic virus therapy represents a novel approach in cancer treatment, showing promising results in non-muscle-invasive bladder cancer (NMIBC). OH2 injection is a recombinant oncolytic virus, derived from genetically modified HSV-2 strain HG52, which is confirmed efficacy in certain malignant tumors. This clinical trial aims to evaluate the safety and preliminary efficacy of using OH2 injection solution for intravesical irrigation to prevent recurrence in patients with high-risk NMIBC who have failed first-line preventive irrigation therapy. Methods: This study included pathology confirmed high-risk NMIBC patients who had undergone TURBT after failing first-line preventive bladder irrigation therapy and had been confirmed to be free of tumor residue. To be eligible for enrollment, patients needed to have adequate organ function, an ECOG performance status of 2 or less, and be ineligible for or refused radical cystectomy. Those with muscle invasive or locally advanced metastatic bladder cancer were excluded. Following enrollment, patients received OH2 with normal saline intravesical irrigation. The irrigation was given every two weeks for 5 times, followed the sixth irrigation after 3 weeks, then once a month till a year. We evaluated the 6-month and 12-month recurrence-free survival (RFS) rates and safety following the administration of oncolytic virus irrigation during the induction and maintenance treatment. Results: Thirty patients were planned to enroll in this clinical trial. The data of 9 high risk NMIBC patients could be analyzed at this time. Most of the patients (6 out of 9) received BCG treatment before. The 6-month RFS rate was 66.7%, the 12-month RFS rate was 55.6%, and the median RFS was 353 days. One patient who failed after the BCG treatment had the long RFS nearly 2 years. In terms of safety, adverse effects observed were consistent with the known safety profile of the agent. The most common complain included transient genitourinary symptoms which might be due to TURBT. The symptoms did not worsen during the treatment process. No significant adverse effects related to OH2 irrigation was observed. Conclusions: OH2 injection is independently developed domestically and is the first in China to be used for intravesical irrigation therapy for recurrent high-risk NMIBC, particularly in patients who have failed BCG therapy. According to our data, OH2 injection intravesical irrigation is safe. The long term efficacy deserves further research. Clinical trial information: NCT05232136 .