A phase I, open-label, dose-finding, safety, tolerability, and exploratory trial of intraperitoneal THEO-260 in patients with high-grade serous or endometrioid ovarian cancer.

Abstract

TPS5635 Background: Ovarian cancers are immunologically cold at baseline and typically characterized by a rich stromal component with a high proportion of cancer-associated fibroblasts (CAF). These features limit efficacy of immunotherapy and virotherapy due to the immunosuppressive effects of abundant CAFs. THEO-260 is an oncolytic adenovirus that exhibits selective replication, lysis, and killing of cancer cells and CAFs. This unique mechanism-of-action positions THEO-260 as a potential efficacious treatment option for patients with platinum-resistant ovarian cancer. Intraperitoneal (IP) delivery may further enhance efficacy by enabling high locoregional dose with lower systemic exposure. Methods: This phase I, open-label, single-institution study (NCT07211659) evaluates IP THEO-260 in patients with platinum-resistant or refractory high grade serous (HGS) or endometrioid ovarian, peritoneal, or fallopian tube cancer. The primary objectives are to evaluate the safety and tolerability of THEO-260 when administered intraperitoneally and to establish the recommended phase 2 dose (RP2D) using a Bayesian Optimal Interval design with 4 dose levels in cohorts of 3. Patients receive up to 6 doses of THEO-260 over 15 days: 2 desensitization doses followed by 4 target-dose administrations. Secondary objectives include PK, viral shedding, systemic cytokine release, and preliminary efficacy assessment. Response assessments will be conducted every 8 weeks starting on day 29 through week 52 and thereafter every 12 weeks until progression, death, or end of trial. Eligibility includes histologically confirmed, platinum-resistant or refractory HGS, endometrioid cancer of the ovary, peritoneum, or fallopian tube, measurable peritoneal disease per RECIST v1.1, ECOG 0-1, adequate organ function, life expectancy of ≥6 months, and feasibility of intraperitoneal catheter placement. Prior treatments must include optimal surgical debulking, bevacizumab, or PARP inhibitor therapy as indicated. Key exclusions include serosal disease >3cm, bowel obstruction history or symptoms, uncontrolled pleural or pericardial effusions, and prior pneumonitis or interstitial lung disease. Enrollment began in November 2025. Clinical trial information: NCT07211659 .