Abstract CT166: TRX-E-002-1 in treatment-refractory ovarian cancer - 3-month follow-up results from a phase I study dose escalation phase
Authors: Coward Jermaine , Kichenadasse Ganessan , Harnett Paul , Moore Kathleen , Barve Minal , Berg Daniel , Garner James , Dizon Don 
Published: September 2020

Abstract
Introduction: The poor outcomes associated with current therapies for recurrent epithelial ovarian cancer (EOC) are thought to reflect the existence of drug-resistant ovarian cancer stem cells (OCSCs). The introduction of emerging therapies such as anti-angiogenic monoclonal antibodies and PARP inhibitors have added to the treatment armamentarium but have generated new resistance mechanisms to contend with. TRX-E-002-1 is a novel, 3rd generation benzopyran molecule that induces caspase-dependent and -independent apoptosis in CD44 +ve ovarian cancer stem-like cells and CD44 -ve ovarian somatic cancer cells. The dose escalation phase of a progressive design trial investigating intraperitoneal (IP)-administered TRX-E-002-1 monotherapy and in combination with standard of care for recurrent EOC (NCT02903771) has been completed with a Maximum Tolerated Dose (MTD) of 5 mg/kg established. Methods: Women with platinum-resistant relapsed disease, platinum refractory disease, or documented intolerance to platinum therapy were enrolled into the study. Patients had completed at least 2 or more prior regimens (including adjuvant therapy) prior to enrolment. Patients were dosed weekly with single agent TRX-E-002-1 IP for the first 2 cycles after which addition of pre-defined standard intravenous chemotherapy regimens was allowed cycles 3-8. Patients were followed up for 3 months after the end of treatment. Assessments included disease response, based on CA-125 and Response Evaluation Criteria in Solid Tumours or GCIG criteria along with circulating epithelial tumour cells (CETC) and stem cell markers. Results: For the 11 evaluable patients, on average, 4 prior lines of therapy, across a range of current and emerging treatments were completed. A total of 9 subjects were evaluable for MTD analysis with 5 patients showing stable disease on monotherapy per RECIST 1.1 criteria and 4 completing 8 cycles (6 months) of treatment; 2 remained progression-free at the 3-month endpoint post-treatment. Preliminary data on activity includes 2 partial responses (PR) per RECIST 1.1 criteria observed at follow-up. With no measurable disease per RECIST 1.1 criteria, 1 patient demonstrated a complete response (CR) during combination treatment which was maintained through-out follow-up, as per GCIG criteria in patients without initial measurable disease. Median progression free survival shown to be 5.5 months. CETC data for responders shows growth of circulating cancer stem cells no longer detected during cultivation of epithelial-antigen +ve cells indicating that the epithelial antigen cells present are not capable of clonal expansion. Conclusion: IP administered TRX-E-002-1 as a first-in-class, dual acting, anti-cancer therapy has preliminary activity for the treatment of platinum resistant ovarian cancer for patients who have demonstrated resistance to a range of prior treatments.
Citation Format: Jermaine Coward, Ganessan Kichenadasse, Paul Harnett, Kathleen Moore, Minal Barve, Daniel Berg, James Garner, Don Dizon. TRX-E-002-1 in treatment-refractory ovarian cancer - 3-month follow-up results from a phase I study dose escalation phase [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr CT166.