OATH trial: A phase II clinical trial evaluating the combination of onapristone with anastrozole for women with hormone receptor positive endometrial cancer—Preliminary results.

person Russell J. Schilder Thomas Jefferson University Hospital, Philadelphia, PA info_outline Russell J. Schilder, Mark S. Shahin, Mitchell Edelson, Norman G. Rosenblum, Ashley Douglas, Saveri Bhattacharya, Tarek Sahmoud, Elizabeth Burton, Avnish K Bhatia

Authors person Russell J. Schilder Thomas Jefferson University Hospital, Philadelphia, PA info_outline Russell J. Schilder, Mark S. Shahin, Mitchell Edelson, Norman G. Rosenblum, Ashley Douglas, Saveri Bhattacharya, Tarek Sahmoud, Elizabeth Burton, Avnish K Bhatia Organizations Thomas Jefferson University Hospital, Philadelphia, PA, Abington Hospital-Jefferson Health, Abington, PA, Gyn Onc Inst, Blue Bell, PA, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, PA, Thomas Jefferson University, Philadelphia, PA, University of Pennsylvania Health System, Philadelphia, PA, Context Therapeutics, Philadlephia, PA, Sidney Kimmel Cancer Center, Philadelphia, PA Abstract Disclosures Research Funding Institutional Funding Thomas Jefferson University, Context Therapeutics Background: Endometrial cancer is the most common gynecologic cancer and is primarily treated with chemotherapy. Many endometrial cancers though express hormone receptors and may respond to hormonal therapy, a potentially attractive non-chemotherapy alternative in such a population of women. The aim of OATH is to investigate the potential of dual hormonal blockade through the combination of antiprogesterone and anti-estrogen therapy via the administration of onapristone extended release (ONA) plus anastrozole (ANA), respectively. OATH is an open-label, multicenter, investigator-initiated, non-randomized, phase 2 study to evaluate the safety and efficacy of ONA + ANA in patients (pts) with endometrial cancer (EC). ClinicalTrials.gov Identifier: NCT04719273. Methods: Pts received ONA 50 mg twice daily plus ANA 1 mg once daily and were treated until progressive disease (PD) or unacceptable toxicity. Co-primary endpoints were 4-month progression-free survival (PFS) rate and overall response rate (ORR). A sample size of 25 pts will achieve 80% power to detect an improvement in 4-month PFS estimates from 25% (historical) to 52% and an improvement in response rate from 15% (historical) to 37%, using two-sided exact test at 5% significance level. Secondary endpoints include PFS, disease control rate (DCR), and safety. Results: As of January 20, 2023, 14 pts were enrolled. Median age was 67 years (44-80). ECOG performance status was 0 (36%), and 1 (64%). Number of prior chemotherapy regimens was 0 (1 pt,7%), 1 (9 pts, 64%) and 2 (4 pts, 29%). Seven (50%) pts received radiotherapy and 3 (21%) pts received prior checkpoint inhibitor therapy. Median treatment duration was 4.2 (1.0-19.9) months, and 8 pts remain on treatment. Adverse events were mainly grade 1 and 2. The most common treatment-related adverse events (AEs) and abnormal laboratory values were hot flashes (36%), alanine transferase (ALT) increased (29%), aspartate aminotransferase (AST) increased (29%), nausea (29%), and diarrhea (21%). No treatment-related serious AE, deaths on treatment, or treatment-related drug discontinuations were reported. The 4-month PFS Kaplan-Meier rate was 63.5%. Among 13 pts who had at least one tumor assessment after baseline, the best overall response was: 1 complete response, 1 partial response (response rate: 15.4%), 9 (69%) stable disease, and 2 (15.4%) progressions. Updated results will be presented. Conclusions: Preliminary results of dual hormonal blockade using ONA and ANA in heavily pretreated pts with EC suggest that this combination ONA + ANA has promising activity and is well tolerated. Clinical trial information: NCT04719273.

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