A randomized, multicenter, open-label, phase 2 basket study of CYP11A1 inhibitor opevesostat in participants with selected solid tumors: Study design of cohorts B and C of OMAHA-015

Abstract

Objectives: Opevesostat (MK-5684; ODM-208) is an oral, nonsteroidal selective inhibitor of CYP11A1, which catalyzes the first and rate-limiting step of steroid biosynthesis. By blocking the synthesis of all steroid hormones and their precursors, opevesostat has the potential to suppress steroid-driven tumor growth in ovarian or endometrial cancers. The randomized, open-label, phase 2 OMAHA-015 study (NCT06979596) is designed to evaluate the efficacy and safety of opevesostat in selected solid tumors. Method(s): Cohort B will enroll eligible participants with platinum-sensitive, histologically confirmed high-grade epithelial ovarian, fallopian tube, or primary peritoneal carcinoma, including high-grade serous or predominantly serous, high-grade endometrioid, clear cell, or malignant mixed Mullerian tumors (carcinosarcoma). Eligible participants must have received 4-8 cycles of platinum-based doublet chemotherapy in a third-line setting for ovarian cancer with <=9 weeks between the last dose of third-line chemotherapy and randomization. Cohort C will enroll eligible participants with histologically confirmed primary advanced/recurrent low-grade endometrioid carcinoma (FIGO grade 1/2, or well/moderately differentiated), with known pMMR status, and wild type p53 expression. Participants must either be treatment-naive or have received <=1 prior line of platinum-based therapy in the advanced/metastatic or adjuvant/neoadjuvant setting. In cohort B, approximately 90 participants will be randomly assigned 1:1 to either arm 3: oral opevesostat 5 mg twice daily (BID) plus daily corticosteroids; or arm 4: observation. In cohort C, approximately 80 participants will be randomly assigned 1:1 to either arm 5: oral opevesostat 5 mg BID plus daily corticosteroids; or arm 6: physician's choice of oral megestrol acetate 80 mg BID, alternating megestrol plus tamoxifen 20 mg BID, or oral letrozole 2.5 mg daily. The primary end point is progression-free survival per RECIST v1.1, assessed by blinded independent central review (BICR). Secondary end points include overall survival, objective response rate and duration of response per RECIST v1.1 assessed by BICR, as well as safety. OMAHA-015 is currently enrolling participants. Copyright © 2026