ADAGIO: a phase IIb international study of the Wee1 inhibitor adavosertib in women with recurrent or persistent uterine serous carcinoma

BACKGROUND: Uterine serous carcinoma is a distinct histologic subtype of endometrial cancer with an aggressive phenotype, poor prognosis, and limited therapeutic options. A previous proof-of-concept phase II trial of the Wee1 inhibitor adavosertib in uterine serous carcinoma demonstrated evidence of durable clinical activity. PRIMARY OBJECTIVE: To evaluate the efficacy of adavosertib in women with recurrent or persistent uterine serous carcinoma. STUDY HYPOTHESIS: We hypothesize that adavosertib will demonstrate significant clinical activity, as measured by objective response rate, in women with recurrent or persistent uterine serous carcinoma. TRIAL DESIGN: Eligible participants will receive adavosertib monotherapy until disease progression or unacceptable toxicity, starting at the recommended phase II dosing of adavosertib 300 mg daily days 1 through 5 and 8 through 12 of a 21-day cycle. Participants will have restaging studies every 6 weeks for the first 48 weeks and then every 9 weeks thereafter. MAJOR INCLUSION/EXCLUSION CRITERIA: Patients with histologically confirmed recurrent or persistent uterine serous carcinoma, including endometrial carcinoma of mixed histology where the serous component comprises at least 10% of the tumor, and who have received at least one prior platinum-based chemotherapy regimen for the management of uterine serous carcinoma, are eligible for inclusion in the trial. Participants must have measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. Participants with carcinosarcoma are not eligible. PRIMARY ENDPOINT: The primary endpoint is the objective response rate by RECIST 1.1 criteria, as determined by blinded independent central review. SAMPLE SIZE: Approximately 120 patients will be enrolled in this trial. ESTIMATED DATES FOR COMPLETING AND PRESENTING RESULTS: Study completion and presentation of results are projected to be at the end of 2022. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04590248.