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.
- uterine cancer
Data availability statement
There are no data in this work.
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Contributors All authors participated in the writing, editing, and approval of this manuscript. JFL accepts full responsibility for the finished work and/or the conduct of the study, had access to the data, and controlled the decision to publish.
Funding This study was funded by AstraZeneca.
Competing interests JL is the international PI for the ADAGIO study and is also a member of the safety review committee for the study. JL has received consulting fees from AstraZeneca, Clovis, Eisai, EpsilaBio, Genentech, GlaxoSmithKline/Tesaro, and Regeneron Pharmaceuticals for advisory board participation; and trial support is provided to JL’s institution for trials on which JL is the PI by 2X Oncology, Aravive, Arch Oncology, AstraZeneca, Bristol-Myers Squibb, Clovis Oncology, CytomX Therapeutics, GlaxoSmithKline, Regeneron, Surface Oncology, Tesaro, and Vigeo Therapeutics. AMO is a member of the Safety Review Committee for the ADAGIO study. NC has received grant and contract support from AstraZeneca and Roche; consulting fees from Roche, PharmaMar, AstraZeneca, Clovis Oncology, MSD, GlaxoSmithKline, Tesaro, Pfizer, BIOCAD, Immunogen, Mersana, Eisai, and Oncxerna; payment or honoraria from AstraZeneca, Tesaro, Novartis, Clovis, MSD, GlaxoSmithKline, and Eisai; and has participated in a data safety monitoring board or advisory board for Roche, PharmaMar, AstraZeneca, Clovis Oncology, MSD, GlaxoSmithKline, Tesaro, Pfizer, BIOCAD, Immunogen, Mersana, Eisai, and Oncxerna. AO has received funding for her institution from Abbvie, Ability Pharmaceuticals, Advaxis Inc, Aeterna Zentaris, AMGEN, SA, Aprea Therapeutics, Clovis Oncology Inc, EISAI LTD, F. Hoffmann – La Roche LTD, Regeneron Pharmaceuticals, Immunogen Inc, Merck, Sharp & Dohme, Millennium Pharmaceutical Inc, Pharma Mar SA, BMS (Bristol Myers Squibb), and Tesaro; support for attending meetings and/or travel from Roche, AstraZeneca, and PharmaMar; and has participated on a data safety monitoring board or advisory board for AstraZeneca, Clovis Oncology Inc, Corcept Therapeutics, Deciphera Pharmaceutical, Eisai Europe Limited, EMD Serono Inc, F. Hoffmann-La Roche, GSK, Got It Consulting, SL, Immunogen, KL Logistics, Medison Pharma, Merck Sharp & Dohme, Mersana Therapeutics, Novocure GmbH, PharmaMar, PrIME Oncology, Roche Farma, Sutro Biopharma, Inc, and Tesaro.
Provenance and peer review Commissioned; internally peer reviewed.