Multicenter Phase II Trial of the WEE1 Inhibitor Adavosertib in Refractory Solid Tumors Harboring

Authors

Siqing Fu
Shuyang Yao
Yuan Yuan
Rebecca A Previs
Anthony D Elias
Richard D Carvajal
Thomas J George
Ying Yuan
Lihou Yu
Shannon N Westin
Yan Xing
Ecaterina E Dumbrava
Daniel D Karp
Sarina A Piha-Paul
Apostolia M Tsimberidou
Jordi Rodon Ahnert
Naoko Takebe
Karen Lu
Khandan Keyomarsi
Funda Meric-Bernstam

Publication Date

3-20-2023

Journal

Journal of Clinical Oncology

Abstract

PURPOSE: Preclinical cancer models harboring

PATIENTS AND METHODS: Patients aged ≥ 18 years with measurable disease and refractory solid tumors harboring

RESULTS: Thirty patients were enrolled. The median follow-up duration was 9.9 months. Eight patients had partial responses (PRs), and three had stable disease (SD) ≥ 6 months, with an ORR of 27% (95% CI, 12 to 46), a SD ≥ 6 months/PR rate of 37% (95% CI, 20 to 56), a median progression-free survival duration of 4.1 months (95% CI, 1.8 to 6.4), and a median overall survival duration of 9.9 months (95% CI, 4.8 to 15). Fourteen patients with epithelial ovarian cancer showed an ORR of 36% (95% CI, 13 to 65) and SD ≥ 6 months/PR of 57% (95% CI, 29 to 82), a median progression-free survival duration of 6.3 months (95% CI, 2.4 to 10.2), and a median overall survival duration of 14.9 months (95% CI, 8.9 to 20.9). Common treatment-related toxicities were GI, hematologic toxicities, and fatigue.

CONCLUSION: Adavosertib monotherapy demonstrates a manageable toxicity profile and promising clinical activity in refractory solid tumors harboring

Keywords

Female, Humans, Carcinoma, Ovarian Epithelial, Bayes Theorem, Antineoplastic Agents, Ovarian Neoplasms, Oncogene Proteins, Cyclin E, Protein-Tyrosine Kinases, Cell Cycle Proteins

Comments

Trial registration: ClinicalTrials.gov NCT03253679.

DOI

10.1200/JCO.22.00830

PMID

36469840

PMCID

PMC10489509

PubMedCentral® Posted Date

December 2022

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes