The following is a summary of “Multicenter Phase II Trial of the WEE1 Inhibitor Adavosertib in Refractory Solid Tumors Harboring CCNE1 Amplification,” published in the March 2023 issue of Oncology by Fu, et al.

For a phase II study, researchers sought to assess the antitumor activity of adavosertib, a WEE1 kinase inhibitor, in patients aged ≥18 with measurable disease and refractory solid tumors harboring CCNE1 amplification, an Eastern Cooperative Oncology Group performance status of 0-1, and adequate organ function. Preclinical cancer models had demonstrated that tumors with CCNE1 amplification were more sensitive to adavosertib treatment than those without amplification.

The trial enrolled 30 patients who received 300 mg of adavosertib once daily on days 1 through 5 and 8 through 12 of a 21-day cycle. The study followed a Bayesian optimal phase II design, with the primary endpoint being the objective response rate (ORR).

Results showed that 8 patients had partial responses (PRs), and three had stable disease (SD) ≥ 6 months, with an ORR of 27% (95% CI, 12 to 46), an 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). Among 14 patients with epithelial ovarian cancer, the ORR was 36% (95% CI, 13 to 65), the SD≥ 6 months/PR rate was 57% (95% CI, 29 to 82), the median progression-free survival duration was 6.3 months (95% CI, 2.4 to 10.2), and the median overall survival duration was 14.9 months (95% CI, 8.9 to 20.9).

Common treatment-related toxicities were gastrointestinal (GI) toxicities, hematologic toxicities, and fatigue.

In conclusion, adavosertib monotherapy demonstrated a manageable toxicity profile and promising clinical activity in treating refractory solid tumors harboring CCNE1 amplification, particularly in epithelial ovarian cancer. Therefore, further research on adavosertib, alone or in combination with other therapeutic agents, in CCNE1-amplified epithelial ovarian cancer was recommended.

Reference: ascopubs.org/doi/full/10.1200/JCO.22.00830