Discussion
tumor
DISEASE, MINOR, SOLID TUMORS, TUMOR
In this Phase Ib, open-label, dose-finding clinical study, we described the MTDs for different schedules, 125 mg (bid 5/9) and 300 mg (qd 5/2 and 5/9), and identified the RP2D of adavosertib monotherapy to be 300 mg (qd 5/2). Steady-state concentration at 300 mg (qd 5/2) was above the ICA previous Phase I dose-escalation study with once-daily adavosertib monotherapy in patients with advanced solid tumors identified the RP2D to be 300 mg qd 5/2 for 2 of 3 weeks [With the mandatory use of antiemetic prophylaxis, we demonstrated a safety profile broadly consistent with earlier monotherapy studies [Adavosertib monotherapy given in a range of exploratory doses showed minor antitumor activity in this heavily pre-treated group of patients with diverse tumor types. Stable disease for at least 8 weeks for qd 5/2 schedules, or at least 7 weeks for other schedules was observed in 28 (45.2%) patients and in 21 (33.9%) patients for more than 12 weeks; long-term clinical studies should build upon these findings. Evidence of efficacy with adavosertib monotherapy has also been shown in other studies. A Phase II study of adavosertib (300 mg qd on days 1–5 and 8–12 of a 21-day cycle) monotherapy in women with recurrent USC reported an ORR of 29.4% (95% CI 15.1–47.5) with a median PFS of 6.1 months [There was no apparent pharmacokinetic impact of administering adavosertib with a high-fat meal in this assessment. This was confirmed by and is in accordance with findings by Någård et al. [In conclusion, the RP2D of adavosertib monotherapy was 300 mg (qd 5/2 for 2 of 3 weeks). The safety profile was manageable and consistent with the known safety profile, with limited antitumor activity.