Adavosertib with chemotherapy (CT) in patients (pts) with platinum-resistant ovarian cancer (PPROC): An open label, four-arm, phase II study.

Abstract

5513 Background: Adavosertib (AZD1775; A), a highly selective WEE1 inhibitor, demonstrated activity and tolerability in combination with carboplatin (C) in primary PROC. This study (NCT02272790) assessed the objective response rate (ORR) and safety of A in PROC. Methods: Pts with recurrent RECIST v1.1 measurable PROC received A with C, gemcitabine (G), weekly paclitaxel (P), or pegylated liposomal doxorubicin (PLD) in 3- (C) or 4-week (G, P, PLD) cycles (Table). Tumor assessments were performed every 2 cycles until disease progression. Primary objective: ORR; other objectives: disease control rate (DCR), progression-free survival (PFS) and safety. Results: In the 94 pts treated (median treatment duration 3 months; range 0–16 months), outcomes were greatest with A (weeks [W]1–3) + C (Table), with ORR of 67% and median PFS (mPFS) of 10.1 months for this cohort. Most common grade ≥3 treatment-emergent adverse events (TEAEs) are shown in the Table, with hematologic toxicity most notable with A (W1–3) + C. TEAEs led to A dose interruptions, reductions and discontinuations in 63%, 30% and 13% of the whole cohort, respectively. A possible positive relationship between CCNE1 amplification and response warrants further investigation. Conclusions: A shows preliminary efficacy when combined with CT. Pts receiving A (W1–3) + C showed greatest benefit. The increased but not unexpected hematologic toxicity is a challenge and could be further studied to optimize the dose schedule and supportive medications. Clinical trial information: NCT02272790. [Table: see text]