Azenosertib plus paclitaxel for platinum-resistant ovarian cancer: Results from a phase 1b study.

Abstract

5529 Background: Most patients (pts) with ovarian cancer develop platinum-resistant disease following surgery and platinum-based chemotherapy and have a poor prognosis. Paclitaxel (PAC) monotherapy is the most efficacious chemotherapy for platinum-resistant ovarian cancer (PROC) but clinical benefits require further improvement. Azenosertib (Azeno) is a potentially best-in-class, novel, selective and orally bioavailable small molecule inhibitor of the WEE1 tyrosine kinase. Herein we report results from a Phase 1b study of Azeno plus PAC for PROC. Methods: MUIR (NCT04516447) is an open-label Phase 1b study evaluating the safety, efficacy and preliminary clinical activity of Azeno plus chemotherapy (Part 1 dose escalation) for PROC. Eligible pts were aged ≥18 years, had ECOG PS score ≤2, histologically/cytologically confirmed high-grade serous epithelial ovarian, fallopian tube, or peritoneal carcinoma, and measurable disease per RECIST v1.1; pts had received 1‒4 prior lines of systemic therapy and had platinum-resistant disease. Pts were assigned to 1 of 4 cohorts: carboplatin, gemcitabine, pegylated liposomal doxorubicin, or PAC (80 mg/m 2 IV on Days 1, 8 and 15 of 28-day cycles). Azeno plus PAC is the focus of this analysis where Azeno was orally administered 200 mg (continuously) or 200, 250 and 300 mg (intermittently 5 days on, 2 days off [5:2]) for 28-day cycles. Primary objectives were safety and tolerability. Clinical activity was a key secondary objective assessed by objective response rate (ORR) and duration of response (DOR) per RECIST v1.1, and progression-free survival. Exploratory objectives included analysis of baseline tumor and plasma biomarkers with optional biopsies/blood plasma. Results: As of December 1, 2025, 46 pts received Azeno (continuously 200 mg, n=7 and intermittently 5:2: 200 mg, n=15; 250 mg, n=12; 300 mg, n=12) plus PAC. Median age was 66 years (range 45‒83), median number of prior lines of therapy was 2 (range, 1‒4), and all pts received prior PAC. Most common treatment related adverse events (TRAEs) were fatigue (61%), anemia (59%), nausea (52%), and neutropenia (50%); most frequent grade ≥3 TRAEs were neutropenia (30%) and anemia (20%). Serious TRAEs occurred in 20% of pts. Overall, confirmed ORR was 39.1% (95% CI, 25.1‒54.6) with a median DOR of 5.6 months (95% CI, 5.6‒9.2) (Table). Conclusions: Azeno plus PAC showed promising clinical activity and tolerability in pts with PROC. ORR and median DOR were improved when compared historically with PAC monotherapy supporting the continued evaluation of this regimen in PROC and other indications. Clinical trial information: NCT04516447 . OR and median DOR. Azeno 5:2 Azeno 5:2 Azeno 5:2 Azeno 200 mg + PAC (n=7) 200 mg + PAC (n=15) 250 mg + PAC (n=12) 300 mg + PAC (n=12) All(N=46) ORR, %(95% CI) 57.1(18.4‒90.1) 20.0(4.3‒48.1) 50.0 (21.1‒78.9) 41.7 (15.2‒72.3) 39.1 (25.1‒54.6) Median DOR, months(95% CI) 7.8(5.6‒NE) 5.6(3.7‒NE) 9.2 (3.8‒NE) 5.6 (5.2‒NE) 5.6(5.6‒9.2) NE, not evaluable.