At the ESMO Congress 2026, Fiona Simpkins (Philadelphia, United States) presented interim overall survival findings from Part 1b of the phase II DENALI study (GOG-3066; NCT05128825), evaluating azenosertib in patients with platinum-resistant ovarian cancer.
The investigational oral WEE1 inhibitor demonstrated a median overall survival (OS) of 15.8 months in patients with Cyclin E1-positive tumors, compared with 7.5 months in those with Cyclin E1-negative disease, suggesting a potential role for Cyclin E1 expression in identifying patients more likely to benefit from treatment.
Methods
DENALI is a multi-part, open-label phase II study evaluating the safety and efficacy of azenosertib, a selective WEE1 tyrosine kinase inhibitor, in patients with platinum-resistant high-grade serous ovarian, fallopian tube, or primary peritoneal cancer.
Eligible patients had measurable disease according to RECIST v1.1, an ECOG performance status of 0–1, and had received 1–5 prior lines of systemic therapy, including bevacizumab.
Patients received oral azenosertib at 400 mg once daily on a five-days-on, two-days-off schedule until disease progression or unacceptable toxicity.
Cyclin E1 expression was assessed retrospectively using immunohistochemistry (IHC) and a proprietary cutoff. The primary endpoint was objective response rate, while secondary endpoints included duration of response, progression-free survival, overall survival, and safety.
Key Takeaways
At the September 2, 2025, data cutoff, 102 patients were included in the full analysis set, of whom 94 were evaluable for Cyclin E1 expression.
- Cyclin E1-positive subgroup: Median OS was 15.8 months (95% CI, 8.7–17.8; n=48).
- Cyclin E1-negative subgroup: Median OS was 7.5 months (95% CI, 5.8–12.3; n=46).
- Overall population: Median OS was 12.3 months (95% CI, 8.7–16.1; n=102).
- Previously reported efficacy: Azenosertib demonstrated an approximately 35% objective response rate in response-evaluable patients with Cyclin E1-positive tumors, with a median duration of response of 6.3 months.
- Safety: No new safety signals were identified in the interim analysis.
The observed survival difference suggests that Cyclin E1 expression may be associated with improved outcomes following azenosertib treatment. However, the nonrandomized study design and retrospective biomarker assessment do not establish Cyclin E1 as a predictive biomarker.
Conclusion
The interim DENALI Part 1b findings demonstrated encouraging survival outcomes with azenosertib in patients with Cyclin E1-positive platinum-resistant ovarian cancer.
The 15.8-month median overall survival in the biomarker-positive subgroup supports continued investigation of WEE1 inhibition in this population. However, the single-arm design and retrospective biomarker assessment limit conclusions about comparative survival benefit.
Further evaluation is ongoing in DENALI Part 2 and the phase III ASPENOVA confirmatory study, which aim to clarify the clinical benefit of azenosertib in patients with Cyclin E1-positive platinum-resistant ovarian cancer.
Source: ESMO Congress 2026 abstract; DENALI study (GOG-3066; NCT05128825).
