At the ESMO Congress 2026, Domenica Lorusso (Pieve Emanuele, Italy) presented preliminary findings from an ongoing phase I study (NCT05238922), evaluating INCB123667, a selective oral cyclin-dependent kinase 2 (CDK2) inhibitor, in combination with bevacizumab in patients with recurrent epithelial ovarian cancer.
The investigational combination demonstrated promising antitumor activity, achieving an objective response rate (ORR) of 48% and a disease control rate (DCR) of 91% in heavily pretreated patients, including those previously exposed to bevacizumab and PARP inhibitors.
Methods
The ongoing phase I study evaluated the safety and preliminary efficacy of INCB123667 plus bevacizumab in patients with recurrent solid tumors.
INCB123667 is a selective oral inhibitor of CDK2, a key regulator of cell-cycle progression that interacts with cyclin E1. During dose escalation, CCNE1 amplification was preferred, while the expansion phase required CCNE1 amplification or cyclin E1 overexpression.
Patients received oral INCB123667 at 50 mg twice daily combined with intravenous bevacizumab at 10 mg/kg every two weeks.
The analysis included 25 patients, comprising 23 with recurrent epithelial ovarian cancer and two with colon cancer. Patients with ovarian cancer had received a median of three prior lines of systemic therapy, including bevacizumab (n=19) and PARP inhibitors (n=15).
The primary objective was safety, with preliminary antitumor efficacy assessed as a secondary objective.
Key Takeaways
At the February 13, 2026, data cutoff, the combination demonstrated encouraging clinical activity in patients with recurrent epithelial ovarian cancer.
- Objective response rate: 48% (11/23; 95% CI, 26.8–69.4).
- Disease control rate: 91% (21/23; 95% CI, 72.0–98.9).
- Median time to first response: 2.0 months.
- Median duration of response: 5.6 months (95% CI, 2.1–not estimable), with responses ongoing in eight patients.
- Response durability: The estimated probability of a response lasting at least six months was 43%.
- Treatment duration: Median treatment duration was 6.2 months, with 14 patients receiving treatment for more than six months.
- Safety: All 25 patients experienced treatment-emergent adverse events (TEAEs). Grade 3–4 TEAEs occurred in 52%, while serious TEAEs were reported in 16%.
- Treatment discontinuation: No treatment discontinuations or fatal TEAEs were reported. Toxicities were managed with dose modifications.
Among the 23 patients with ovarian cancer, 21 had platinum-resistant disease, one had platinum-refractory disease, and one had platinum-sensitive disease.
Updated efficacy findings, including progression-free survival, were planned for presentation.
Conclusion
The preliminary findings demonstrated promising antitumor activity with INCB123667 plus bevacizumab in heavily pretreated recurrent epithelial ovarian cancer, including patients previously exposed to bevacizumab and PARP inhibitors.
The 48% objective response rate and 91% disease control rate suggest potential clinical activity in a population with limited treatment options. However, the small sample size, nonrandomized design, and limited follow-up require cautious interpretation.
Further clinical investigation is needed to confirm the durability of response, characterize long-term safety, and establish the potential role of CDK2 inhibition combined with bevacizumab in recurrent ovarian cancer.
Source: ESMO Congress 2026, INCB123667 Abstract; NCT05238922.
