INCB123667 plus bevacizumab (Avastin) induced objective responses in heavily pretreated patients with
At a median follow-up of 7.4 months, the objective response rate (ORR) was 48% (95% CI, 27%-69%) among efficacy-evaluable patients treated with the combination (n = 23); the confirmed ORR was 43% (95% CI, 23%-66%), with 10 of 11 responses confirmed. Moreover, the disease control rate (DCR) was 91% (95% CI, 72%-99%). The median duration of response (DOR) was 5.7 months (95% CI, 3.7-9.4), and the median progression-free survival (PFS) was 7.4 months (95% CI, 5.7-9.3).
Among patients whose disease progressed on a prior PARP inhibitor (n = 14), the ORR was 43% (95% CI, 18%-71%). Among those who previously received bevacizumab (n = 19), the ORR was 42% (95% CI, 20%-67%) and the confirmed ORR was 37% (95% CI, 16%-62%).
INCB123667 Plus Bevacizumab Shows Activity in Platinum-Resistant Ovarian Cancer
- INCB123667 plus bevacizumab achieved an objective response rate of 48% and a disease control rate of 91% in 23 efficacy-evaluable patients with heavily pretreated, cyclin E1–overexpressing platinum-resistant ovarian cancer.
- Antitumor activity was observed in patients whose disease progressed on prior PARP inhibitor therapy (ORR, 43%) and those previously treated with bevacizumab (ORR, 42%).
- Median duration of response was 5.7 months, and median PFS was 7.4 months.
- Grade 3 treatment-related adverse effects occurred in 52% of patients, and a phase 3 trial evaluating the combination as first-line maintenance therapy is expected to begin in 2026.
Lorusso presented the findings during a rapid oral session at the meeting.
“INCB123667, a novel, selective, oral small-molecule CDK2 inhibitor, in combination with bevacizumab, showed promising antitumor activity in heavily pretreated patients with platinum-resistant ovarian cancer and cyclin E1 overexpression,” Domenica Lorusso, MD, PhD, of Fondazione Policlinico Universitario Agostino Gemelli IRCCS in Rome and Humanitas San Pio X in Milan, Italy, said in a presentation of the data.
What has previously been reported with INCB123667?
The CDK2/cyclin E1 complex drives cell-cycle progression and DNA replication, and cyclin E1 overexpression identifies a subgroup of patients with ovarian cancer who have a poor prognosis and derive less benefit from standard therapies. INCB123667 is a selective, oral, small-molecule CDK2 inhibitor. Prior data from the phase 1 study showed that when the agent was administered as a monotherapy at a dose of 50 mg twice daily, it elicited an ORR of 31% in patients with platinum-resistant ovarian cancer.2 Moreover, when paired with bevacizumab, it enhanced tumor growth inhibition vs either agent alone in a CCNE1-amplified ovarian cancer model.1
How was the phase 1 study of INCB123667 plus bevacizumab in platinum-resistant ovarian cancer designed?
The open-label, multicenter, dose-escalation and dose-expansion phase 1 study is examining INCB123667 in combination with anticancer therapies, including bevacizumab, paclitaxel, palbociclib (Ibrance), ribociclib (Kisqali), and olaparib (Lynparza), in patients with advanced solid tumors. Patients with platinum-resistant ovarian cancer received INCB123667 at 50 mg orally twice daily plus bevacizumab at 10 mg/kg intravenously every 2 weeks in 28-day cycles, in either dose escalation (n = 3) or dose expansion (n = 20). Bevacizumab was continued until disease progression, unacceptable toxicity, or 15 months of treatment.