Incyte announces new early clinical data for INCB123667

Incyte announced new early clinical data for INCB123667, a highly selective, potential first-in-class CDK2 inhibitor, in patients with advanced solid tumors. The trial results, presented during a mini-oral presentation at the European Society of Medical Oncology with new, updated data shared during the company’s investor event, highlight the potential of INCB123667 as a differentiated treatment option for cancers with increased Cyclin E1 activity, amplification and/or overexpression in cells predictive of CDK2 dependency. In the trial, patients with advanced or metastatic solid tumors – including ovarian cancer, endometrial cancer, gastrointestinal cancer, HR+/HER2- breast cancer and triple negative breast cancer, among others – received varying doses of INCB123667 ranging from 50mg to 150mg using once-daily and twice-daily dosing schedules. New data from the Phase 1b dose expansion portion of the trial presented during Incyte’s investor event, demonstrate single-agent antitumor activity, and decreases in circulating tumor DNA across a range of doses and regimens, notably in patients with ovarian cancer and endometrial cancer whose tumors overexpress Cyclin E1. The trial is ongoing, and the data will continue to mature. Of the 37 evaluable participants with platinum-resistant ovarian cancer treated at three selected dose levels in the expansion portion of the trial, nine participants experienced an overall response. The highest OR rate of 31.3% was found in the 50mg BID cohort. Additionally, a disease control rate of 75.7% was achieved in patients with ovarian cancer. In addition, 4 PRs were reported among patients with endometrial cancer. The Part 1b data build on results from the dose escalation portion of the trial evaluating the safety and tolerability of INCB123667 presented during a mini-oral presentation at ESMO. Results from the Part 1a dose escalation portion of the trial (data cut-off July 15, 2024) include: INCB123667 demonstrated a manageable safety profile. The most common hematologic treatment-related adverse events were thrombocytopenia, anemia and neutropenia. Strong selective inhibition of CDK2 was observed resulting in circulating tumor DNA reduction at all dose levels. During dose escalation, 39 out of 48 patients who had ctDNA measurements at cycle 1, day 1 and cycle 2, day 1 showed reductions in ctDNA. The study is ongoing. Plans are underway to initiate a pivotal study in ovarian cancer next year and evaluate INCB123667 in combination with other treatments.