Incyte’s CDK2 Inhibitor INCB123667 Shows Promise in Advanced Solid Tumors, Especially Ovarian Cancer

Incyte (Nasdaq:INCY) has recently shared promising early clinical data for its novel CDK2 inhibitor, INCB123667, at the European Society of Medical Oncology (ESMO) conference. This new data, highlighting the drug's potential in treating advanced solid tumors, was also discussed during an investor event hosted by the company. INCB123667 is seen as a potential first-in-class treatment for cancers characterized by increased Cyclin E1 activity, amplification, and overexpression, which suggest a dependency on CDK2.

The clinical trial involved 205 patients with advanced or metastatic solid tumors, including ovarian, endometrial, gastrointestinal, HR+/HER2- breast cancer, and triple-negative breast cancer. Participants were administered varying doses of INCB123667, ranging from 50mg to 150mg, either once daily (QD) or twice daily (BID).

The Phase 1b dose expansion part of the trial, which had a data cut-off on August 26, 2024, showed encouraging antitumor activity and reductions in circulating tumor DNA (ctDNA) across different dosages and regimens. Notably, patients with ovarian and endometrial cancers exhibiting Cyclin E1 overexpression showed significant responses. The trial is still ongoing, and researchers expect data to continue maturing.

Out of 37 evaluated participants with platinum-resistant ovarian cancer treated with selected dose levels (50mg BID, 100mg QD, and 125mg QD), nine participants (24.3%) showed an overall response (OR), including two complete responses (CR) and seven partial responses (PRs). The highest OR rate of 31.3% was recorded in the 50mg BID group, with five responders, including two CRs, among 16 evaluable participants. The disease control rate (DCR) for ovarian cancer patients was 75.7% (28/37). Additionally, four partial responses were noted among patients with endometrial cancer.

Dr. Pablo Cagnoni, President and Head of Research and Development at Incyte, expressed optimism about the early-stage clinical activity of INCB123667, especially for patients with ovarian cancer. He mentioned the drug's potential as a foundational treatment for platinum-resistant ovarian cancer, offering a new and differentiated option for patients with limited alternatives.

The data from the Phase 1b trial build on earlier results from the dose escalation phase (Part 1a), which assessed the safety and tolerability of INCB123667 and was presented at the ESMO conference. The dose escalation phase, with a data cut-off on July 15, 2024, indicated that INCB123667 has a manageable safety profile. Common hematologic treatment-related adverse events (TRAEs) included thrombocytopenia (35%, 13% Grade 3), anemia (30%, 7% Grade 3), and neutropenia (26%, 8% Grade 3). Non-hematologic TRAEs like nausea (42%), fatigue (23%), and vomiting (17%) were mostly Grade 1 and 2, with a few Grade 3 cases.

During the dose escalation phase, significant CDK2 inhibition was observed, resulting in reductions in ctDNA at all dose levels. Specifically, 39 out of 48 patients who had ctDNA measurements showed reductions.

Dr. Matteo Simonelli, Head of Early-Drug Development in Solid Tumors at IRCCS Humanitas Research Hospital, emphasized the potential of INCB123667 as a targeted therapy for various cancer types, particularly ovarian cancer. He expressed anticipation for future results as the development progresses.

The study continues, with plans to initiate a pivotal study in ovarian cancer next year and to explore the efficacy of INCB123667 in combination with other treatments.