Incyte has revealed promising early clinical data for its potential first-in-class CDK2 inhibitor, INCB123667, in patients with advanced solid tumours. The data, presented at the European Society of Medical Oncology (ESMO) Congress 2024 and updated during the company’s investor event, highlight the drug’s potential as a novel treatment option for cancers driven by elevated Cyclin E1 activity.
The ongoing Phase 1b trial includes patients with ovarian, endometrial, gastrointestinal, and breast cancers, among others. The trial focuses on assessing the safety and efficacy of INCB123667 across varying doses and regimens. The latest results, based on a data cut-off from August 2024, show encouraging antitumor activity, particularly in ovarian and endometrial cancers, where tumours overexpress Cyclin E1.
Dr Pablo Cagnoni, President and Head of Research and Development at Incyte, described the findings as an “exciting breakthrough” for patients with platinum-resistant ovarian cancer, a group with limited treatment options. “We believe this novel CDK2 inhibitor has the potential to be a foundational treatment for ovarian cancer, both as a single agent and in combination with other therapies,” he said.
Promising Results in Ovarian Cancer
The trial, which enrolled 205 patients with advanced or metastatic solid tumours, tested a range of doses between 50mg and 150mg, administered either once or twice daily. Among the 37 patients with platinum-resistant ovarian cancer, an overall response rate (ORR) of 24.3% was observed. This included two complete responses and seven partial responses. The highest response rate of 31.3% was recorded in the 50mg twice-daily dosing group. In addition, a disease control rate (DCR) of 75.7% was achieved in ovarian cancer patients.
Patients with endometrial cancer also showed notable responses, with four participants achieving partial responses.
The early data suggest that INCB123667 could be particularly effective in tumours with Cyclin E1 amplification and overexpression, which are predictive of CDK2 dependency. This positions the drug as a potential targeted therapy for a range of cancers where these genetic markers are present.
Manageable Safety Profile
In the earlier Phase 1a dose-escalation part of the trial, INCB123667 demonstrated a manageable safety profile. Common hematologic adverse events included thrombocytopenia (35%), anaemia (30%), and neutropenia (26%). Non-hematologic side effects included nausea, fatigue, and vomiting, most of which were low-grade. Importantly, strong selective inhibition of CDK2 was observed, with significant reductions in circulating tumour DNA (ctDNA) seen across all dose levels.
Dr Matteo Simonelli, Head of Early-Drug Development in Solid Tumours at IRCCS Humanitas Research Hospital, praised the study’s results: “The data speak to the potential of INCB123667 as an active and selective targeted therapy for different cancer types, particularly ovarian cancer. I look forward to seeing further results in later stages of development.”
Pivotal Trial to Begin in 2025
Building on the success of the ongoing trial, Incyte plans to launch a pivotal study in ovarian cancer next year. Additionally, the company is exploring the potential of combining INCB123667 with other therapies to enhance treatment outcomes in patients with advanced cancers.
Incyte’s investor event included a live webcast, where company representatives discussed the latest data and outlined future plans for the CDK2 inhibitor programme.
The webcast and further details can be accessed at investor.incyte.com.