New data from Incyte highlights efficacy of CDK2 inhibitor in ovarian cancer; Pivotal trials expected in 2025

Incyte has announced new early-stage clinical data for INCB123667, a highly selective and potential first-in-class CDK2 inhibitor, showing promising results in patients with advanced solid tumors, particularly ovarian cancer. The data were presented during the European Society of Medical Oncology (ESMO) Congress 2024 and later updated during an Incyte investor event, emphasising the potential of INCB123667 as a differentiated treatment option for cancers with increased Cyclin E1 activity, amplification, or overexpression.

The Phase 1b dose expansion trial results indicate significant antitumor activity and decreases in circulating tumor DNA (ctDNA) across various doses and regimens, especially in patients with ovarian and endometrial cancer whose tumors overexpress Cyclin E1. Among 37 evaluable participants with platinum-resistant ovarian cancer, nine participants (24.3%) experienced an overall response, with two complete responses and seven partial responses. Notably, the 50mg BID cohort demonstrated the highest overall response rate of 31.3%, including two complete responses among 16 evaluable participants. The disease control rate for ovarian cancer patients was 75.7%, highlighting the drug’s potential effectiveness.

In addition to ovarian cancer, four partial responses were observed in patients with endometrial cancer. These results suggest that INCB123667 could become a foundational treatment for ovarian cancer, especially in cases resistant to platinum-based therapies.

“The early-stage clinical activity of INCB123667 represents an exciting and promising breakthrough for patients with ovarian cancer,” said Pablo Cagnoni, President and Head of Research and Development at Incyte. “We believe this novel CDK2 inhibitor has the potential to be a foundational treatment for platinum-resistant ovarian cancer, offering a new and differentiated treatment for patients who currently have limited treatment options. We look forward to advancing the development of INCB123667 for the treatment of patients with ovarian cancer both as a single agent and in combination.”

Safety Profile and Future Development Plans

The Phase 1b data build upon results from the dose escalation portion (Part 1a) of the trial, which focused on evaluating the safety and tolerability of INCB123667. The trial results presented during a mini-oral presentation at ESMO showed that INCB123667 has a manageable safety profile. The most common hematologic treatment-related adverse events were thrombocytopenia (35%), anemia (30%), and neutropenia (26%). Non-hematologic adverse events included nausea (42%), fatigue (23%), and vomiting (17%), with most cases being mild to moderate in severity.

Results from the dose escalation study (Part 1a) demonstrated strong selective inhibition of CDK2, leading to reductions in ctDNA at all dose levels. Of the 48 patients who had ctDNA measurements at specific cycles, 39 showed reductions, reinforcing the potential efficacy of INCB123667.

“Results from this study presented today at ESMO reinforce the idea that the novel and highly selective CDK2 inhibitor INCB123667 may provide a potential new treatment option for cancers with increased Cyclin E1 signalling,” said Dr Matteo Simonelli, Head of Early-Drug Development in Solid Tumors at IRCCS Humanitas Research Hospital. “The data speak to the potential of INCB123667 as an active and selective targeted therapy for different cancer types, particularly ovarian cancer, and I look forward to seeing further results in later stages of development.”

Pivotal Trials and Combination Therapy Plans

Given the promising early results, Incyte plans to initiate a pivotal study in ovarian cancer in 2025. Additionally, there are plans to evaluate INCB123667 in combination with other treatments, potentially enhancing its therapeutic impact. The ongoing open-label, dose-escalation and dose-expansion Phase 1 study is set to further explore the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy of INCB123667 as monotherapy in selected advanced or metastatic solid tumors.

INCB123667 is an oral small molecule inhibitor of CDK2 that has shown the ability to suppress tumor growth both as a monotherapy and in combination with standard care in Cyclin E amplified tumor models. Cyclin E amplification and overexpression have been associated with CDK4/6 resistance and poor clinical outcomes in cancers such as ovarian, gastric, endometrial, and breast cancers. INCB123667’s targeted approach makes it a potentially efficacious treatment for these advanced solid tumors.