On September 14, 2024 Incyte (Nasdaq:INCY) reported new early clinical data for INCB123667, a highly selective, potential first-in-class CDK2 inhibitor, in patients with advanced solid tumors (Press release, Incyte, SEP 14, 2024, View Source [SID1234646605]). The trial results, presented during a mini-oral presentation at the European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) 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.

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In the trial, patients with advanced or metastatic solid tumors (n=205) – 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 (QD) and twice-daily (BID) dosing schedules.

New data from the Phase 1b dose expansion portion of the trial (data cut-off August 26, 2024) presented today during Incyte’s investor event, demonstrate single-agent antitumor activity, and decreases in circulating tumor DNA (ctDNA) 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 (3) selected dose levels (50mg BID, 100mg QD and 125mg QD) in the expansion portion of the trial, nine participants (24.3%) experienced an overall response (OR; 2 complete responses [CR] and 7 partial responses [PRs]). The highest OR rate of 31.3% (5 responders, including 2 CRs) was found in the 50mg BID cohort (16 evaluable participants). Additionally, a disease control rate (DCR) of 75.7% (28/37) was achieved in patients with ovarian cancer.
In addition, 4 PRs were reported among patients with endometrial cancer.
"The early-stage clinical activity of INCB123667 represents an exciting and promising breakthrough for patients with ovarian cancer. 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," said Pablo Cagnoni M.D., President, Head of Research and Development, Incyte. "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."

The Part 1b data build on results from the dose escalation portion (Part 1a) of the trial evaluating the safety and tolerability of INCB123667 presented during a mini-oral presentation (Mini oral session: Developmental therapeutics) at ESMO (Free ESMO Whitepaper).

Results from the Part 1a dose escalation portion of the trial (data cut-off July 15, 2024) include:

INCB123667 demonstrated a manageable safety profile (n=84). The most common hematologic treatment-related adverse events (TRAEs) were thrombocytopenia (35%, 13% Grade 3), anemia (30%, 7% Grade 3) and neutropenia (26%, 8% Grade 3). The most common non-hematologic TRAEs were nausea (42%), fatigue (23%) and vomiting (17%); all of which were Grade 1 and 2 except one case of Grade 3 vomiting and one case of Grade 3 fatigue.
Strong selective inhibition of CDK2 was observed resulting in circulating tumor DNA (ctDNA) 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.
"Results from this study presented today at ESMO (Free ESMO Whitepaper) 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 signaling (CCNE1 amplification and Cyclin E1 overexpression), predictive of CDK2 dependency," 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."

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.

Conference Call and Webcast Information

Incyte will host an in-person analyst and investor event today from 1:00-2:30 p.m. ET (7:00-8:30 p.m. CEST) to discuss key data presentations at ESMO (Free ESMO Whitepaper) including data from the POD1UM-303 Presidential Symposia and its CDK2 inhibitor program. The CDK2 data will include updated results from a later data cut-off, as well as the data included in the ESMO (Free ESMO Whitepaper) accepted abstract and mini-oral presentation.

To access the conference call, please dial 877-407-8037 for domestic callers or +1 201-689-8037 for international callers. When prompted, provide the conference identification number, 13748627.

The conference call will also be webcast live and can be accessed at investor.incyte.com.

About the Trial (NCT05238922)

This open-label, dose-escalation and dose-expansion Phase 1 study is evaluating the safety, tolerability, pharmacokinetics, pharmacodynamics and preliminary efficacy of INCB123667 when administered as monotherapy at the recommended dose for expansion (RDE[s]) in participants with selected advanced or metastatic solid tumors. Part 1A (dose escalation) determined the recommended dose of INCB123667 for expansion and the maximum tolerated dose (MTD). Part 1B (cohort dose expansion phase) will further explore antitumor activity of INCB123667 as a monotherapy in six tumor-specific cohorts at the RDEs defined in Part 1A.

For more information about the study, please visit: View Source

About INCB123667

INCB123667 is a novel, potent and selective oral small molecule inhibitor of CDK2 which has been shown to suppress tumor growth as monotherapy and in combination with standard of care, in Cyclin E amplified tumor models. Cyclin E amplification and overexpression has been reported to be associated with CDK4/6 resistance and poor clinical outcomes in ovarian, gastric, endometrial and breast cancers. INCB123667 has the potential to be a highly targeted and efficacious treatment for advanced solid tumors, including gynecologic tumors, endometrial, uterine, gastric and triple negative breast cancer, among others.