Sponsor: Incyte Corporation (industry)
Phase: 2
Start date: June 17, 2025
Planned enrollment: 160
INCB123667 is an investigational, oral, highly selective cyclin‑dependent kinase 2 (CDK2) inhibitor being developed by Incyte for advanced solid tumors characterized by Cyclin E1 (CCNE1) amplification/overexpression. Early human data show single‑agent antitumor activity—particularly in platinum‑resistant ovarian cancer—and a generally manageable safety profile. A Phase 2 study in platinum‑resistant ovarian cancer with Cyclin E1 overexpression is initiating, and a food‑effect PK study in healthy adults has completed. (oncologypro.esmo.org, businesswire.com, incyteclinicaltrials.com, ichgcp.net)
Note: A Phase 2, single‑arm study in platinum‑resistant ovarian cancer with Cyclin E1 overexpression (INCB123667‑203; NCT07023627) is planned to evaluate objective response by independent review, with estimated study dates August 2025 to October 2027. (incyteclinicaltrials.com, ichgcp.net)
Disclaimer: INCB123667 is investigational; efficacy and safety have not been established and the program is ongoing. Figures above reflect interim analyses at the stated data cutoffs.
Last updated: Sep 2025
Goal: Evaluate the antitumor activity and safety of the selective CDK2 inhibitor INCB123667 in platinum-resistant ovarian cancer with Cyclin E1 overexpression, using independently reviewed objective response as the primary endpoint.
Patients: Adults with histologically confirmed high-grade serous epithelial ovarian, fallopian tube, or primary peritoneal cancer with platinum-resistant disease after 1–4 prior systemic regimens, prior bevacizumab required unless contraindicated, and prior mirvetuximab soravtansine required if tumor is FRα-positive unless medically contraindicated. Archival tumor tissue within 5 years or willingness for pretreatment biopsy is required. Key exclusions include non–high-grade serous histologies, primary platinum-refractory disease, untreated/active CNS metastases, significant recent cardiac disease, and other active malignancies.
Design: Phase 2, multicohort, single-arm, nonrandomized study enrolling approximately 160 participants. All cohorts receive INCB123667 with dosing guided by tumor Cyclin E1 expression; efficacy is assessed by independent review per RECIST v1.1.
Treatments: INCB123667, an oral, highly selective CDK2 inhibitor designed for tumors characterized by CCNE1 amplification/overexpression. CDK2 inhibition aims to counter Cyclin E–driven cell-cycle progression, with pharmacodynamic evidence of CDK2 substrate inhibition and growth arrest in CCNE1-high models. Early clinical data from Phase 1a/1b suggest single-agent activity in platinum-resistant ovarian cancer, with reported objective response rates around 24–33% in expansion cohorts and a generally manageable safety profile predominantly featuring low-grade hematologic and gastrointestinal events. In this study, INCB123667 is dosed per protocol stratified by cyclin E1 expression across three experimental cohorts.
Outcomes: Primary: Objective response by independent review committee (RECIST v1.1). Secondary: Duration of response, progression-free survival, objective response by investigator, duration of response by investigator, progression-free survival by investigator, overall survival, and safety including treatment-emergent adverse events and events leading to dose modifications or discontinuation. All time-to-event endpoints are followed for up to approximately 2 years.
Burden on patient: Moderate. The trial uses an oral agent, which typically reduces clinic time, but requires baseline tumor tissue submission and may necessitate a pretreatment biopsy if archival tissue is unavailable. Regular radiographic assessments for RECIST-based independent review, clinical evaluations, laboratory monitoring, and safety surveillance are anticipated at a frequency similar to other phase 2 oncology studies (for example, imaging every 6–9 weeks). No intensive pharmacokinetic sampling is indicated, but potential dose modifications and monitoring for hematologic toxicity may add visit frequency early in treatment. Travel and visit burden should be comparable to other single-agent phase 2 studies in the platinum-resistant setting.
Inclusion Criteria:
* Histological diagnosis of a high-grade serous epithelial ovarian, fallopian tube, or primary peritoneal cancer.
* Have platinum-resistant disease:
* Participants who have only had 1 line of platinum-based therapy must have received at least 4 cycles of a platinum-containing regimen.
* Participants who have received 2 to 4 lines of platinum-based therapy must have progressed on or within 6 months after the last dose of platinum.
* Archival FFPE tumor tissue block or slides from a specimen no older than 5 years must be available. If not available, participant must be willing to undergo a pretreatment tumor biopsy.
* Received at least 1 and no more than 4 prior lines of systemic therapy following the initial diagnosis, after which single-agent therapy is considered an appropriate next therapeutic option.
* Must have received bevacizumab unless there was a contraindication for its use.
* If the tumor tests positive for FRα, participants must have received mirvetuximab soravtansine unless there is an exception for its use on medical grounds.
Exclusion Criteria:
* Have endometrioid, clear cell, mucinous, or sarcomatous histology, mixed tumors containing any of these histologies, or low-grade/borderline ovarian cancer.
* Have primary platinum-refractory disease: either did not respond (CR or PR) to first-line platinum-containing therapy or progressed on or within 3 months after the last dose of the first line platinum-containing therapy.
* The tumor tests positive for FRα but the participant has not received mirvetuximab soravtansine for any reason other than medical contraindication.
* Clinically significant or uncontrolled cardiac disease within 6 months before the first dose of study drug.
* Known active CNS metastases and/or carcinomatous meningitis.
* Known additional malignancy that is progressing or requires active treatment.
Other protocol-defined Inclusion/Exclusion Criteria may apply.
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