Sponsor: Incyte Corporation (industry)
Phase: 2
Start date: June 17, 2025
Planned enrollment: 160
INCB123667 is an oral, selective cyclin‑dependent kinase 2 (CDK2) inhibitor in development by Incyte for advanced solid tumors, with a focus on tumors that overexpress Cyclin E1 or harbor CCNE1 amplification (biomarkers of CDK2 dependency and resistance to CDK4/6 inhibitors). It is being evaluated in a first‑in‑human, multi‑part phase 1 trial as monotherapy and in combinations (NCT05238922). A pivotal study in platinum‑resistant ovarian cancer has been planned following encouraging early signals. (incyteclinicaltrials.com)
INCB123667 is a potent and highly selective small‑molecule CDK2 inhibitor with sub‑nanomolar biochemical activity against CDK2 and minimal activity on other CDKs (CDK1/4/6/7/9). In preclinical CCNE1-high breast cancer models, it suppressed RB phosphorylation (for example at Ser780), reduced S‑phase entry, induced senescence, and produced antitumor activity in xenografts, with limited weight loss. These data support targeting CDK2 in CCNE1‑amplified/overexpressing cancers. (aacrjournals.org)
Note: Detailed, peer‑reviewed efficacy analyses have not yet been published; figures above derive from conference presentations and company communications.
If additional peer‑reviewed publications or full conference manuscripts become available, efficacy and safety estimates should be updated accordingly.
Last updated: Oct 2025
Goal: Assess the antitumor activity and safety of the selective CDK2 inhibitor INCB123667 in platinum-resistant ovarian cancer characterized by Cyclin E1 (CCNE1) overexpression, using objective response by independent review 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 lines. Prior bevacizumab is required unless contraindicated; if FRα-positive, prior mirvetuximab soravtansine is required unless medically contraindicated. Archival tumor tissue within 5 years or willingness to undergo 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, single-arm, nonrandomized, multicohort study enrolling approximately 160 participants with Cyclin E1 overexpressing tumors. All participants receive INCB123667 with dosing guided by protocol-defined Cyclin E1 expression categories. Efficacy is assessed centrally by IRC per RECIST v1.1 with supportive investigator assessments and prospective safety monitoring.
Treatments: INCB123667, an oral, highly selective CDK2 inhibitor, dosed per protocol by tumor Cyclin E1 expression level across three experimental cohorts. Mechanism: potent, selective inhibition of CDK2 with preferential activity in CCNE1-high models, leading to inhibition of CDK2 substrate phosphorylation and growth arrest. Early-phase results in platinum-resistant ovarian cancer showed encouraging single-agent activity: in Phase 1, overall response rates of approximately 24% across dose levels and about 33% at 100 mg QD, with median PFS around 5 months; safety has been generally manageable with mainly hematologic and gastrointestinal adverse events. INCB123667 remains investigational and efficacy/safety are not yet established.
Outcomes: Primary: objective response rate by independent review committee per RECIST v1.1. Secondary: duration of response, progression-free survival, overall survival, objective response by investigator, and corresponding DOR and PFS by investigator, all per RECIST v1.1. Safety endpoints include incidence of treatment-emergent adverse events and TEAEs leading to dose interruptions, reductions, or discontinuation. Time frames extend up to 2 years (plus 30 days for AE follow-up).
Burden on patient: Moderate. As a single-arm oral therapy study, visit frequency is expected to be similar to standard phase 2 oncology trials, with regular clinical assessments, labs, and imaging per RECIST (typically every 6–8 to 12 weeks). A pretreatment biopsy may be required if archival tissue is unavailable, adding procedural burden. Safety monitoring for hematologic toxicity will necessitate periodic blood counts and chemistry panels; no intensive pharmacokinetic sampling schedule is described, which lowers burden relative to phase 1 designs. Travel and time commitments align with typical outpatient oral therapy trials, but central imaging assessments and potential dose modifications may increase visit frequency early in treatment.
Last updated: Oct 2025
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.
Sapporo, 060-8648, Japan
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Akashi-shi, 673-8558, Japan
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Kōtoku, 135-8550, Japan
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