A Phase 2, Single-Arm Study of INCB123667 in Participants With Platinum-Resistant Ovarian Cancer With Cyclin E1 Overexpression

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Investigational drug late phase More information Active drug More information Moderate burden on patient More information

Trial Details

Sponsor: Incyte Corporation (industry)

Phase: 2

Start date: June 17, 2025

Planned enrollment: 160

Trial ID: NCT07023627
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More trial details at ClinicalTrials.gov More info

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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

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Hokkaido University Hospital

Sapporo, 060-8648, Japan

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Hyogo Cancer Center

Akashi-shi, 673-8558, Japan

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The Cancer Institute Hospital of Jfcr

Kōtoku, 135-8550, Japan

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Panoncology Trials

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Cancer Research Sa (Crsa)

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Blacktown, New South Wales, 02148, Australia

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Concord General Repatriation Hospital

Concord, New South Wales, 02139, Australia

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Adelaide, South Australia, 05065, Australia

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Hobart, Tasmania, 07000, Australia

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Cliniques Universitaires St Luc Ucl

Brussels, B-1200, Belgium

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Hopital Universitaire de Bruxelles (H.U.B)/ Academisch Ziekenhuis Brussel

Brussels, 01070, Belgium

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Universitair Ziekenhuis Leuven

Leuven, 03000, Belgium

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Kurume University Hospital

Kurume, 830-0011, Japan

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Saitama Medical University International Medical Center

Hidaka-shi, 350-1298, Japan

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Shikoku Cancer Center

Matsuyama, 791-0280, Japan

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Shizuoka Cancer Center

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Clinica Universidad de Navarra - Sede Madrid

Madrid, 28027, Spain

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Hospital Clinic de Barcelona (Hospital Clinic I Provincial)

Barcelona, 08036, Spain

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Valencia, 46010, Spain

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Girona, 17007, Spain

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Instituto Catalan de Oncologia - Hospital Duran I Reynals

Barcelona, 08908, Spain

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Instituto Valenciano de Oncologia

Valencia, 46009, Spain

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Geneva University Hospitals-Hug

Geneva, 01211, Switzerland

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Bellinzona, 06500, Switzerland

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Kantonsspital Graubunden

Chur, 07000, Switzerland

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London, SE1 9RT, United Kingdom

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Mobile, Alabama, 36604, United States

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Fort Myers, Florida, 33901, United States

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Miami, Florida, 33136, United States

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Gainesville, Georgia, 30501, United States

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Indiana University Melvin and Bren Simon Cancer Center

Indianapolis, Indiana, 46202, United States

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Parkview Research Center

Fort Wayne, Indiana, 46845, United States

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Methodist Hospital Methodist Estabrook Cancer Center

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Laura and Isaac Perlmutter Cancer Center

New York, New York, 10016, United States

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Syracuse, New York, 13210, United States

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University of Rochester, James P. Wilmot Cancer Center

Rochester, New York, 14642, United States

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Oncology Hematology Care, Inc

Cincinnati, Ohio, 45242, United States

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The Mark H Zangmeister Cancer Center Ohio

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Houston Methodist Cancer Center

Houston, Texas, 77030, United States

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Texas Oncology-Austin Center

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Texas Oncology-Tyler

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Utah Cancer Specialists

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Carilion Clinic

Roanoke, Virginia, 24016-4962, United States

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Virginia Cancer Specialists, Pc

Fairfax, Virginia, 22031, United States

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Morgantown, West Virginia, 26506, United States

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Froedtert & the Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

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Kantonsspital Baselland (Ksbl) - Standort Liestal - Medizinische Universitatsklinik

Liestal, 04410, Switzerland

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John Hopkins University-School of Medicine

Baltimore, Maryland, 21287, United States

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