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RecruitingInterventionalPhase 1

A Phase 1, Open-Label, Multicenter Study of INCB123667 as Monotherapy and in Combination With Anticancer Therapies in Participants With Selected Advanced Solid Tumors

NCT ID: NCT05238922Sponsor: Incyte CorporationLast updated: 2026-04-14

Summary

This is an open-label, dose-escalation and dose-expansion study to determine the safety, tolerability, PK, pharmacodynamics, and preliminary efficacy of INCB123667 when administered as monotherapy and in combination with anticancer therapies in participants with selected advanced or metastatic solid tumors. This study will consist of 2 parts. In Part 1, INCB123667 will be administered as monotherapy and in Part 2, INCB123667 will be administered in combination with anticancer therapies of interest. Each part will comprise a dose escalation portion (Parts 1a and 2a, respectively) and a dose-expansion portion (Parts 1b and 2b, respectively).

Arms & interventions

  • DrugINCB0123667

    25 mg tablets

  • DrugPalbociclib

    Palbociclib will be administered at protocol defined dose.

  • DrugBevacizumab

    Bevacizumab will be administered at protocol defined dose.

  • DrugOlaparib

    Olaparib will be administered at protocol defined dose.

  • DrugPaclitaxel

    Paclitaxel will be administered at protocol defined dose.

  • DrugRibociclib

    Ribociclib will be administered at protocol defined dose.

  • DrugFulvestrant

    Fulvestrant will be administered at protocol defined dose.

Outcome measures

Primary

  • Part 1A : Occurrence of Dose Limiting Toxicities (DLTs)

    Toxicities occurring during the first treatment cycle, Part 1a, will define tolerability. DLTs will be assessed for severity by the investigator using CTCAE v5.0 criteria.

    Time frame: Up to Day 28

  • Number of Participants With Treatment Emergent Adverse Events (TEAEs)

    TEAE is any Adverse Event (AE) either reported for the first time or worsening of a pre-existing event after first dose of study drug.

    Time frame: Up to 12 months

  • Number of Participants with Dose Interruptions due to TEAE

    Participants will receive dose reductions of INCB123667 according to lab guidelines. Treatment may be delayed for up to 2 weeks to allow for resolution of toxicity.

    Time frame: Up to 12 months

  • Number of Participants who Undergo Dose Reductions due to TEAE

    Participants will receive dose reductions according to lab guidelines. Treatment may be delayed for up to 2 weeks to allow for resolution of toxicity.

    Time frame: Up to 12 months

  • Number of Participants Discontinue study due to TEAE

    TEAE is defined as any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment.

    Time frame: Up to 12 months

Secondary

  • PK parameters: Cmax

    Time frame: Cycle 1 Days 1, 2, 8 and 9; Cycle 2 Day 1; Cycles 3 through 9 Day 1 (each cycle is 28 days)

  • PK parameters: tmax

    Time frame: Cycle 1 Days 1, 2, 8 and 9; Cycle 2 Day 1; Cycles 3 through 9 Day 1 (each cycle is 28 days)

  • PK parameters: Ctau

    Time frame: Cycle 1 Days 1, 2, 8 and 9; Cycle 2 Day 1; Cycles 3 through 9 Day 1 (each cycle is 28 days)

  • PK Parameters: AUC

    Time frame: Cycle 1 Days 1, 2, 8 and 9; Cycle 2 Day 1; Cycles 3 through 9 Day 1 (each cycle is 28 days)

  • PK Parameters: CL/F

    Time frame: Cycle 1 Days 1, 2, 8 and 9; Cycle 2 Day 1; Cycles 3 through 9 Day 1 (each cycle is 28 days)

  • PK Parameters: Vz/F

    Time frame: Cycle 1 Days 1, 2, 8 and 9; Cycle 2 Day 1; Cycles 3 through 9 Day 1 (each cycle is 28 days)

  • PK Parameters: t1/2

    Time frame: Cycle 1 Days 1, 2, 8 and 9; Cycle 2 Day 1; Cycles 3 through 9 Day 1 (each cycle is 28 days)

  • Objective Response Rate (ORR)

    Time frame: Up to 12 months

  • Disease Control

    Time frame: Up to 12 months

  • Duration of Response (DOR)

    Time frame: Up to 12 months

Eligibility criteria

Sex: AllAge: 18 Years and olderHealthy volunteers: No
Inclusion Criteria: * Adults aged 18 years or older at the time of the signing of the ICF. * Life expectancy greater than 12 weeks. * ECOG performance status score of 0 or 1. * Disease progression on prior standard treatment, intolerance to or ineligibility for standard treatment, or no available treatment to improve the disease outcome. * Availability of a baseline archival tumor specimen or willingness to undergo a pretreatment and an on-treatment tumor biopsy. For Part 1: Participants in Part 1A (dose escalation): Histologically or cytologically confirmed advanced or metastatic solid tumors. Participants in Part 1B (dose expansion): * Disease Group 1: Ovarian/Fallopian/Primary Peritoneal Cancer * Disease Group 2: Endometrial/Uterine Cancer * Disease Group 3: Gastric, GEJ, and esophageal carcinomas * Disease Group 4: TNBC * Disease Group 5: HR+/HER2- breast cancer * Disease Group 6: Other tumor indications excluding bone cancers For Part 2: Participants in Part 2A (dose escalation): Histologically or cytologically confirmed advanced or metastatic solid tumors. * TGA, TGC, TGE, TGF, and TGG: Participants with HR+/HER2- breast cancer or participants with a different tumor. * TGB and TGD: Participants with HR+/HER2- breast cancer. Participants in Part 2b (dose expansion): * TGH and TGJ: * Participants with HR+/HER2- breast cancer. * Participants with any other advanced or metastatic solid tumor. * TGI and TGK: • Participants with HR+/HER2- breast cancer. * TGL, TGM and TGN: • Participants with advanced or metastatic epithelial ovarian/fallopian/primary peritoneal carcinoma. * Measurable lesions by CT or MRI based on RECIST v1.1 criteria. Exclusion Criteria: * History of clinically significant or uncontrolled cardiac disease. * History or presence of an ECG abnormality that, in the investigator's opinion, is clinically meaningful. * Presence of chronic or current active infectious disease requiring systemic antibiotic, antifungal, or antiviral treatment. * Untreated brain or central nervous system (CNS) metastases or brain or CNS metastases that have progressed. * Known additional malignancy that is progressing or requires active treatment, or history of other malignancy within 2 years of the first dose of study drug. * Specific laboratory values. * Significant concurrent, uncontrolled medical conditions, including but not limited to Hepatic and Gastrointestinal. * Has not recovered to ≤ Grade 1 from toxic effects of prior therapy and/or complications from prior surgical intervention before starting study drug. * Prior treatment with any CDK2 inhibitor. * Any change in endocrine therapy within 5 half-lives or 28 days (whichever is shorter) before the first dose of study drug or any administration of targeted therapy, antibody, or hypomethylating agent to treat the participant's disease within 5 half-lives or 28 days (whichever is shorter) before the first dose of study drug. * Any major surgery within 28 days before the first dose of study drug. * Any prior radiation therapy within 28 days before the first dose of study drug. * Undergoing treatment with another investigational medication or having been treated with an investigational medication within 5 half-lives or 28 days (whichever is shorter) before the first dose of study drug. * Active HBV or HCV infection that requires treatment. * Known history of HIV. * Known hypersensitivity or severe reaction to any component of study treatment or formulation components. Other protocol-defined Inclusion/Exclusion Criteria may apply.

Study locations (19)

City of Hope Medical Center

Duarte, California, 91010

Recruiting

City of Hope-Lennar Foundation Cancer Center

Irvine, California, 92618

Recruiting

Valkyrie Clinical Trials

Los Angeles, California, 90067

Recruiting

Rocky Mountain Cancer Centers-Sky Ridge

Lone Tree, Colorado, 80124

Recruiting

Yale Cancer Center

New Haven, Connecticut, 06510

Completed

Mount Sinai Medical Center Comprehensive Cancer Center

Miami Beach, Florida, 33140

Recruiting

Emory University

Atlanta, Georgia, 30322

Completed

Memorial Sloan Kettering Cancer Center

New York, New York, 10022

Completed

New York Presbyterian/Weill Cornell

New York, New York, 10065

Completed

Ny Cancer and Blood Specialists

Shirley, New York, 11967

Not Yet Recruiting

Carolina Bio-Oncology Institute, Pllc

Huntersville, North Carolina, 28078

Completed

Cleveland Clinic

Cleveland, Ohio, 44195

Withdrawn

University of Pennsylvania Abramson Cancer Center

Philadelphia, Pennsylvania, 19104

Recruiting

University of Pittsburgh Cancer Institute Cancer Services

Pittsburgh, Pennsylvania, 15213

Completed

Allegheny Health Network

Pittsburgh, Pennsylvania, 15224

Not Yet Recruiting

Tennessee Oncology

Nashville, Tennessee, 37203

Not Yet Recruiting

Texas Oncology-Fort Worth South Henderson

Fort Worth, Texas, 76104

Completed

Virginia Cancer Institute

Fairfax, Virginia, 22031

Recruiting

University of Wisconsin

Madison, Wisconsin, 53792

Not Yet Recruiting