Study of INCB123667 in Subjects With Advanced Solid Tumors

NCT05238922 | Recruiting Phase 1 FDA Drug

• 2 other identifiers: INCB 123667-1012021-005357-91
• Study Type: interventional
• Target: 604
• Locations: 8 countries
• Sites: 42

Brief 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).

Conditions

Solid Tumors

Keywords

advanced solid tumors; metastatic solid tumors; Gynecological Tumors,; GI Tumors,; Breast Cancer,; Tumor Agnostic; cyclin E1 gene; epithelial ovarian carcinoma; fallopian carcinoma; primary peritoneal carcinoma; clear cell ovarian cancer; endometrial adenocarcinoma; uterine carcinosarcoma; uterine papillary serous carcinoma; gastrointestinal tumors; gastric adenocarcinomas; GEJ adenocarcinomas; esophageal adenocarcinomas

Outcome Measures

Primary Outcomes (5)

• 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.

  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.

  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.

  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.

  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.

  Up to 12 months

Secondary Outcomes (10)

• PK parameters: Cmax

  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

  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

  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

  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

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

Study Arms (21)

Phase 1a Dose Escalation

EXPERIMENTAL

INCB123667 will be administered at a protocol defined starting regimen once daily (QD) orally in 28-day cycles. Subsequent dose regimens will be determined during study conduct.

Drug: INCB0123667

Phase 1b: Dose Expansion Cohort Disease Group 1

EXPERIMENTAL

INCB123667 will be administered at the recommended dose or doses for expansion (RDE\[s\]) for advanced or metastatic solid tumors. Participants with gynecologic tumors (epithelial ovarian/fallopian/primary peritoneal carcinoma) will enroll in this group.

Drug: INCB0123667

Phase 1b: Dose Expansion Cohort Disease Group 2

EXPERIMENTAL

INCB123667 will be administered at the recommended dose or doses for expansion (RDE\[s\]) for advanced or metastatic solid tumors. Participants with Endometrial/Uterine cancer will enroll in this group.

Drug: INCB0123667

Phase 1b: Dose Expansion Cohort Disease Group 3

EXPERIMENTAL

INCB123667 will be administered at the recommended dose or doses for expansion (RDE\[s\]) for advanced or metastatic solid tumors. Participants with gastric, Gastro Esophageal Junction (GEJ), and esophageal adenocarcinomas will enroll in this group.

Drug: INCB0123667

Phase 1b: Dose Expansion Cohort Disease Group 4

EXPERIMENTAL

INCB123667 will be administered at the recommended dose or doses for expansion (RDE\[s\]) for advanced or metastatic solid tumors. Participants with Triple Negative Breast Cancer(TNBC) will enroll in this group.

Drug: INCB0123667

Phase 1b: Dose Expansion Cohort Disease Group 5

EXPERIMENTAL

INCB123667 will be administered at the recommended dose or doses for expansion (RDE\[s\]) for advanced or metastatic solid tumors. Participants with HR+/HER2- breast cancer who have had disease progression on or been intolerant of a CDK4/6 inhibitor will enroll in this group.

Drug: INCB0123667

Phase 1b: Dose Expansion Cohort Disease Group 6

EXPERIMENTAL

INCB123667 will be administered at the recommended dose or doses for expansion (RDE\[s\]) for advanced or metastatic solid tumors will enroll in this group.

Drug: INCB0123667

Phase 2a Dose Escalation Treatment Group A (TGA)

EXPERIMENTAL

INCB123667 administered in combination with palbociclib at the recommended doses in participants with HR+/HER2- breast cancer and in participants with a different tumor as defined in the protocol.

Drug: INCB0123667; Drug: Palbociclib

Phase 2a Dose Escalation Treatment Group B (TGB)

EXPERIMENTAL

INCB123667 administered in combination with palbociclib and fulvestrant at the recommended doses in participants with HR+/HER2- breast cancer as defined in the protocol.

Drug: INCB0123667; Drug: Palbociclib; Drug: Fulvestrant

Phase 2a Dose Escalation Treatment Group C (TGC)

EXPERIMENTAL

INCB123667 administered in combination with ribociclib at the recommended doses in participants with HR+/HER2- breast cancer and in participants with a different tumor as defined in the protocol.

Drug: INCB0123667; Drug: Ribociclib

Phase 2a Dose Escalation Treatment Group D (TGD)

EXPERIMENTAL

INCB123667 administered in combination with ribociclib and fulvestrant at the recommended doses in participants with HR+/HER2- breast cancer as defined in the protocol.

Drug: INCB0123667; Drug: Ribociclib; Drug: Fulvestrant

Phase 2a Dose Escalation Treatment Group E (TGE)

EXPERIMENTAL

INCB123667 administered in combination with bevacizumab at the recommended doses in participants with HR+/HER2- breast cancer and in participants with a different tumor as defined in the protocol.

Drug: INCB0123667; Drug: Bevacizumab

Phase 2a Dose Escalation Treatment Group F (TGF)

EXPERIMENTAL

INCB123667 administered in combination with olaparib at the recommended doses in participants with HR+/HER2- breast cancer and in participants with a different tumor as defined in the protocol.

Drug: INCB0123667; Drug: Olaparib

Phase 2a Dose Escalation Treatment Group G (TGG)

EXPERIMENTAL

INCB123667 administered in combination with paclitaxel at the recommended doses in participants with HR+/HER2- breast cancer and in participants with a different tumor as defined in the protocol.

Drug: INCB0123667; Drug: Paclitaxel

Phase 2b Dose Expansion Treatment Group H (TGH)

EXPERIMENTAL

INCB123667 administered in combination with palbociclib at the recommended doses in participants with HR+/HER2- breast cancer and in participants with a different tumor as defined in the protocol.

Drug: INCB0123667; Drug: Palbociclib

Phase 2b Dose Expansion Treatment Group I (TGI)

EXPERIMENTAL

INCB123667 administered in combination with palbociclib and fulvestrant at the recommended doses in participants with HR+/HER2- breast cancer as defined in the protocol

Drug: INCB0123667; Drug: Palbociclib; Drug: Fulvestrant

Phase 2b Dose Expansion Treatment Group J (TGJ)

EXPERIMENTAL

INCB123667 administered in combination with ribociclib at the recommended doses in participants with HR+/HER2- breast cancer and in participants with a different tumor as defined in the protocol.

Drug: INCB0123667; Drug: Ribociclib

Phase 2b Dose Expansion Treatment Group K (TGK)

EXPERIMENTAL

INCB123667 administered in combination with ribociclib and fulvestrant at the recommended doses in participants with HR+/HER2- breast cancer as defined in the protocol.

Drug: INCB0123667; Drug: Ribociclib; Drug: Fulvestrant

Phase 2b Dose Expansion Treatment Group L (TGL)

EXPERIMENTAL

INCB123667 administered in combination with bevacizumab at the recommended doses in participants with gynecologic tumors (epithelial ovarian/fallopian/primary peritoneal carcinoma) as defined by the protocol.

Drug: INCB0123667; Drug: Bevacizumab

Phase 2b Dose Expansion Treatment Group M (TGM)

EXPERIMENTAL

INCB123667 administered in combination with olaparib at the recommended doses in participants with gynecologic tumors (epithelial ovarian/fallopian/primary peritoneal carcinoma) as defined by the protocol.

Drug: INCB0123667; Drug: Olaparib

Phase 2b Dose Expansion Treatment Group N (TGN)

EXPERIMENTAL

INCB123667 administered in combination with weekly paclitaxel at the recommended doses in participants with gynecologic tumors (epithelial ovarian/fallopian/primary peritoneal carcinoma) as defined by the protocol.

Drug: INCB0123667; Drug: Paclitaxel

Interventions

Palbociclib DRUG

Palbociclib will be administered at protocol defined dose.

Phase 2a Dose Escalation Treatment Group A (TGA); Phase 2a Dose Escalation Treatment Group B (TGB); Phase 2b Dose Expansion Treatment Group H (TGH); Phase 2b Dose Expansion Treatment Group I (TGI)

INCB0123667 DRUG

25 mg tablets

Phase 1a Dose Escalation; Phase 1b: Dose Expansion Cohort Disease Group 1; Phase 1b: Dose Expansion Cohort Disease Group 2; Phase 1b: Dose Expansion Cohort Disease Group 3; Phase 1b: Dose Expansion Cohort Disease Group 4; Phase 1b: Dose Expansion Cohort Disease Group 5; Phase 1b: Dose Expansion Cohort Disease Group 6; Phase 2a Dose Escalation Treatment Group A (TGA); Phase 2a Dose Escalation Treatment Group B (TGB); Phase 2a Dose Escalation Treatment Group C (TGC); Phase 2a Dose Escalation Treatment Group D (TGD); Phase 2a Dose Escalation Treatment Group E (TGE); Phase 2a Dose Escalation Treatment Group F (TGF); Phase 2a Dose Escalation Treatment Group G (TGG); Phase 2b Dose Expansion Treatment Group H (TGH); Phase 2b Dose Expansion Treatment Group I (TGI); Phase 2b Dose Expansion Treatment Group J (TGJ); Phase 2b Dose Expansion Treatment Group K (TGK); Phase 2b Dose Expansion Treatment Group L (TGL); Phase 2b Dose Expansion Treatment Group M (TGM); Phase 2b Dose Expansion Treatment Group N (TGN)

Bevacizumab DRUG

Bevacizumab will be administered at protocol defined dose.

Phase 2a Dose Escalation Treatment Group E (TGE); Phase 2b Dose Expansion Treatment Group L (TGL)

Olaparib DRUG

Olaparib will be administered at protocol defined dose.

Phase 2a Dose Escalation Treatment Group F (TGF); Phase 2b Dose Expansion Treatment Group M (TGM)

Paclitaxel DRUG

Paclitaxel will be administered at protocol defined dose.

Phase 2a Dose Escalation Treatment Group G (TGG); Phase 2b Dose Expansion Treatment Group N (TGN)

Ribociclib DRUG

Ribociclib will be administered at protocol defined dose.

Phase 2a Dose Escalation Treatment Group C (TGC); Phase 2a Dose Escalation Treatment Group D (TGD); Phase 2b Dose Expansion Treatment Group J (TGJ); Phase 2b Dose Expansion Treatment Group K (TGK)

Fulvestrant DRUG

Fulvestrant will be administered at protocol defined dose.

Phase 2a Dose Escalation Treatment Group B (TGB); Phase 2a Dose Escalation Treatment Group D (TGD); Phase 2b Dose Expansion Treatment Group I (TGI); Phase 2b Dose Expansion Treatment Group K (TGK)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:

You may not qualify if:

• 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.

Sponsors & Collaborators

• Incyte Corporation: lead

Study Sites (42)

City of Hope Medical Center

Duarte, California, 91010, United States

RECRUITING

City of Hope-Lennar Foundation Cancer Center

Irvine, California, 92618, United States

RECRUITING

Valkyrie Clinical Trials

Los Angeles, California, 90067, United States

RECRUITING

Rocky Mountain Cancer Centers-Sky Ridge

Lone Tree, Colorado, 80124, United States

RECRUITING

Yale Cancer Center

New Haven, Connecticut, 06510, United States

COMPLETED

Mount Sinai Medical Center Comprehensive Cancer Center

Miami Beach, Florida, 33140, United States

RECRUITING

Emory University

Atlanta, Georgia, 30322, United States

COMPLETED

Memorial Sloan Kettering Cancer Center

New York, New York, 10022, United States

COMPLETED

New York Presbyterian/Weill Cornell

New York, New York, 10065, United States

COMPLETED

Ny Cancer and Blood Specialists

Shirley, New York, 11967, United States

NOT YET RECRUITING

Carolina Bio-Oncology Institute, Pllc

Huntersville, North Carolina, 28078, United States

COMPLETED

Cleveland Clinic

Cleveland, Ohio, 44195, United States

WITHDRAWN

University of Pennsylvania Abramson Cancer Center

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

University of Pittsburgh Cancer Institute Cancer Services

Pittsburgh, Pennsylvania, 15213, United States

COMPLETED

Allegheny Health Network

Pittsburgh, Pennsylvania, 15224, United States

NOT YET RECRUITING

Tennessee Oncology

Nashville, Tennessee, 37203, United States

NOT YET RECRUITING

Texas Oncology-Fort Worth South Henderson

Fort Worth, Texas, 76104, United States

COMPLETED

Virginia Cancer Institute

Fairfax, Virginia, 22031, United States

RECRUITING

University of Wisconsin

Madison, Wisconsin, 53792, United States

NOT YET RECRUITING

Institut Bergonie

Bordeaux, 33076, France

RECRUITING

Centre Leon Berard

Lyon, 69008, France

RECRUITING

Universitaire Du Cancer de Toulouse Institut Claudius Regaud Iuct-Oncopole

Toulouse, 31059, France

RECRUITING

Institut Gustave Roussy

Villejuif, 94800, France

RECRUITING

Fondazione Irccs Istituto Nazionale Dei Tumori

Milan, 20133, Italy

RECRUITING

Istituto Nazionale Tumori Irccs Fondazione Pascale

Naples, 80131, Italy

COMPLETED

Policlinico Universitario Agostino Gemelli Universita Cattolica Del Sacro Cuore

Rome, 00168, Italy

RECRUITING

Irccs Istituto Clinico Humanitas

Rozzano, 20089, Italy

RECRUITING

Centro Ricerche Cliniche Di Verona

Verona, 37134, Italy

RECRUITING

Aichi Cancer Center Hospital

Aichi, 464 8681, Japan

RECRUITING

National Cancer Center Hospital East

Chiba-ken, 277-0882, Japan

RECRUITING

Saitama Medical University International Medical Center

Hidaka-shi, 350-1298, Japan

RECRUITING

National Cancer Center Hospital

Tokyo, 104-0045, Japan

RECRUITING

The Cancer Institute Hospital of Jfcr

Tokyo, 135-0063, Japan

RECRUITING

Netherlands Cancer Institute Antoni Van Leeuwenhoek Ziekenhuis

Amsterdam, 1066 CX, Netherlands

RECRUITING

Erasmus Medical Center

Rotterdam, 3015 GD, Netherlands

RECRUITING

Panoncology Trials Pan American Center For Oncology Trials, Llc

Rio Piedras, 00935, Puerto Rico

RECRUITING

Oncological Institute of Southern Switzerland

Bellinzona, 06500, Switzerland

RECRUITING

Inselspital Universitatsklinik Fur Medizinische Onkologie

Bern, CH-3010, Switzerland

RECRUITING

Centre Hospitalier Universitaire Vaudois (Chuv)

Lausanne, 01011, Switzerland

RECRUITING

Guys Hospital

London, SE1 9RT, United Kingdom

RECRUITING

Imperial College Healthcare Nhs Trust - Hammersmith Hospital

London, W12 0HS, United Kingdom

RECRUITING

Northern Centre For Cancer Care

Newcastle upon Tyne, NE7 7DN, United Kingdom

RECRUITING

Related Links

• Study of INCB123667 in Subjects with Advanced Solid Tumors

MeSH Terms

Conditions

Breast Neoplasms; Carcinoma, Ovarian Epithelial; Digestive System Neoplasms

Interventions

palbociclib; Bevacizumab; olaparib; Paclitaxel; ribociclib; Fulvestrant

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Ovarian Neoplasms; Endocrine Gland Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Estradiol; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Officials

• Liz Croft, MD

  Incyte Corporation

  STUDY DIRECTOR

Central Study Contacts

Incyte Corporation Call Center (US)

CONTACT

1.855.463.3463; medinfo@incyte.com

Incyte Corporation Call Center (ex-US)

CONTACT

+800 00027423; eumedinfo@incyte.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Part 1a and 2a will be dose escalation using a statistical hybrid design to identify the RDE(s). Parts 1b and 2b will consist of dose expansion to better characterize the safety, tolerability, PK, pharmacodynamics, and preliminary antitumor activity of INCB123667 as monotherapy or in combination with anticancer therapies.

Study Record Dates

• First Submitted: January 31, 2022
• First Posted: February 14, 2022
• Study Start: July 5, 2022
• Primary Completion (Estimated): July 27, 2027
• Study Completion (Estimated): August 31, 2027
• Last Updated: April 14, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

IT (5); NL (2); PR (1); FR (4); US (19); GB (3); JP (5); CH (3)