Study of INCB123667 in Subjects With Advanced Solid Tumors

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

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).

Study Overview

• Status: Recruiting
• Conditions: Solid Tumors
• Intervention / Treatment: Drug: INCB0123667; Drug: Palbociclib; Drug: Fulvestrant; Drug: Ribociclib; Drug: Bevacizumab; Drug: Olaparib; Drug: Paclitaxel

• Study Type: Interventional
• Enrollment (Estimated): 604
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Incyte Corporation Call Center (US); Phone Number: 1.855.463.3463; Email: medinfo@incyte.com
• Study Contact Backup: Name: Incyte Corporation Call Center (ex-US); Phone Number: +800 00027423; Email: eumedinfo@incyte.com

Study Locations

• France
  • Bordeaux, France, 33076
    • Recruiting
    • Institut Bergonié
  • Lyon, France, 69008
    • Recruiting
    • Centre léon bérard
  • Toulouse, France, 31059
    • Recruiting
    • Universitaire Du Cancer de Toulouse Institut Claudius Regaud Iuct-Oncopole
  • Villejuif, France, 94800
    • Recruiting
    • Institut Gustave Roussy
• Italy
  • Milan, Italy, 20133
    • Recruiting
    • Fondazione IRCCS Istituto Nazionale dei Tumori
  • Naples, Italy, 80131
    • Completed
    • Istituto Nazionale Tumori IRCCS Fondazione Pascale
  • Rome, Italy, 00168
    • Recruiting
    • Policlinico Universitario Agostino Gemelli Universita Cattolica Del Sacro Cuore
  • Rozzano, Italy, 20089
    • Recruiting
    • IRCCS Istituto Clinico Humanitas
  • Verona, Italy, 37134
    • Recruiting
    • Centro Ricerche Cliniche Di Verona
• Japan
  • Aichi, Japan, 464 8681
    • Recruiting
    • Aichi Cancer Center Hospital
  • Chiba-ken, Japan, 277-0882
    • Recruiting
    • National Cancer Center Hospital East
  • Hidaka-shi, Japan, 350-1298
    • Recruiting
    • Saitama Medical University International Medical Center
  • Tokyo, Japan, 104-0045
    • Recruiting
    • National Cancer Center Hospital
  • Tokyo, Japan, 135-0063
    • Recruiting
    • The Cancer Institute Hospital of JFCR
• Netherlands
  • Amsterdam, Netherlands, 1066 CX
    • Recruiting
    • Netherlands Cancer Institute Antoni Van Leeuwenhoek Ziekenhuis
  • Rotterdam, Netherlands, 3015 GD
    • Recruiting
    • Erasmus Medical Center
• Puerto Rico
  • Rio Piedras, Puerto Rico, 00935
    • Recruiting
    • Panoncology Trials Pan American Center For Oncology Trials, Llc
• Switzerland
  • Bellinzona, Switzerland, 06500
    • Recruiting
    • Oncological Institute of Southern Switzerland
  • Bern, Switzerland, CH-3010
    • Recruiting
    • Inselspital Universitatsklinik Fur Medizinische Onkologie
  • Lausanne, Switzerland, 01011
    • Recruiting
    • Centre Hospitalier Universitaire Vaudois (CHUV)
• United Kingdom
  • London, United Kingdom, W12 0HS
    • Recruiting
    • Imperial College Healthcare NHS Trust - Hammersmith Hospital
  • London, United Kingdom, SE1 9RT
    • Recruiting
    • Guys Hospital
  • Newcastle upon Tyne, United Kingdom, NE7 7DN
    • Recruiting
    • Northern Centre for Cancer Care
• United States
  • California
    • Duarte, California, United States, 91010
      • Recruiting
      • City of Hope Medical Center
    • Irvine, California, United States, 92618
      • Recruiting
      • City of Hope-Lennar Foundation Cancer Center
    • Los Angeles, California, United States, 90067
      • Recruiting
      • Valkyrie Clinical Trials
  • Colorado
    • Lone Tree, Colorado, United States, 80124
      • Recruiting
      • Rocky Mountain Cancer Centers-Sky Ridge
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Completed
      • Yale Cancer Center
  • Florida
    • Miami Beach, Florida, United States, 33140
      • Recruiting
      • Mount Sinai Medical Center Comprehensive Cancer Center
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Completed
      • Emory University
  • New York
    • New York, New York, United States, 10022
      • Completed
      • Memorial Sloan Kettering Cancer Center
    • New York, New York, United States, 10065
      • Completed
      • New York Presbyterian/Weill Cornell
    • Shirley, New York, United States, 11967
      • Not yet recruiting
      • Ny Cancer and Blood Specialists
  • North Carolina
    • Huntersville, North Carolina, United States, 28078
      • Completed
      • Carolina Bio-Oncology Institute, Pllc
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Withdrawn
      • Cleveland Clinic
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Recruiting
      • University of Pennsylvania Abramson Cancer Center
    • Pittsburgh, Pennsylvania, United States, 15224
      • Not yet recruiting
      • Allegheny Health Network
    • Pittsburgh, Pennsylvania, United States, 15213
      • Completed
      • University of Pittsburgh Cancer Institute Cancer Services
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Not yet recruiting
      • Tennessee Oncology
  • Texas
    • Fort Worth, Texas, United States, 76104
      • Completed
      • Texas Oncology-Fort Worth South Henderson
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Recruiting
      • Virginia Cancer Institute
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • Not yet recruiting
      • University of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 95 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

21

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase 1a Dose Escalation; 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; 25 mg tablets
Experimental: Phase 1b: Dose Expansion Cohort Disease Group 2; 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; 25 mg tablets
Experimental: Phase 1b: Dose Expansion Cohort Disease Group 3; 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; 25 mg tablets
Experimental: Phase 1b: Dose Expansion Cohort Disease Group 4; 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; 25 mg tablets
Experimental: Phase 1b: Dose Expansion Cohort Disease Group 5; 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; 25 mg tablets
Experimental: Phase 1b: Dose Expansion Cohort Disease Group 1; 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; 25 mg tablets
Experimental: Phase 1b: Dose Expansion Cohort Disease Group 6; 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; 25 mg tablets
Experimental: Phase 2a Dose Escalation Treatment Group A (TGA); 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; 25 mg tablets; Drug: Palbociclib; Palbociclib will be administered at protocol defined dose.
Experimental: Phase 2a Dose Escalation Treatment Group B (TGB); 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; 25 mg tablets; Drug: Palbociclib; Palbociclib will be administered at protocol defined dose.; Drug: Fulvestrant; Fulvestrant will be administered at protocol defined dose.
Experimental: Phase 2a Dose Escalation Treatment Group C (TGC); 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; 25 mg tablets; Drug: Ribociclib; Ribociclib will be administered at protocol defined dose.
Experimental: Phase 2a Dose Escalation Treatment Group D (TGD); 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; 25 mg tablets; Drug: Fulvestrant; Fulvestrant will be administered at protocol defined dose.; Drug: Ribociclib; Ribociclib will be administered at protocol defined dose.
Experimental: Phase 2a Dose Escalation Treatment Group E (TGE); 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; 25 mg tablets; Drug: Bevacizumab; Bevacizumab will be administered at protocol defined dose.
Experimental: Phase 2a Dose Escalation Treatment Group F (TGF); 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; 25 mg tablets; Drug: Olaparib; Olaparib will be administered at protocol defined dose.
Experimental: Phase 2a Dose Escalation Treatment Group G (TGG); 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; 25 mg tablets; Drug: Paclitaxel; Paclitaxel will be administered at protocol defined dose.
Experimental: Phase 2b Dose Expansion Treatment Group H (TGH); 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; 25 mg tablets; Drug: Palbociclib; Palbociclib will be administered at protocol defined dose.
Experimental: Phase 2b Dose Expansion Treatment Group I (TGI); 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; 25 mg tablets; Drug: Palbociclib; Palbociclib will be administered at protocol defined dose.; Drug: Fulvestrant; Fulvestrant will be administered at protocol defined dose.
Experimental: Phase 2b Dose Expansion Treatment Group J (TGJ); 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; 25 mg tablets; Drug: Ribociclib; Ribociclib will be administered at protocol defined dose.
Experimental: Phase 2b Dose Expansion Treatment Group K (TGK); 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; 25 mg tablets; Drug: Fulvestrant; Fulvestrant will be administered at protocol defined dose.; Drug: Ribociclib; Ribociclib will be administered at protocol defined dose.
Experimental: Phase 2b Dose Expansion Treatment Group L (TGL); 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; 25 mg tablets; Drug: Bevacizumab; Bevacizumab will be administered at protocol defined dose.
Experimental: Phase 2b Dose Expansion Treatment Group M (TGM); 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; 25 mg tablets; Drug: Olaparib; Olaparib will be administered at protocol defined dose.
Experimental: Phase 2b Dose Expansion Treatment Group N (TGN); 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; 25 mg tablets; Drug: Paclitaxel; Paclitaxel will be administered at protocol defined dose.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR)	Defined as having a best overall Complete Response (CR) or Partial Response (PR), as determined by the investigator by radiographic disease assessment according to RECIST v1.1.	Up to 12 months
PK parameters: Cmax	Defines as the maximum (peak) plasma drug concentration	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	Defined as the time to reach maximum (peak) plasma concentration following drug administration	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	Ctau is defined as concentration at the end of the dosing interval	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	Defined as the area under the plasma concentration-time curve	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	Defined as the apparent total body clearance of the drug from plasma	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	Defined as apparent volume of distribution during terminal phase	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	Defined as Elimination half-life (to be used in one-or noncompartmental model)	Cycle 1 Days 1, 2, 8 and 9; Cycle 2 Day 1; Cycles 3 through 9 Day 1 (each cycle is 28 days)
Disease Control	Defined as having a best overall response of CR, PR, or Stable Disease (SD) as determined by the investigator by radiographic disease assessment according to RECIST v1.1.	Up to 12 months
Duration of Response (DOR)	Defined as the time from earliest date of disease response (Completed Response or Partial Response) until earliest date of disease progression as determined by the investigator by radiographic disease assessment according to RECIST v1.1 or death due to any cause if occurring sooner than progression.	Up to 12 months

Collaborators and Investigators

• Sponsor: Incyte Corporation
• Investigators: Study Director: Liz Croft, MD, Incyte Corporation

Publications and helpful links

Helpful Links

• Study of INCB123667 in Subjects with Advanced Solid Tumors

Study record dates

Study Major Dates

• Study Start (Actual): July 5, 2022
• Primary Completion (Estimated): July 27, 2027
• Study Completion (Estimated): August 31, 2027

Study Registration Dates

• First Submitted: January 31, 2022
• First Submitted That Met QC Criteria: February 9, 2022
• First Posted (Actual): February 14, 2022

Study Record Updates

• Last Update Posted (Actual): April 14, 2026
• Last Update Submitted That Met QC Criteria: April 10, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: advanced solid tumors; primary peritoneal carcinoma; metastatic solid tumors; uterine carcinosarcoma; endometrial adenocarcinoma; epithelial ovarian carcinoma; Gynecological Tumors,; GI Tumors,; Breast Cancer,; Tumor Agnostic; cyclin E1 gene; fallopian carcinoma; clear cell ovarian cancer; uterine papillary serous carcinoma; gastrointestinal tumors; gastric adenocarcinomas; GEJ adenocarcinomas; esophageal adenocarcinomas
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Endocrine System Diseases; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Neoplasms by Histologic Type; Digestive System Diseases; Genital Diseases, Female; Endocrine Gland Neoplasms; Neoplasms, Glandular and Epithelial; Ovarian Diseases; Adnexal Diseases; Genital Neoplasms, Female; Gonadal Disorders; Skin Diseases; Breast Diseases; Carcinoma; Ovarian Neoplasms; Skin and Connective Tissue Diseases; Carcinoma, Ovarian Epithelial; Breast Neoplasms; Digestive System Neoplasms; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Amino Acids, Peptides, and Proteins; Proteins; Organic Chemicals; Hydrocarbons; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Polycyclic Compounds; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Taxoids; Cyclodecanes; Diterpenes; Steroids; Fused-Ring Compounds; Estradiol; Estrenes; Estranes; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Fulvestrant; Bevacizumab; Paclitaxel; olaparib; ribociclib; palbociclib
• Other Study ID Numbers: INCB 123667-101; 2021-005357-91 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No