Study of INCB123667 in Subjects With Advanced Solid Tumors

Solid Tumors Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05238922
• Other study ID #: INCB 123667-101
• Status: Recruiting
• Phase: Phase 1
• Start date: July 5, 2022
• Est. completion date: July 30, 2026

Study information

• Verified date: December 2023
• Source: Incyte Corporation
• Contact: Incyte Corporation Call Center (US)
• Phone: 1.855.463.3463
• Email: medinfo[@]incyte.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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 at the RDE(s) in participants with selected advanced or metastatic solid tumors. Part 1A (dose escalation) will determine the recommended dose of INCB123667 for expansion (RDE) and the maximum tolerated dose (MTD). Part 1B (cohort dose expansion phase) will further explore antitumor activity of INCB123667 as a monotherapy in 6 tumor-specific cohorts at the RDE(s) defined in Part 1A.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 340
• Est. completion date: July 30, 2026
• Est. primary completion date: April 27, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• France Only : Adults age of at least 18 and up to 99 years.

• 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 (core or excisional) as applicable to obtain the specimen.

Participants in Part 1B:

• Disease Group 1 : Ovarian/Fallopian/Primary Peritoneal Cancer

• Disease Group 2 : Endometrial/Uterine Cancer

• Disease Group 3: Gastric, GEJ, and esophageal adeno-carcinomas

• Disease Group 4 : TNBC

• Disease Group 5: Breast cancer (HR+/HER-)

• Disease Group 6: Other tumor indications

• Measurable lesions by CT or MRI based on RECIST v1.1 criteria that are considered nonamenable to surgery or other curative treatments or procedures.

• Willingness to avoid pregnancy or fathering children.

Exclusion Criteria:

• History of clinically significant or uncontrolled cardiac disease, including recent (within the last 12 months) unstable angina pectoris or acute myocardial infarction, or New York Heart Association Class III or IV cardiac disease, including preexisting clinically significant ventricular arrhythmia, congestive heart failure, cardiomyopathy not controlled by medication, or other clinically significant heart disease (ie, = uncontrolled Grade 3 hypertension).

• History or presence of an ECG abnormality that, in the investigator's opinion, is clinically meaningful. Screening QTcF interval > 450 milliseconds is excluded; in the event that a single QTc is > 450 milliseconds, the participant may enroll if the average QTc for the 3 ECGs is < 450 milliseconds.

• 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 (eg, evidence of new or enlarging brain metastasis or new neurological symptoms attributable to brain or CNS metastases).

• 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 with the exception of cured basal cell or squamous cell carcinoma of the skin, superficial bladder cancer, prostate intraepithelial neoplasm, carcinoma in situ of the cervix, or other noninvasive or indolent malignancy, or cancers from which the participant has been disease-free for > 1 year after treatment with curative intent.

• Specific Lab values

• Significant concurrent, uncontrolled medical conditions, such as liver disease and gastrointestinal disorders.

• 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.

• Undergoing treatment with any potent CYP3A4/CYP3A5 inhibitor or inducer (University of Washington School of Pharmacy 2020) or having been treated with a potent CYP3A4/CYP3A5 inhibitor or inducer within 5 half-lives or 28 days (whichever is shorter) before the first dose of study drug.

• Known or suspected SARS-CoV-2 infection at the time of enrollment.

• Active HBV or HCV infection that requires treatment. HBV DNA and HCV RNA must be undetectable. Participants who have cleared a prior HBV infection (defined as HBsAg negative, HBsAg antibody positive, and anti-HBc antibody positive) are eligible for the study.

• Known history of HIV (HIV 1/2 antibodies).

• Known hypersensitivity or severe reaction to any component of study drug(s) or formulation components.

• Chronic or current active infectious disease requiring systemic antibiotics, antifungal, or antiviral treatment.

• Current use of certain prohibited medications.

• Women who are pregnant or breastfeeding.

• For studies conducted in France, the following participants are excluded: vulnerable populations according to article L.1121-6 of the French Public Health Code and adults under legal protection or who are unable to express their consent per article L.1121-8 of the French Public Health Code.

Related Conditions & MeSH terms

• Neoplasms
• Solid Tumors

Intervention

Drug:
• INCB0123667
25 mg tablets

Locations

Country	Name	City	State
France	Institut Bergonie	Bordeaux
France	Centre Leon Berard	Lyon
France	Universitaire Du Cancer de Toulouse Institut Claudius Regaud Iuct-Oncopole	Toulouse
France	Institut Gustave Roussy	Villejuif
Italy	Fondazione Irccs Istituto Nazionale Del Tumori Di Milano	Milan
Italy	Istituto Nazionale Tumori Irccs Fondazione Pascale	Naples
Italy	Policlinico Universitario Agostino Gemelli Universita Cattolica Del Sacro Cuore	Rome
Italy	Irccs Istituto Clinico Humanitas	Rozzano
Italy	Centro Ricerche Cliniche Di Verona (Crc)	Verona
Japan	Aichi Cancer Center Hospital	Aichi
Japan	National Cancer Center Hospital East	Chiba-ken
Japan	Saitama Medical University International Medical Center	Hidaka-shi
Japan	The Cancer Institute Hospital of Jfcr	Koto-ku
Japan	National Cancer Center Hospital	Tokyo
Netherlands	Netherlands Cancer Institute Antoni Van Leeuwenhoek Ziekenhuis	Amsterdam
Netherlands	Erasmus Medical Center	Rotterdam
Switzerland	Oncological Institute of Southern Switzerland	Bellinzona
Switzerland	Inselspital Universitatsklinik Fur Medizinische Onkologie	Bern
Switzerland	Centre Hospitalier Universitaire Vaudois (Chuv)	Lausanne
United Kingdom	Western General Hospital	Edinburgh
United Kingdom	Guys Hospital	London
United Kingdom	Imperial College Healthcare Nhs Trust - Hammersmith Hospital	London
United Kingdom	Northern Centre For Cancer Care	Newcastle Upon Tyne
United States	Emory University	Atlanta	Georgia
United States	City of Hope Medical Center	Duarte	California
United States	Texas Oncology-Fort Worth South Henderson	Fort Worth	Texas
United States	Carolina Bio-Oncology Institute, Pllc	Huntersville	North Carolina
United States	City of Hope-Lennar Foundation Cancer Center	Irvine	California
United States	Rocky Mountain Cancer Centers-Sky Ridge	Lone Tree	Colorado
United States	Yale Cancer Center	New Haven	Connecticut
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	New York Presbyterian/Weill Cornell	New York	New York
United States	University of Pennsylvania Abramson Cancer Center	Philadelphia	Pennsylvania
United States	University of Pittsburgh Cancer Institute Cancer Services	Pittsburgh	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Incyte Corporation

Countries where clinical trial is conducted

United States,  France,  Italy,  Japan,  Netherlands,  Switzerland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
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.	Up to Day 28
Primary	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
Primary	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
Primary	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
Primary	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	PK parameters: Cmax	Defines as the maximum (peak) plasma drug concentration	Cycle 1 Days 1, 8, and 15; Cycle 2 Days 1 and 8 (each cycle is 28 days)
Secondary	PK parameters: tmax	Defined as the time to reach maximum (peak) plasma concentration following drug administration	Cycle 1 Days 1, 8, and 15; Cycle 2 Days 1 and 8 (each cycle is 28 days)
Secondary	PK parameters: Ctau	Ctau is defined as concentration at the end of the dosing interval	Cycle 1 Days 1, 8, and 15; Cycle 2 Days 1 and 8 (each cycle is 28 days)
Secondary	PK Parameters: AUC	Defined as the area under the plasma concentration-time curve	Cycle 1 Days 1, 8, and 15; Cycle 2 Days 1 and 8 (each cycle is 28 days)
Secondary	PK Parameters: CL (or CL/F)	Defined as the apparent total body clearance of the drug from plasma	Cycle 1 Days 1, 8, and 15; Cycle 2 Days 1 and 8 (each cycle is 28 days)
Secondary	PK Parameters: Vz (or Vz/F)	Defined as apparent volume of distribution during terminal phase	Cycle 1 Days 1, 8, and 15; Cycle 2 Days 1 and 8 (each cycle is 28 days)
Secondary	PK Parameters: t1/2	Defined as Elimination half-life (to be used in one-or noncompartmental model)	Cycle 1 Days 1, 8, and 15; Cycle 2 Days 1 and 8 (each cycle is 28 days)
Secondary	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
Secondary	Disease Control Response (DCR)	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
Secondary	Duration of Response (DOR)	Defined as the time from earliest date of disease response (Completed Rresponse 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