Clinical trial NCT05238922: Study of INCB123667 in Subjects With Advanced Solid Tumors
Official title: A Phase 1, Open-Label, Multicenter Study of INCB123667 as Monotherapy and in Combination With Anticancer Therapies in Participants With Selected Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
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
Lead sponsor: Incyte Corporation
Sponsor class: INDUSTRY
First posted: 2022-02-14
Enrollment: 604
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: 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.
Primary purpose: TREATMENT

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).


Eligibility criteria: 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.

Primary outcomes:
measure: Part 1A : Occurrence of Dose Limiting Toxicities (DLTs)
timeFrame: Up to Day 28
measure: Number of Participants With Treatment Emergent Adverse Events (TEAEs)
timeFrame: Up to 12 months
measure: Number of Participants with Dose Interruptions due to TEAE
timeFrame: Up to 12 months
measure: Number of Participants who Undergo Dose Reductions due to TEAE
timeFrame: Up to 12 months
measure: Number of Participants Discontinue study due to TEAE
timeFrame: Up to 12 months
Secondary outcomes:
measure: PK parameters: Cmax
timeFrame: Cycle 1 Days 1, 2, 8 and 9; Cycle 2 Day 1; Cycles 3 through 9 Day 1 (each cycle is 28 days)
measure: PK parameters: tmax
timeFrame: Cycle 1 Days 1, 2, 8 and 9; Cycle 2 Day 1; Cycles 3 through 9 Day 1 (each cycle is 28 days)
measure: PK parameters: Ctau
timeFrame: Cycle 1 Days 1, 2, 8 and 9; Cycle 2 Day 1; Cycles 3 through 9 Day 1 (each cycle is 28 days)
measure: PK Parameters: AUC
timeFrame: Cycle 1 Days 1, 2, 8 and 9; Cycle 2 Day 1; Cycles 3 through 9 Day 1 (each cycle is 28 days)
measure: PK Parameters: CL/F
timeFrame: Cycle 1 Days 1, 2, 8 and 9; Cycle 2 Day 1; Cycles 3 through 9 Day 1 (each cycle is 28 days)
measure: PK Parameters: Vz/F
timeFrame: Cycle 1 Days 1, 2, 8 and 9; Cycle 2 Day 1; Cycles 3 through 9 Day 1 (each cycle is 28 days)
measure: PK Parameters: t1/2
timeFrame: Cycle 1 Days 1, 2, 8 and 9; Cycle 2 Day 1; Cycles 3 through 9 Day 1 (each cycle is 28 days)
measure: Objective Response Rate (ORR)
timeFrame: Up to 12 months
measure: Disease Control
timeFrame: Up to 12 months
measure: Duration of Response (DOR)
timeFrame: Up to 12 months
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope Medical Center
state: California
city: Irvine
country: United States
facility: City of Hope-Lennar Foundation Cancer Center
state: California
city: Los Angeles
country: United States
facility: Valkyrie Clinical Trials
state: California
city: Lone Tree
country: United States
facility: Rocky Mountain Cancer Centers-Sky Ridge
state: Colorado
city: New Haven
country: United States
facility: Yale Cancer Center
state: Connecticut
city: Miami Beach
country: United States
facility: Mount Sinai Medical Center Comprehensive Cancer Center
state: Florida
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: New York
country: United States
facility: New York Presbyterian/Weill Cornell
state: New York
city: Shirley
country: United States
facility: Ny Cancer and Blood Specialists
state: New York
city: Huntersville
country: United States
facility: Carolina Bio-Oncology Institute, Pllc
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Philadelphia
country: United States
facility: University of Pennsylvania Abramson Cancer Center
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Cancer Institute Cancer Services
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Allegheny Health Network
state: Pennsylvania
city: Nashville
country: United States
facility: Tennessee Oncology
state: Tennessee
city: Fort Worth
country: United States
facility: Texas Oncology-Fort Worth South Henderson
state: Texas
city: Fairfax
country: United States
facility: Virginia Cancer Institute
state: Virginia
city: Madison
country: United States
facility: University of Wisconsin
state: Wisconsin
city: Bordeaux
country: France
facility: Institut Bergonie
city: Lyon
country: France
facility: Centre Leon Berard
city: Toulouse
country: France
facility: Universitaire Du Cancer de Toulouse Institut Claudius Regaud Iuct-Oncopole
city: Villejuif Cedex
country: France
facility: Institut Gustave Roussy
city: Milan
country: Italy
facility: Fondazione Irccs Istituto Nazionale Dei Tumori
city: Naples
country: Italy
facility: Istituto Nazionale Tumori Irccs Fondazione Pascale
city: Rome
country: Italy
facility: Policlinico Universitario Agostino Gemelli Universita Cattolica Del Sacro Cuore
city: Rozzano
country: Italy
facility: Irccs Istituto Clinico Humanitas
city: Verona
country: Italy
facility: Centro Ricerche Cliniche Di Verona
city: Aichi
country: Japan
facility: Aichi Cancer Center Hospital
city: Chiba
country: Japan
facility: National Cancer Center Hospital East
city: Hidaka-shi
country: Japan
facility: Saitama Medical University International Medical Center
city: Koto-ku
country: Japan
facility: The Cancer Institute Hospital of Jfcr
city: Tokyo
country: Japan
facility: National Cancer Center Hospital
city: Amsterdam
country: Netherlands
facility: Netherlands Cancer Institute Antoni Van Leeuwenhoek Ziekenhuis
city: Rotterdam
country: Netherlands
facility: Erasmus Medical Center
city: Rio Piedras
country: Puerto Rico
facility: Panoncology Trials Pan American Center For Oncology Trials, Llc
city: Bellinzona
country: Switzerland
facility: Oncological Institute of Southern Switzerland
city: Bern
country: Switzerland
facility: Inselspital Universitatsklinik Fur Medizinische Onkologie
city: Lausanne
country: Switzerland
facility: Centre Hospitalier Universitaire Vaudois (Chuv)
city: London
country: United Kingdom
facility: Guys Hospital
city: London
country: United Kingdom
facility: Imperial College Healthcare Nhs Trust - Hammersmith Hospital
city: Newcastle Upon Tyne
country: United Kingdom
facility: Northern Centre For Cancer Care
Study officials:
affiliation: Incyte Corporation
name: Liz Croft, MD
role: STUDY_DIRECTOR
References: