Study of INCB123667 in Subjects With Advanced Solid Tumors
- Conditions
- Solid Tumors
- Interventions
- Registration Number
- NCT05238922
- Lead Sponsor
- Incyte Corporation
- 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).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 604
- 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.
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Phase 2b Dose Expansion Treatment Group N (TGN) INCB0123667 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. Phase 1b: Dose Expansion Cohort Disease Group 3 INCB0123667 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. Phase 2a Dose Escalation Treatment Group B (TGB) INCB0123667 INCB123667 administered in combination with palbociclib and fulvestrant at the recommended doses in participants with HR+/HER2- breast cancer as defined in the protocol. Phase 2a Dose Escalation Treatment Group D (TGD) INCB0123667 INCB123667 administered in combination with ribociclib and fulvestrant at the recommended doses in participants with HR+/HER2- breast cancer as defined in the protocol. Phase 2a Dose Escalation Treatment Group G (TGG) INCB0123667 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. Phase 1b: Dose Expansion Cohort Disease Group 2 INCB0123667 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. Phase 1b: Dose Expansion Cohort Disease Group 4 INCB0123667 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. Phase 1b: Dose Expansion Cohort Disease Group 5 INCB0123667 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. Phase 1b: Dose Expansion Cohort Disease Group 6 INCB0123667 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. Phase 2a Dose Escalation Treatment Group A (TGA) INCB0123667 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. Phase 2a Dose Escalation Treatment Group C (TGC) INCB0123667 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. Phase 2a Dose Escalation Treatment Group E (TGE) INCB0123667 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. Phase 2a Dose Escalation Treatment Group F (TGF) INCB0123667 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. Phase 2b Dose Expansion Treatment Group H (TGH) INCB0123667 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. Phase 2b Dose Expansion Treatment Group I (TGI) INCB0123667 INCB123667 administered in combination with palbociclib and fulvestrant at the recommended doses in participants with HR+/HER2- breast cancer as defined in the protocol Phase 2b Dose Expansion Treatment Group J (TGJ) INCB0123667 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. Phase 2b Dose Expansion Treatment Group K (TGK) INCB0123667 INCB123667 administered in combination with ribociclib and fulvestrant at the recommended doses in participants with HR+/HER2- breast cancer as defined in the protocol. Phase 2b Dose Expansion Treatment Group M (TGM) INCB0123667 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. Phase 2b Dose Expansion Treatment Group L (TGL) INCB0123667 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. Phase 2b Dose Expansion Treatment Group L (TGL) Bevacizumab 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. Phase 2b Dose Expansion Treatment Group M (TGM) Olaparib 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. Phase 2b Dose Expansion Treatment Group N (TGN) Paclitaxel 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. Phase 1a Dose Escalation INCB0123667 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. Phase 1b: Dose Expansion Cohort Disease Group 1 INCB0123667 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. Phase 2a Dose Escalation Treatment Group A (TGA) Palbociclib 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. Phase 2a Dose Escalation Treatment Group B (TGB) Palbociclib INCB123667 administered in combination with palbociclib and fulvestrant at the recommended doses in participants with HR+/HER2- breast cancer as defined in the protocol. Phase 2a Dose Escalation Treatment Group B (TGB) Fulvestrant INCB123667 administered in combination with palbociclib and fulvestrant at the recommended doses in participants with HR+/HER2- breast cancer as defined in the protocol. Phase 2a Dose Escalation Treatment Group C (TGC) Ribociclib 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. Phase 2a Dose Escalation Treatment Group D (TGD) Ribociclib INCB123667 administered in combination with ribociclib and fulvestrant at the recommended doses in participants with HR+/HER2- breast cancer as defined in the protocol. Phase 2a Dose Escalation Treatment Group D (TGD) Fulvestrant INCB123667 administered in combination with ribociclib and fulvestrant at the recommended doses in participants with HR+/HER2- breast cancer as defined in the protocol. Phase 2a Dose Escalation Treatment Group E (TGE) Bevacizumab 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. Phase 2a Dose Escalation Treatment Group F (TGF) Olaparib 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. Phase 2a Dose Escalation Treatment Group G (TGG) Paclitaxel 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. Phase 2b Dose Expansion Treatment Group H (TGH) Palbociclib 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. Phase 2b Dose Expansion Treatment Group I (TGI) Palbociclib INCB123667 administered in combination with palbociclib and fulvestrant at the recommended doses in participants with HR+/HER2- breast cancer as defined in the protocol Phase 2b Dose Expansion Treatment Group I (TGI) Fulvestrant INCB123667 administered in combination with palbociclib and fulvestrant at the recommended doses in participants with HR+/HER2- breast cancer as defined in the protocol Phase 2b Dose Expansion Treatment Group J (TGJ) Ribociclib 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. Phase 2b Dose Expansion Treatment Group K (TGK) Ribociclib INCB123667 administered in combination with ribociclib and fulvestrant at the recommended doses in participants with HR+/HER2- breast cancer as defined in the protocol. Phase 2b Dose Expansion Treatment Group K (TGK) Fulvestrant INCB123667 administered in combination with ribociclib and fulvestrant at the recommended doses in participants with HR+/HER2- breast cancer as defined in the protocol.
- Primary Outcome Measures
Name Time Method Part 1A : Occurrence of Dose Limiting Toxicities (DLTs) Up to Day 28 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.
Number of Participants With Treatment Emergent Adverse Events (TEAEs) Up to 12 months 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.
Number of Participants with Dose Interruptions due to TEAE Up to 12 months 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.
Number of Participants who Undergo Dose Reductions due to TEAE Up to 12 months Participants will receive dose reductions according to lab guidelines. Treatment may be delayed for up to 2 weeks to allow for resolution of toxicity.
Number of Participants Discontinue study due to TEAE Up to 12 months 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.
- Secondary Outcome Measures
Name Time Method 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) Defines as the maximum (peak) plasma drug concentration
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) Defined as the time to reach maximum (peak) plasma concentration following drug administration
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) Ctau is defined as concentration at the end of the dosing interval
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) Defined as the area under the plasma concentration-time curve
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) Defined as the apparent total body clearance of the drug from plasma
PK Parameters: Vz/F Cycle 1 Days 1, 2, 8 and 9; Cycle 2 Day 1; Cycles 3 through 9 Day 1 (each cycle is 28 days) Defined as apparent volume of distribution during terminal phase
PK Parameters: t1/2 Cycle 1 Days 1, 2, 8 and 9; Cycle 2 Day 1; Cycles 3 through 9 Day 1 (each cycle is 28 days) Defined as Elimination half-life (to be used in one-or noncompartmental model)
Objective Response Rate (ORR) Up to 12 months 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.
Disease Control Up to 12 months 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.
Duration of Response (DOR) Up to 12 months 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.
Related Research Topics
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Trial Locations
- Locations (43)
City of Hope Medical Center
🇺🇸Duarte, California, United States
City of Hope-Lennar Foundation Cancer Center
🇺🇸Irvine, California, United States
Valkyrie Clinical Trials
🇺🇸Los Angeles, California, United States
Rocky Mountain Cancer Centers-Sky Ridge
🇺🇸Lone Tree, Colorado, United States
Yale Cancer Center
🇺🇸New Haven, Connecticut, United States
Mount Sinai Medical Center Comprehensive Cancer Center
🇺🇸Miami Beach, Florida, United States
Emory University
🇺🇸Atlanta, Georgia, United States
Hackensack University Medical Center
🇺🇸Hackensack, New Jersey, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
New York Presbyterian/Weill Cornell
🇺🇸New York, New York, United States
Scroll for more (33 remaining)City of Hope Medical Center🇺🇸Duarte, California, United States