Solid Tumors
Conditions
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
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).
Interventions
DRUGINCB0123667
25 mg tablets
DRUGPalbociclib
Palbociclib will be administered at protocol defined dose.
DRUGBevacizumab
Bevacizumab will be administered at protocol defined dose.
DRUGOlaparib
Olaparib will be administered at protocol defined dose.
DRUGPaclitaxel
Paclitaxel will be administered at protocol defined dose.
DRUGRibociclib
Ribociclib will be administered at protocol defined dose.
DRUGFulvestrant
Fulvestrant will be administered at protocol defined dose.
Sponsors
Incyte Corporation
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
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.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
France, Italy, Japan, Netherlands, Puerto Rico, Switzerland, United Kingdom, United States
Contacts
STUDY_DIRECTORLouis Viviers, MD
Incyte Corporation
Outcome results
None listed