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 Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
604
25 mg tablets
Palbociclib will be administered at protocol defined dose.
Bevacizumab will be administered at protocol defined dose.
Olaparib will be administered at protocol defined dose.
Paclitaxel will be administered at protocol defined dose.
Ribociclib will be administered at protocol defined dose.
Fulvestrant will be administered at protocol defined dose.
City of Hope Medical Center
Duarte, California, United States
RECRUITINGCity of Hope-Lennar Foundation Cancer Center
Irvine, California, United States
RECRUITINGValkyrie Clinical Trials
Los Angeles, California, United States
RECRUITINGRocky Mountain Cancer Centers-Sky Ridge
Lone Tree, Colorado, United States
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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: Up to 12 months
PK parameters: Cmax
Defines as the maximum (peak) plasma drug concentration
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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)
Time frame: Cycle 1 Days 1, 2, 8 and 9; Cycle 2 Day 1; Cycles 3 through 9 Day 1 (each cycle is 28 days)
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.
Time frame: Up to 12 months
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.
Time frame: 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.
Time frame: Up to 12 months
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Yale Cancer Center
New Haven, Connecticut, United States
COMPLETEDMount Sinai Medical Center Comprehensive Cancer Center
Miami Beach, Florida, United States
RECRUITINGEmory University
Atlanta, Georgia, United States
RECRUITINGUniversity of Kansas Cancer Center
Westwood, Kansas, United States
WITHDRAWNHackensack University Medical Center
Hackensack, New Jersey, United States
NOT_YET_RECRUITINGMemorial Sloan Kettering Cancer Center
New York, New York, United States
COMPLETED...and 36 more locations