This is an open-label, nonrandomized, multicenter, dose escalation, and dose expansion first-in human (FIH) Phase 1 study to determine the safety, tolerability, PK, pharmacodynamics, and preliminary efficacy of INCA00186 when given alone or in combination with INCB106385 and/or retifanlimab in participants with specific advanced solid tumors; squamous cell carcinoma of the head and neck (SCCHN) and specified gastrointestinal (GI) malignancies have been selected as indications of interest for this study. Participants with CD8 T-cell-positive tumors will be selected as these tumors are more likely to respond to immunotherapy.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
57
INCA00186 will be administered every 2 weeks or 4 weeks as per protocol
Retifanlimab will be administered every 4 weeks as per protocol
INCB106385 will be administered orally once or twice a day.
The Angeles Clinic and Research Institute
Los Angeles, California, United States
Emory University
Atlanta, Georgia, United States
University of Maryland-Greenebaum Cancer Center
Baltimore, Maryland, United States
Hackensack University Medical Center
Hackensack, New Jersey, United States
Carolina Bio-Oncology Institute, Pllc
Huntersville, North Carolina, United States
Evaluation of the safety and tolerability of INCA00186 as monotherapy and in combination with retifanlimab and/or INCB106385 as measured by the number of participants with adverse eventsductions and withdrawal of treatment due to AEs
Time frame: 90 days after study completion totaling up to 27 months
Evaluation of Dose-Limiting Toxicity (DLTs) of INCA00186 as monotherapy and in combination with retifanlimab and/or INCB106385 as measured by safety events during treatment
Time frame: 90 days after study completion totaling up to 27 months
Evaluation of Recommended Dose for Expansion (RDE) of INCA00186 as monotherapy and in combination with retifanlimab and/or INCB106385 as measured by safety, PK and PD data
Time frame: 90 days after study completion totaling up to 27 months
Determination of PK parameter Maximum Observed Plasma Concentration (Cmax) for INCA00186
Time frame: Cycle 1 days 1, 2, 8, 15, 22; Cycle 2 days 1, 8; Day 1 of every other cycle starting at Cycle 4 (ie, Cycle 4 day 1, Cycle 6 day 1, etc; each cycle is 28 days) + 30 day follow-up; approximately 24 months
Determination of PK parameter of Time to Maximum Plasma Concentration (tmax) for INCA00186
Time frame: Cycle 1 days 1, 2, 8, 15, 22; Cycle 2 days 1, 8; Day 1 of every other cycle starting at Cycle 4 (ie, Cycle 4 day 1, Cycle 6 day 1, etc; each cycle is 28 days) + 30 day follow-up; approximately 24 months
Determination of PK parameter of concentration at the end of the dosing interval (Ctau) for INCA00186
Time frame: Cycle 1 days 1, 2, 8, 15, 22; Cycle 2 days 1, 8; Day 1 of every other cycle starting at Cycle 4 (ie, Cycle 4 day 1, Cycle 6 day 1, etc; each cycle is 28 days) + 30 day follow-up; approximately 24 months
Determination of PK parameter of area under the plasma or serum concentration-time curve (AUC) for INCA00186
Time frame: Cycle 1 days 1, 2, 8, 15, 22; Cycle 2 days 1, 8; Day 1 of every other cycle starting at Cycle 4 (ie, Cycle 4 day 1, Cycle 6 day 1, etc; each cycle is 28 days) + 30 day follow-up; approximately 24 months
Determination of PK parameter of total clearance (CL) for INCA00186
Time frame: Cycle 1 days 1, 2, 8, 15, 22; Cycle 2 days 1, 8; Day 1 of every other cycle starting at Cycle 4 (ie, Cycle 4 day 1, Cycle 6 day 1, etc; each cycle is 28 days) + 30 day follow-up; approximately 24 months
Determination of PK parameter of volume of distribution (Vz) for INCA00186
Time frame: Cycle 1 days 1, 2, 8, 15, 22; Cycle 2 days 1, 8; Day 1 of every other cycle starting at Cycle 4 (ie, Cycle 4 day 1, Cycle 6 day 1, etc; each cycle is 28 days) + 30 day follow-up; approximately 24 months
Determination of PK parameter half-life (t1/2) for INCA00186
Time frame: Cycle 1 days 1, 2, 8, 15, 22; Cycle 2 days 1, 8; Day 1 of every other cycle starting at Cycle 4 (ie, Cycle 4 day 1, Cycle 6 day 1, etc; each cycle is 28 days) + 30 day follow-up; approximately 24 months
Intratumoral effect of INCA0186 on CD73 enzymatic activity
Time frame: 2 biopsy samples will be taken: pre-treatment and on-treatment on Cycle 1 Day 22 (for every 2 week INCA00186 dosing group) or Cycle 2 Day 8 (for every 4 week INCA00186 dosing group); each cycle is 28 days; sampling will be taken within 2 months.
Objective Response Rate (ORR) by radiographic disease assessment
Time frame: Baseline through end of study up, to 24 months
Disease Control Response (DCR) determined by radiographic disease assessment
Time frame: Baseline through end of study, up to 24 months
Duration of Response (DOR) from earliest date of disease response until earliest date of disease progression as determined by radiographic disease assessment, or death if occurring sooner than progression
Time frame: Baseline through end of study, up to 24 months
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Vanderbilt Medical Center
Nashville, Tennessee, United States
Md Anderson Cancer Center
Houston, Texas, United States
South Texas Accelerated Research Therapeutics
San Antonio, Texas, United States
Innsbruck University Hospital
Innsbruck, Austria
Landeskrankenhaus Salzburg
Salzburg, Austria
...and 22 more locations