Advanced/Metastatic, Head and Neck Cancer, Stomach or Esophageal Cancer
Study of INCA 0186 in Subjects with Advanced Solid Tumors
Clinical Study Purpose
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.
Clinical Study Summary
Clinical Study Locations
Key Inclusion and Exclusion Criteria
Inclusion Criteria
- Ability to comprehend and willingness to sign a written ICF for the study.
- Male or female participant aged 18 years or older inclusive at the time of signing the ICF.
Exclusion Criteria
- Clinically significant cardiac disease, unstable angina, acute myocardial infarction within
- 6 months of Cycle 1 Day 1, and New York Heart Association Class III or IV congestive
Protocol Summary
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
Timeframe: 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
Timeframe: 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
Timeframe: 90 days after study completion totaling up to 27 months
Determination of PK parameter Maximum Observed Plasma Concentration (Cmax) for INCA00186
Timeframe: 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
Timeframe: 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
Timeframe: 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
Timeframe: 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
Timeframe: 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
Timeframe: 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
Timeframe: 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
Timeframe: 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
Timeframe: Baseline through end of study up, to 24 months
Disease Control Response (DCR) determined by radiographic disease assessment
Timeframe: 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
Timeframe: Baseline through end of study, up to 24 months