This is a Phase 1/2, multi-center, open-label basket study designed to evaluate the safety and anti-tumor activity of IDE196 in patients with solid tumors harboring GNAQ or GNA11 (GNAQ/11) mutations or PRKC fusions, including metastatic uveal melanoma (MUM), cutaneous melanoma, colorectal cancer, and other solid tumors. Phase 1 (dose escalation - monotherapy) will assess safety, tolerability and pharmacokinetics of IDE196 via standard dose escalation scheme and determine the recommended Phase 2 dose. Safety and anti-tumor activity will be assessed in the Phase 2 (dose expansion) part of the study. Phase 1 (dose escalation - binimetib combination) will assess safety, tolerability and pharmacokinetics of IDE196 and binimetinib via standard dose escalation scheme and determine the recommended Phase 2 dose. Safety and anti-tumor activity will be assessed in the Phase 2 (dose expansion) part of the study. Phase 1 (dose escalation - crizotinib combination) will assess safety, tolerability and pharmacokinetics of IDE196 and crizotinib via standard dose escalation scheme and determine the recommended Phase 2 dose. Safety and anti-tumor activity will be assessed in the Phase 2 (dose expansion) part of the study. Evaluation of safety and efficacy across multiple doses may be explored in the dose optimization part of the study. Crizotinib monotherapy with crossover to combination cohort may be assessed for safety and to show the contribution of each study drug to anti-tumor activity. As of Protocol Amendment 10, Phase 1, Phase 2 dose expansion in IDE196 monotherapy, and Phase 2 dose expansion of IDE196 in combination with binimetinib have been fully enrolled. There were no patients enrolled in the crizotinib monotherapy cohorts.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
336
IDE196 dosed orally, twice daily for each 28-day cycle
Binimetinib dosed orally, twice daily for each 28-day cycle
Crizotinib dosed orally, twice daily for each 28-day cycle
UCLA Medical Center
Los Angeles, California, United States
RECRUITINGSan Francisco Oncology Associates
San Francisco, California, United States
ACTIVE_NOT_RECRUITINGSCRI - Denver
Denver, Colorado, United States
RECRUITINGUniversity of Iowa
Iowa City, Iowa, United States
ACTIVE_NOT_RECRUITINGCancer Hematology Centers Western Michigan
Grand Rapids, Michigan, United States
ACTIVE_NOT_RECRUITINGColumbia University Medical Center - Herbert Irving Pavilion
New York, New York, United States
ACTIVE_NOT_RECRUITINGDuke University Medical Center
Durham, North Carolina, United States
RECRUITINGUniversity of Cincinnati Cancer Center
Cincinnati, Ohio, United States
RECRUITINGThe Cleveland Clinic Foundation
Cleveland, Ohio, United States
ACTIVE_NOT_RECRUITINGSidney Kimmel Cancer Center at Thomas Jefferson University
Philadelphia, Pennsylvania, United States
RECRUITING...and 5 more locations
Dose-limiting Toxicity (DLT)
Determine DLT of IDE196 as monotherapy, in combination with Binimetinib, or in combination with Crizotinib
Time frame: 28 days following first dose of IDE196 as monotherapy, in combination with Binimetinib, or in combination with Crizotinib
Maximum Tolerated Dose (MTD)
Determine MTD of IDE196 as monotherapy, in combination with Binimetinib, or in combination with Crizotinib
Time frame: 28 days following first dose of IDE196 as monotherapy, in combination with Binimetinib, or in combination with Crizotinib
Recommended Phase 2 Dose (RP2D) as monotherapy, in combination with Binimetinib, or in combination with Crizotinib
Determine RP2D of IDE196 as monotherapy, in combination with Binimetinib, or in combination with Crizotinib
Time frame: Approx. 6 months
Incidence of Adverse Events
Safety and tolerability of IDE196 either as monotherapy, in combination with Binimetinib, or in combination with Crizotinib
Time frame: Approx. 8 months
Plasma Concentrations of IDE196 as monotherapy, in combination with Binimetinib, or in combination with Crizotinib
Pharmacokinetics of IDE196 as monotherapy, in combination with Binimetinib, or in combination with Crizotinib
Time frame: Approx. 6 months
Plasma Concentrations of Crizotinib administered in combination with IDE196
Pharmacokinetics of Crizotinib in combination with IDE196
Time frame: Approx. 6 months
Plasma Concentrations of Binimetinib administered in combination with IDE196
Pharmacokinetics of Binimetinib in combination with IDE196
Time frame: Approx. 6 months
Overall Response Rate (ORR) of IDE196 monotherapy, in combination with Binimetinib, and in combination with Crizotinib in Dose Expansion cohorts by Investigator response assessment
Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (v1.1) criteria
Time frame: Approx. 8 months
Duration of Response (DOR) of IDE196 monotherapy, in combination with Binimetinib, and in combination with Crizotinib in Dose Expansion cohorts by Investigator response assessment
RECIST v1.1
Time frame: Approx. 8 months
Phramacokinetic parameters of bupropion, hydroxybupropion, repaglinide, flurbiprofen, omeprazole, midazolam, total dabigatran, and the exposures of pyridoxic acid by IDE196 monotherapy and IDE196 in combination with Crizotinib
PK parameters of drug cocktail
Time frame: Approx. 8 months
Progression Free Survival (PFS) of IDE196 monotherapy, in combination with Binimetinib, and in combination with Crizotinib in Dose Expansion cohorts by Investigator response assessment
RECIST v1.1
Time frame: Approx. 18 months
Overall Response Rate (ORR) of IDE196 monotherapy, in combination with Binimetinib, and in combination with Crizotinib in Dose Expansion cohorts and by prior treatment status (pretreated or treatment naive) by Investigator response assessment
Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (v1.1) criteria
Time frame: Approx. 18 months
Duration of Response (DOR) of IDE196 monotherapy, in combination with Binimetinib, and in combination with Crizotinib in Dose Expansion cohorts by prior treatment status (pretreated or treatment naive) by Investigator response assessment
RECIST v1.1
Time frame: Approx. 18 months
Disease Control Rate (DCR) by Investigator
RECIST v1.1
Time frame: Approx. 18 months
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