Description:
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 Tablet and Food Effect Pharmacokinetic (PK) Substudy will assess the PK profile of
IDE196 tablet and evaluate the effects of food on the PK profile of IDE196 tablet
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.
Title
- Brief Title: Study of IDE196 in Patients With Solid Tumors Harboring GNAQ/11 Mutations or PRKC Fusions
- Official Title: A Phase 1/2 Study of IDE196 in Patients With Solid Tumors Harboring GNAQ/11 Mutations or PRKC Fusions
Clinical Trial IDs
- ORG STUDY ID:
IDE196-001
- NCT ID:
NCT03947385
Conditions
- Metastatic Uveal Melanoma
- Cutaneous Melanoma
- Colorectal Cancer
- Other Solid Tumors
Interventions
Drug | Synonyms | Arms |
---|
IDE196 | Protein Kinase C (PKC) Inhibitor | Dose Escalation Binimetinib Combination |
Binimetinib | MEKTOVI | Dose Escalation Binimetinib Combination |
Crizotinib | XALKORI | Dose Escalation Crizotinib Combination |
Purpose
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 Tablet and Food Effect Pharmacokinetic (PK) Substudy will assess the PK profile of
IDE196 tablet and evaluate the effects of food on the PK profile of IDE196 tablet
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.
Trial Arms
Name | Type | Description | Interventions |
---|
Dose Escalation Monotherapy | Experimental | IDE196 dosed orally, twice daily (BID) for each 28-day cycle | |
Dose Expansion Monotherapy | Experimental | RP2D in MUM and non-MUM tumors harboring GNAQ/11 mutations or PRKC fusions (cutaneous melanoma, CRC, other solid tumors) | |
Dose Escalation Binimetinib Combination | Experimental | IDE196 dosed orally, twice daily (BID) for each 28-day cycle and Binimetinib dosed orally, twice daily (BID) for each 28-day cycle | |
Dose Expansion Binimetinib Combination | Experimental | RP2D in MUM and non-MUM tumors harboring GNAQ/11 mutations (cutaneous melanoma, CRC, other solid tumors) | |
Dose Escalation Crizotinib Combination | Experimental | IDE196 dosed orally, twice daily (BID) for each 28-day cycle and Crizotinib dosed orally, twice daily (BID) for each 28-day cycle | |
Dose Expansion Crizotinib Combination | Experimental | RP2D in MUM and non-MUM tumors harboring GNAQ/11 mutations (cutaneous melanoma, CRC, other solid tumors) | |
Tablet PK Substudy | Experimental | IDE196 dosed orally, once on Cycle 1 Day 1; thereafter, twice daily (BID) for each 28-day cycle | |
Eligibility Criteria
Inclusion Criteria:
- Patient must be ≥18 years of age
- Diagnosis of one of the following:
- MUM: Uveal melanoma with histological or cytological confirmed metastatic
disease. Or
- Non-MUM: Advanced cutaneous melanoma, colorectal cancer, or other solid tumor
that has progressed following prior standard therapies or that has no
satisfactory alternative therapies and has evidence of GNAQ/11 hotspot mutation
- Measurable disease
- Eastern Cooperative Oncology Group ≤1 and expected life expectancy of > 3 months
- Adequate organ function at screening
- Adequate contraceptive measures for non-sterilized male and female patients of
childbearing potential
Binimetinib Combination Additional Inclusion Criteria:
• Adequate cardiac function represented by left ventricular ejection fraction (LVEF) ≥ 50%
Crizotinib Combination Additional Inclusion Criteria:
- Prior chemotherapy other therapies as applicable or major surgeries must have been
completed at least 4 weeks prior to initiation of crizotinib
- Patients with preexisting peripheral neuropathy can be included if it is Grade 1 or
lower, prior to initiation of crizotinib
Exclusion Criteria:
- Another malignancy
- Previous treatment with a PKC inhibitor
- Known MSI-H/dMMR tumors who have not previously received immune checkpoint inhibitors
- Adverse events from prior anti-cancer therapy that have not resolved
- Untreated or symptomatic central nervous system metastases
- Human immunodeficiency virus, acquired immunodeficiency syndrome related illness,
hepatitis B virus, or hepatitis C virus
- Recent surgery or radiotherapy
- Females who are pregnant or breastfeeding
- Impaired cardiac function
- For patients receiving IDE196 powder-in-capsule (PIC) formulation or crizotinib,
allergy to mammalian meat products and gelatin
Binimetinib Combination Additional Exclusion Criteria
- Patient has received prior treatment with a MEK inhibitor
- History of interstitial lung disease
- History of thromboembolic or cerebrovascular events ≤ 12 weeks prior to first dose
- History or current evidence of central serous retinopathy (CSR) or retinal vein
occlusion (RVO); History of retinal degenerative disease
- Concurrent neuromuscular disorders that are associated with elevated creatine
phosphokinase (CPK)
- Uncontrolled arterial hypertension despite medical treatment
- Allergy to binimetinib or its components
Crizotinib Combination Additional Exclusion Criteria:
- Prior therapy directly targeting ALK, MET, or ROS1
- Spinal cord compression
- Carcinomatous meningitis or leptomeningeal disease
- History of pneumonitis or interstitial lung disease
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Dose-limiting Toxicity (DLT) |
Time Frame: | 28 days following first dose of IDE196 as monotherapy, in combination with Binimetinib, or in combination with Crizotinib |
Safety Issue: | |
Description: | Determine DLT of IDE196 as monotherapy, in combination with Binimetinib, or in combination with Crizotinib |
Secondary Outcome Measures
Measure: | Overall Response Rate (ORR) in Dose Expansion by Blinded Independent Review Committee |
Time Frame: | Approx. 30 months |
Safety Issue: | |
Description: | Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (v1.1) criteria |
Measure: | Duration of Response by Blinded Independent Review Committee |
Time Frame: | Approx. 30 months |
Safety Issue: | |
Description: | RECIST v1.1 |
Measure: | ORR by Investigator |
Time Frame: | Approx. 30 months |
Safety Issue: | |
Description: | RECIST v1.1 |
Measure: | Duration of Response by Investigator |
Time Frame: | Approx. 30 months |
Safety Issue: | |
Description: | RECIST v1.1 |
Measure: | Disease Control by Investigator |
Time Frame: | Approx. 30 months |
Safety Issue: | |
Description: | RECIST v1.1 |
Measure: | Numbers of Participants with Adverse Events |
Time Frame: | Approx. 30 months |
Safety Issue: | |
Description: | Safety and tolerability of IDE196 either as monotherapy, in combination with Binimetinib, or in combination with Crizotinib |
Details
Phase: | Phase 1/Phase 2 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | IDEAYA Biosciences |
Last Updated
February 17, 2021