Study of IDE196 in Patients With Solid Tumors Harboring GNAQ/11 Mutations or PRKC Fusions

• Status: Recruiting
• Trial end date: 2023-04-30
• Target enrollment: 0
• Participant gender: All

Summary

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.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: IDEAYA Biosciences
• Treatments: Crizotinib

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