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

Ideaya Biosciences

Status and phase: Enrolling; Phase 2; Phase 1

Conditions: Other Solid Tumors; Metastatic Uveal Melanoma; Colorectal Cancer; Cutaneous Melanoma

Treatments: Drug: IDE196; Drug: Binimetinib; Drug: Crizotinib

Study type: Interventional

Funder types: Industry

Identifiers

NCT03947385

IDE196-001

Details and patient eligibility

About

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. 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.

Enrollment: 278 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

• Known symptomatic brain metastases
• 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
• Known acquired immunodeficiency syndrome (AIDS)-related illness, hepatitis B virus, or hepatitis C virus
• Active infection requiring ongoing therapy
• Recent surgery or radiotherapy
• Prior gastrectomy or upper bowel removal or any other gastrointestinal disorder or defect
• Females who are pregnant or breastfeeding
• Impaired cardiac function
• Treatment with prohibited medications that cannot be discontinued prior to study entry
• For patients receiving IDE196 powder-in-capsule (PIC) formulation or crizotinib, allergy to mammalian meat products and gelatin

Binimetinib Combination Additional Exclusion Criteria

• Prior treatment with a MEK inhibitor
• History or current evidence of retinal vein occlusion (RVO) or current risk factors for RVO
• History of interstitial lung disease
• History of thromboembolic or cerebrovascular events ≤ 12 weeks prior to first dose
• Concurrent neuromuscular disorders that are associated with elevated creatine phosphokinase (CPK)
• Uncontrolled arterial hypertension despite medical treatment
• Allergy to binimetinib or its components
• History of syncope

Crizotinib Combination Additional Exclusion Criteria:

• Prior therapy directly targeting ALK, MET, or ROS1
• Spinal cord compression
• History of pneumonitis or interstitial lung disease
• History of syncope

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

---

278 participants in 9 patient groups

Dose Escalation Monotherapy

Experimental group

Description:

IDE196 dosed orally, twice daily (BID) for each 28-day cycle

Treatment:

Drug: IDE196

Dose Expansion Monotherapy

Experimental group

Description:

RP2D in MUM and non-MUM tumors harboring GNAQ/11 mutations or PRKC fusions (cutaneous melanoma, CRC, other solid tumors)

Treatment:

Drug: IDE196

Dose Escalation Binimetinib Combination

Experimental group

Description:

IDE196 dosed orally, twice daily (BID) for each 28-day cycle and Binimetinib dosed orally, twice daily (BID) for each 28-day cycle

Treatment:

Drug: Binimetinib

Drug: IDE196

Dose Expansion Binimetinib Combination

Experimental group

Description:

RP2D in MUM and non-MUM tumors harboring GNAQ/11 mutations (cutaneous melanoma, CRC, other solid tumors)

Treatment:

Drug: Binimetinib

Drug: IDE196

Dose Escalation Crizotinib Combination

Experimental group

Description:

IDE196 dosed orally, twice daily (BID) for each 28-day cycle and Crizotinib dosed orally, twice daily (BID) for each 28-day cycle

Treatment:

Drug: Crizotinib

Drug: IDE196

Dose Expansion Crizotinib Combination

Experimental group

Description:

RP2D in MUM and non-MUM tumors harboring GNAQ/11 mutations (cutaneous melanoma, CRC, other solid tumors)

Treatment:

Drug: Crizotinib

Drug: IDE196

Dose Optimization Crizotinib Combination

Experimental group

Description:

IDE196 dosed orally, twice daily (BID) for each 28-day cycle and Crizotinib dosed orally, twice daily (BID) for each 28-day cycle

Treatment:

Drug: Crizotinib

Drug: IDE196

Crizotinib Monotherapy with Crossover to Combination

Experimental group

Description:

Crizotinib dosed orally, twice daily (BID) for each 28-day cycle until disease progression then IDE196 added and dosed orally, twice daily (BID) for each 28-day cycle

Treatment:

Drug: Crizotinib

Drug: IDE196

Tablet PK Substudy

Experimental group

Description:

IDE196 dosed orally, once on Cycle 1 Day 1; thereafter, twice daily (BID) for each 28-day cycle

Treatment:

Drug: IDE196