Summary

Eligibility
for people ages 18 years and up (full criteria)
Location
at UCLA
Dates
study started
completion around
Principal Investigator
by Bartosz Chmielowski (ucla)

Description

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. 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.

Official Title

A Phase 1/2 Study of IDE196 in Patients With Solid Tumors Harboring GNAQ/11 Mutations or PRKC Fusions

Keywords

Metastatic Uveal Melanoma, Cutaneous Melanoma, Colorectal Cancer, Other Solid Tumors, Uveal Melanoma, Protein Kinase C, Ophthalmology, Ocular Oncology, Darovasertib, IDE196, Ocular Melanoma, Melanoma, Crizotinib, Binimetinib, Tablet PK Substudy

Eligibility

You can join if…

Open to people ages 18 years and up

  • 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

You CAN'T join if...

  • 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

Locations

  • UCLA Medical Center accepting new patients
    Los Angeles California 90095 United States
  • San Francisco Oncology Associates accepting new patients
    San Francisco California 94115 United States

Lead Scientist at University of California Health

  • Bartosz Chmielowski (ucla)
    HS Clinical Professor, Medicine. Authored (or co-authored) 128 research publications

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
IDEAYA Biosciences
ID
NCT03947385
Phase
Phase 1/2 research study
Study Type
Interventional
Participants
Expecting 278 study participants
Last Updated