Evaluating IDE196 for patients with specific solid tumors

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

This study is testing a new treatment called IDE196 for people with specific solid tumors that have certain genetic changes to see if it can help shrink their tumors and how safe it is.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 336 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: IDEAYA Biosciences (Industry-sponsored)
• Drugs / interventions: Crizotinib, chemotherapy, binimetinib
• Locations: 15 sites (Los Angeles, California and 14 other locations)
• Trial ID: NCT03947385 on ClinicalTrials.gov

What this trial studies

This Phase 1/2 multi-center, open-label basket study aims to assess the safety and anti-tumor activity of IDE196 in patients with solid tumors that have GNAQ or GNA11 mutations or PRKC fusions. The study consists of a dose escalation phase to determine the recommended dose and a dose expansion phase to evaluate the treatment's efficacy. Patients will receive IDE196 alone or in combination with binimetinib or crizotinib, with safety and pharmacokinetics being closely monitored throughout the trial.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and older with metastatic uveal melanoma, cutaneous melanoma, colorectal cancer, or other solid tumors harboring GNAQ/11 mutations or PRKC fusions.

Not a fit: Patients without GNAQ/11 mutations or PRKC fusions, or those who have already received certain prior therapies may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with specific genetic mutations in their tumors.

How similar studies have performed: Other studies targeting similar genetic mutations have shown promise, indicating potential for success in this approach.

Eligibility criteria

Inclusion Criteria:

* Patient must be ≥18 years of age and able to provide written informed consent
* Diagnosis of the following:

  o MUM: Uveal melanoma with histological or cytological confirmed metastatic disease. Metastatic disease may be treatment naïve or have progressed on or after most recent therapy. If the most recent therapy was an immune-oncology agent, PD must be confirmed.

  \- If a patient is treatment naïve and human leukocyte antigen (HLA)-A\*02:01 positive\*\*\*, documentation is required to provide rationale why treatment with tebentafusp is not the ideal firstline treatment approach or of the patient's intolerance to tebentafusp.

  \*\*\*To be enrolled in the HLA-A\*02:01 positive cohort, HLA status must be documented by test results from a CAP/CLIA-certified laboratory.
* Measurable disease per RECIST v1.1
* 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

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 Biopsy-eligible patients
* Accessible lesion(s) that permit a total of at least two biopsies without unacceptable risk of a significant procedural complication.

Exclusion Criteria:

* Previous treatment with a PKC inhibitor
* Known MSI-H/dMMR tumors who have not previously received immune checkpoint inhibitors
* Known symptomatic brain metastases
* 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

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
* History of thromboembolic or cerebrovascular events ≤12 weeks prior to first dose of study treatment

PK Substudy (optional) with Pravastatin Additional Exclusion Criteria:

* Taken any dose of statin or inhibitor of organic anion transporting polypeptide within 7 days prior to enrollment in the study and cannot refrain from them through C2D1
* Taken drugs that interfere with the absorption, metabolism, or elimination of pravastatin
* Any contraindication associated to the use of statins or hypersensitivity component of pravastatin
* Active liver disease

DDI Cocktail Substudy Additional Exclusion Criteria:

* Treatment with bupropion, repaglinide, flurbiprofen, omeprazole, esomeprazole, midazolam, and dabigatran etexilate within 7 days prior to Cycle 1 Day -1.
* Intake of vitamin supplements containing Vitamin B6 (pyridoxine), grapefruit/grapefruit juice, or Seville orange juice within 7 days prior to Cycle 1 Day -1.
* Intake of any strong or moderate inhibitor of CYP2B6, CYP2CI, CYP2C9, CYP2C10 and OAT3 is prohibited within 7 days or within 5 half-lives, whichever is longer, of Cycle 1 Day -1.
* Moderate and strong inhibitors of CYP2A4/5 or P-gp are prohibited within 7 days, or within 5 half-lives, whichever is longer, of Cycle 1 Day -1.
* Intake of strong or moderate inducers of CYP3A4/5, CYP2B6, CYP2C9, CYP2C19, or OAT3 is prohibited during 15 days, or 5 half-lives, whichever is longer, prior to Cycle 1 Day -1.

Where this trial is running

Los Angeles, California and 14 other locations

• UCLA Medical Center — Los Angeles, California, United States (Recruiting)
• San Francisco Oncology Associates — San Francisco, California, United States (Active_not_recruiting)
• SCRI - Denver — Denver, Colorado, United States (Recruiting)
• University of Iowa — Iowa City, Iowa, United States (Active_not_recruiting)
• Cancer Hematology Centers Western Michigan — Grand Rapids, Michigan, United States (Active_not_recruiting)
• Columbia University Medical Center - Herbert Irving Pavilion — New York, New York, United States (Active_not_recruiting)
• Duke University Medical Center — Durham, North Carolina, United States (Recruiting)
• University of Cincinnati Cancer Center — Cincinnati, Ohio, United States (Recruiting)
• The Cleveland Clinic Foundation — Cleveland, Ohio, United States (Active_not_recruiting)
• Sidney Kimmel Cancer Center at Thomas Jefferson University — Philadelphia, Pennsylvania, United States (Recruiting)
• The Sarah Cannon Research Institute/Tennessee Oncology — Nashville, Tennessee, United States (Recruiting)
• The University of Texas MD Anderson Cancer Center — Houston, Texas, United States (Recruiting)
• Westmead Hospital — Sydney, New South Wales, Australia (Active_not_recruiting)
• Queensland — Woolloongabba, Australia (Active_not_recruiting)
• Princess Margaret Cancer Centre — Toronto, Ontario, Canada (Active_not_recruiting)

Study contacts

• Study coordinator: IDEAYA Clinical Trials

Conditions Metastatic Uveal Melanoma; Cutaneous Melanoma; Colorectal Cancer; Other Solid Tumors; Uveal Melanoma; Protein Kinase C; Ophthalmology; Ocular Oncology