RecruitingPhase 1 / Phase 2

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

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

Who can join

As published by the study on ClinicalTrials.gov. "Not stated" means the study hasn't said — ask the study team.

Age
18 Years and older
Sex
All sexes
Healthy volunteers
Not accepted
Compensation
Not stated

Other requirements are listed under Eligibility below. Only the study team can confirm whether you can join.

What to expect

No one can promise a trial will help you personally — that is what the research is trying to find out.

What participation involves

Not stated in the study description — ask the study team about visits and procedures.

Compensation
Not stated
  • Study-related exams and procedures are typically provided at no cost. This is how many trials work in general — confirm the details for this study with the study team.
  • Participants are monitored closely by the research team throughout the study.
  • Some participants may receive access to an investigational treatment, which is still being studied.
  • Your participation helps researchers learn whether this approach could help future patients.

About this study

In plain language

This study tests the safety of IDE196 and how well it fights cancer, alone or with binimetinib or crizotinib. It studies adults with solid tumors that have certain gene changes, including eye melanoma that has spread. Some parts of the study are already fully enrolled.

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 (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. As of Protocol Amendment 10, Phase 1, Phase 2 dose expansion in IDE196 monotherapy, and Phase 2 dose expansion of IDE196 in combination with binimetinib have been fully enrolled. There were no patients enrolled in the crizotinib monotherapy cohorts.

Compensation is read from the study's own description and may be missing — always confirm with the study team.

Eligibility

Who can join

  • Be age 18 or older and able to give written consent.
  • Have uveal melanoma (a cancer that starts in the eye) that has spread, confirmed by testing cells or tissue. It may be untreated or have worsened during or after the latest treatment.
  • If your latest treatment used your immune system to fight cancer, tests must confirm that the cancer worsened.
  • If untreated and positive for HLA-A*02:01, a genetic marker, have a written reason why tebentafusp is not a good first treatment or cannot be tolerated. The marker-specific group requires results from a certified lab.
  • Have cancer that can be measured, be able to do most daily activities, and be expected to live more than 3 months.
  • Have organs that work well enough. Use suitable birth control if you or your partner could become pregnant.
  • For the crizotinib combination: finish prior chemotherapy, other treatments as required, or major surgery at least 4 weeks before starting. Any existing nerve damage must be mild.
  • For patients having biopsies: have a tumor area that allows at least two tissue samples to be taken without an unacceptable risk of serious harm.

Who can't join

  • Prior treatment with a PKC inhibitor, a type of cancer drug; or an MSI-H/dMMR tumor (certain DNA repair changes) without prior immune checkpoint treatment.
  • Cancer that has spread to the brain and causes symptoms, or side effects from earlier cancer treatment that have not gone away.
  • An AIDS-related illness, hepatitis B or C, or an active infection needing ongoing treatment.
  • Recent surgery or radiation; past removal of the stomach or upper bowel; or another stomach or bowel disorder or defect.
  • Pregnancy, breastfeeding, heart problems, or use of banned medicines that cannot be stopped. Certain IDE196 capsules and crizotinib also rule out people allergic to mammal meat products and gelatin.
  • For the crizotinib combination: prior drugs targeting ALK, MET, or ROS1; pressure on the spinal cord; past lung inflammation or scarring; past fainting; or a blood clot or stroke-related event within 12 weeks.
  • For the optional pravastatin study: certain recent medicines that cannot be avoided, medicines that affect pravastatin, reasons statins are unsafe, allergy to pravastatin ingredients, or active liver disease.
  • For the drug-interaction study: certain recent medicines or supplements, including vitamin B6, or recent grapefruit, grapefruit juice, or Seville orange juice. Required waiting times depend on the product.

Simplified for readability. The official criteria below are what the study team uses.

Official 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.

Study sites (12)

CA

CO

IA

MI

NC

NY

OH

PA

TN

  • The Sarah Cannon Research Institute/Tennessee Oncology · Nashville, TN 37203askSARAH · Study contact · 844-482-4812Meredith McKean, MD · Principal investigatorMore trials in Nashville

TX