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

NCT03947385 | Recruiting Phase 1 FDA Drug

• 1 other identifier: IDE196-001
• Study Type: interventional
• Target: 336
• Locations: 3 countries
• Sites: 15

Brief 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 (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.

Conditions

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

Keywords

Metastatic Uveal Melanoma; Uveal Melanoma; Protein Kinase C; Ophthalmology; Ocular Oncology; Darovasertib; IDE196; Ocular Melanoma

Outcome Measures

Primary Outcomes (10)

• Dose-limiting Toxicity (DLT)

  Determine DLT of IDE196 as monotherapy, in combination with Binimetinib, or in combination with Crizotinib

  28 days following first dose of IDE196 as monotherapy, in combination with Binimetinib, or in combination with Crizotinib

• Maximum Tolerated Dose (MTD)

  Determine MTD of IDE196 as monotherapy, in combination with Binimetinib, or in combination with Crizotinib

  28 days following first dose of IDE196 as monotherapy, in combination with Binimetinib, or in combination with Crizotinib

• Recommended Phase 2 Dose (RP2D) as monotherapy, in combination with Binimetinib, or in combination with Crizotinib

  Determine RP2D of IDE196 as monotherapy, in combination with Binimetinib, or in combination with Crizotinib

  Approx. 6 months

• Incidence of Adverse Events

  Safety and tolerability of IDE196 either as monotherapy, in combination with Binimetinib, or in combination with Crizotinib

  Approx. 8 months

• Plasma Concentrations of IDE196 as monotherapy, in combination with Binimetinib, or in combination with Crizotinib

  Pharmacokinetics of IDE196 as monotherapy, in combination with Binimetinib, or in combination with Crizotinib

  Approx. 6 months

• Plasma Concentrations of Crizotinib administered in combination with IDE196

  Pharmacokinetics of Crizotinib in combination with IDE196

  Approx. 6 months

• Plasma Concentrations of Binimetinib administered in combination with IDE196

  Pharmacokinetics of Binimetinib in combination with IDE196

  Approx. 6 months

• Overall Response Rate (ORR) of IDE196 monotherapy, in combination with Binimetinib, and in combination with Crizotinib in Dose Expansion cohorts by Investigator response assessment

  Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (v1.1) criteria

  Approx. 8 months

• Duration of Response (DOR) of IDE196 monotherapy, in combination with Binimetinib, and in combination with Crizotinib in Dose Expansion cohorts by Investigator response assessment

  RECIST v1.1

  Approx. 8 months

• Phramacokinetic parameters of bupropion, hydroxybupropion, repaglinide, flurbiprofen, omeprazole, midazolam, total dabigatran, and the exposures of pyridoxic acid by IDE196 monotherapy and IDE196 in combination with Crizotinib

  PK parameters of drug cocktail

  Approx. 8 months

Secondary Outcomes (4)

• Progression Free Survival (PFS) of IDE196 monotherapy, in combination with Binimetinib, and in combination with Crizotinib in Dose Expansion cohorts by Investigator response assessment

  Approx. 18 months

• Overall Response Rate (ORR) of IDE196 monotherapy, in combination with Binimetinib, and in combination with Crizotinib in Dose Expansion cohorts and by prior treatment status (pretreated or treatment naive) by Investigator response assessment

  Approx. 18 months

• Duration of Response (DOR) of IDE196 monotherapy, in combination with Binimetinib, and in combination with Crizotinib in Dose Expansion cohorts by prior treatment status (pretreated or treatment naive) by Investigator response assessment

  Approx. 18 months

• Disease Control Rate (DCR) by Investigator

  Approx. 18 months

Other Outcomes (9)

• Overall Survival

  Approx. 18 months

• Anti-tumor activity (ORR/DOR/PFS) of IDE196 monotherapy, in combination with Binimetinib, and in combination with Crizotinib in Dose Expansion cohorts by Blinded Independent Review Committee (BICR)

  Approx. 18 months

• Anti-tumor activity (ORR/DOR/DCR) of IDE196 monotherapy, in combination with Binimetinib, and in combination with Crizotinib in phase 1 Dose Escalation cohorts by Investigator response assessment

  Approx. 18 months

Study Arms (8)

Dose Escalation Monotherapy (Enrollment Complete)

EXPERIMENTAL

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

Drug: IDE196

Dose Expansion Monotherapy (Enrollment Complete)

EXPERIMENTAL

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

Drug: IDE196

Dose Escalation Binimetinib Combination (Enrollment Complete)

EXPERIMENTAL

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

Drug: IDE196; Drug: Binimetinib

Dose Expansion Binimetinib Combination (Enrollment Complete)

EXPERIMENTAL

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

Drug: IDE196; Drug: Binimetinib

Dose Escalation Crizotinib Combination (Enrollment Complete)

EXPERIMENTAL

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

Drug: IDE196; Drug: Crizotinib

Dose Expansion Crizotinib Combination (Enrolling)

EXPERIMENTAL

MUM patients (previously treated or treatment naive) with human leukocyte antigen (HLA)-A\*02:01 positive status. Includes a nested PK sub-study with Pravastatin (\~22 participants) to evaluate the impact of pravastatin PK profiles after continuous dosing of IDE196. Includes a nested PK Cocktail DDI sub-study (\~15 participants) to evaluate the impact on the PK of bupripion, repaglinide, flurbiprofen, omeprazole, midazolam, dabigatran etexilate, and the exposures of the OAT3 biomarker PDA by IDE196 in combination with crizotinib.

Drug: IDE196; Drug: Crizotinib

Dose Optimization Crizotinib Combination (Enrollment Complete)

EXPERIMENTAL

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

Drug: IDE196; Drug: Crizotinib

Crizotinib Monotherapy with Crossover to Combination (Enrollment Complete)

EXPERIMENTAL

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

Drug: IDE196; Drug: Crizotinib

Interventions

IDE196 DRUG

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

Also known as: Protein Kinase C (PKC) Inhibitor

Crizotinib Monotherapy with Crossover to Combination (Enrollment Complete); Dose Escalation Binimetinib Combination (Enrollment Complete); Dose Escalation Crizotinib Combination (Enrollment Complete); Dose Escalation Monotherapy (Enrollment Complete); Dose Expansion Binimetinib Combination (Enrollment Complete); Dose Expansion Crizotinib Combination (Enrolling); Dose Expansion Monotherapy (Enrollment Complete); Dose Optimization Crizotinib Combination (Enrollment Complete)

Binimetinib DRUG

Binimetinib dosed orally, twice daily for each 28-day cycle

Also known as: MEKTOVI

Dose Escalation Binimetinib Combination (Enrollment Complete); Dose Expansion Binimetinib Combination (Enrollment Complete)

Crizotinib DRUG

Crizotinib dosed orally, twice daily for each 28-day cycle

Also known as: XALKORI

Crizotinib Monotherapy with Crossover to Combination (Enrollment Complete); Dose Escalation Crizotinib Combination (Enrollment Complete); Dose Expansion Crizotinib Combination (Enrolling); Dose Optimization Crizotinib Combination (Enrollment Complete)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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.

You may not qualify if:

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

Sponsors & Collaborators

• IDEAYA Biosciences: lead

Study Sites (15)

UCLA Medical Center

Los Angeles, California, 90095, United States

RECRUITING

San Francisco Oncology Associates

San Francisco, California, 94115, United States

ACTIVE NOT RECRUITING

SCRI - Denver

Denver, Colorado, 80218, United States

RECRUITING

University of Iowa

Iowa City, Iowa, 52242, United States

ACTIVE NOT RECRUITING

Cancer Hematology Centers Western Michigan

Grand Rapids, Michigan, 49503, United States

ACTIVE NOT RECRUITING

Columbia University Medical Center - Herbert Irving Pavilion

New York, New York, 10032, United States

ACTIVE NOT RECRUITING

Duke University Medical Center

Durham, North Carolina, 27710, United States

RECRUITING

University of Cincinnati Cancer Center

Cincinnati, Ohio, 45267, United States

RECRUITING

The Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States

ACTIVE NOT RECRUITING

Sidney Kimmel Cancer Center at Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

RECRUITING

The Sarah Cannon Research Institute/Tennessee Oncology

Nashville, Tennessee, 37203, United States

RECRUITING

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Westmead Hospital

Sydney, New South Wales, Australia

ACTIVE NOT RECRUITING

Queensland

Woolloongabba, 4102, Australia

ACTIVE NOT RECRUITING

Princess Margaret Cancer Centre

Toronto, Ontario, OPG 7-815, Canada

ACTIVE NOT RECRUITING

MeSH Terms

Conditions

Uveal Melanoma; Melanoma; Colorectal Neoplasms

Interventions

Protein Kinase C; binimetinib; Crizotinib

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Uveal Neoplasms; Eye Neoplasms; Neoplasms by Site; Eye Diseases; Uveal Diseases; Skin Neoplasms; Skin Diseases; Skin and Connective Tissue Diseases; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Protein Serine-Threonine Kinases; Protein Kinases; Phosphotransferases (Alcohol Group Acceptor); Phosphotransferases; Transferases; Enzymes; Enzymes and Coenzymes; Intracellular Signaling Peptides and Proteins; Proteins; Amino Acids, Peptides, and Proteins; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Aminopyridines; Pyridines

Study Officials

• George Cole Jr., MD

  gcole@ideayabio.com

  STUDY DIRECTOR

Central Study Contacts

IDEAYA Clinical Trials

CONTACT

855-IDEA-BIO (855-433-2246); IDEAYAClinicalTrials@ideayabio.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 9, 2019
• First Posted: May 13, 2019
• Study Start: June 28, 2019
• Primary Completion (Estimated): January 29, 2027
• Study Completion (Estimated): June 15, 2027
• Last Updated: January 27, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1); US (12); AU (2)