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

NCT ID: NCT03947385

Last Updated: 2024-11-13

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 341 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-06-28
• Study Completion Date: 2027-03-31

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

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Dose Escalation Monotherapy

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

Group Type: EXPERIMENTAL

IDE196

Intervention Type: DRUG

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

Dose Expansion Monotherapy

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

Group Type: EXPERIMENTAL

IDE196

Intervention Type: DRUG

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

Dose Escalation Binimetinib Combination

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

Group Type: EXPERIMENTAL

IDE196

Intervention Type: DRUG

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

Binimetinib

Intervention Type: DRUG

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

Dose Expansion Binimetinib Combination

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

Group Type: EXPERIMENTAL

IDE196

Intervention Type: DRUG

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

Binimetinib

Intervention Type: DRUG

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

Dose Escalation Crizotinib Combination

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

Group Type: EXPERIMENTAL

IDE196

Intervention Type: DRUG

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

Crizotinib

Intervention Type: DRUG

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

Dose Expansion Crizotinib Combination

RP2D in MUM and non-MUM tumors harboring GNAQ/11 mutations (cutaneous melanoma, CRC, other solid tumors) Previously treated MUM, Treatment naïve MUM, MUM patients with human leukocyte antigen (HLA)-A\*02:01 positive status

Group Type: EXPERIMENTAL

IDE196

Intervention Type: DRUG

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

Crizotinib

Intervention Type: DRUG

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

Dose Optimization Crizotinib Combination

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

Group Type: EXPERIMENTAL

IDE196

Intervention Type: DRUG

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

Crizotinib

Intervention Type: DRUG

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

Crizotinib Monotherapy with Crossover to Combination

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

Group Type: EXPERIMENTAL

IDE196

Intervention Type: DRUG

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

Crizotinib

Intervention Type: DRUG

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

PK Substudy with Pravastatin (OBTP1B1 Substrate)

A PK substudy with approximately 18 patients will be nested within the IDE196 and crizotinib combination expansion cohort to evaluate the impact on the pravastatin PK profile by the steady state exposures of IDE196.

Group Type: EXPERIMENTAL

Crizotinib

Intervention Type: DRUG

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

Interventions

IDE196

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

Intervention Type: DRUG

Binimetinib

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

Intervention Type: DRUG

Crizotinib

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

Intervention Type: DRUG

Other Intervention Names

Protein Kinase C (PKC) Inhibitor; MEKTOVI; XALKORI

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

• 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

• 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

• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

IDEAYA Biosciences

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

George Cole Jr., MD

Role: STUDY_DIRECTOR

gcole@ideayabio.com

Locations

UCLA Medical Center

Los Angeles, California, United States

Site Status: RECRUITING

San Francisco Oncology Associates

San Francisco, California, United States

Site Status: RECRUITING

Columbia University Medical Center - Herbert Irving Pavilion

New York, New York, United States

Site Status: RECRUITING

Duke University Medical Center

Durham, North Carolina, United States

Site Status: RECRUITING

University of Cincinnati Cancer Center

Cincinnati, Ohio, United States

Site Status: RECRUITING

Sidney Kimmel Cancer Center at Thomas Jefferson University

Philadelphia, Pennsylvania, United States

Site Status: RECRUITING

The Sarah Cannon Research Institute/Tennessee Oncology

Nashville, Tennessee, United States

Site Status: RECRUITING

The University of Texas MD Anderson Cancer Center

Houston, Texas, United States

Site Status: RECRUITING

Westmead Hospital

Sydney, New South Wales, Australia

Site Status: RECRUITING

Princess Margaret Cancer Centre

Toronto, Ontario, Canada

Site Status: RECRUITING

Countries

United States; Australia; Canada

Central Contacts

IDEAYA Clinical Trials

Role: CONTACT

IDEAYAClinicalTrials@ideayabio.com

+1 650 534 3616

Facility Contacts

Bartosz Chmielowski, MD

Role: primary

BChmielowski@mednet.ucla.edu

Role: primary

clinicalresearch@sutterhealth.org

Wei Alexander, MD

Role: primary

aw3056@cumc.columbia.edu

Carol A Wiggs

Role: primary

cao13@duke.edu

Role: primary

513-584-7698

Marlana Orloff, MD

Role: primary

marlana.orloff@jefferson.edu

askSARAH

Role: primary

844-482-4812

Jordi Ahnert, MD

Role: primary

JRodon@mdanderson.org

Matteo Carlino, MD

Role: primary

+61 288 905 200

Role: backup

02 8890 5200

Melissa Da Ponte

Role: primary

Melissa.DaPonte@uhn.ca

416-946-4501 ext. 5485

Other Identifiers

IDE196-001

Identifier Type: -

Identifier Source: org_study_id