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

Colorectal Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03947385
• Other study ID #: IDE196-001
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: June 28, 2019
• Est. completion date: May 31, 2025

Study information

• Verified date: November 2023
• Source: IDEAYA Biosciences
• Contact: IDEAYA Clinical Trials
• Phone: +1 650 534 3616
• Email: IDEAYAClinicalTrials[@]ideayabio.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 278
• Est. completion date: May 31, 2025
• Est. primary completion date: October 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

Related Conditions & MeSH terms

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

Intervention

Drug:
• IDE196
IDE196 dosed orally, twice daily for each 28-day cycle
• Binimetinib
Binimetinib dosed orally, twice daily for each 28-day cycle
• Crizotinib
Crizotinib dosed orally, twice daily for each 28-day cycle

Locations

Country	Name	City	State
Australia	Westmead Hospital	Sydney	New South Wales
Canada	Princess Margaret Cancer Centre	Toronto	Ontario
United States	University of Cincinnati Cancer Center	Cincinnati	Ohio
United States	Duke University Medical Center	Durham	North Carolina
United States	Florida Cancer Specialist South	Fort Myers	Florida
United States	The University of Texas MD Anderson Cancer Center	Houston	Texas
United States	UCLA Medical Center	Los Angeles	California
United States	The Sarah Cannon Research Institute/Tennessee Oncology	Nashville	Tennessee
United States	Columbia University Medical Center - Herbert Irving Pavilion	New York	New York
United States	Sidney Kimmel Cancer Center at Thomas Jefferson University	Philadelphia	Pennsylvania
United States	Mosaic Life Care	Saint Joseph	Missouri
United States	Florida Cancer Specialist North	Saint Petersburg	Florida
United States	San Francisco Oncology Associates	San Francisco	California
United States	HonorHealth Research Institute	Scottsdale	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
IDEAYA Biosciences

Countries where clinical trial is conducted

United States,  Australia,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Progression-Free Survival	RECIST v1.1	Approx. 48 months
Other	Overall Survival	From date of First Dose to End of Follow-up	Approx. 48 months
Other	Reduction in tumor burden by total volumetric measurement	Maximum reduction in tumor burden relative to response	Approx. 48 months
Other	Treatment-related gene signatures and/or molecular profiling	Modulation of gene signatures and/or molecular profiles	Approx. 48 months
Other	Treatment-related changes in tumor tissue or cell-free DNA from blood	Modulation of tissue or cell-free DNA expression	Approx. 48 months
Primary	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
Primary	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
Primary	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
Primary	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
Primary	Plasma Concentrations of Crizotinib administered in combination with IDE196	Pharmacokinetics of Crizotinib in combination with IDE196	Approx. 6 months
Primary	Plasma Concentrations of Binimetinib administered in combination with IDE196	Pharmacokinetics of Binimetinib in combination with IDE196	Approx. 6 months
Primary	Overall Response Rate (ORR) for combination with Binimetinib or in combination with Crizotinib Dose Expansion by Blinded Independent Review Committee	Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (v1.1) criteria	Approx. 48 months
Primary	Duration of Response for combination with Binimetinib or in combination with Crizotinib Dose Expansion by Blinded Independent Review Committee	RECIST v1.1	Approx. 48 months
Secondary	Overall Response Rate (ORR) for combination with Binimetinib or in combination with Crizotinib in Dose Escalation and all combination cohorts by Blinded Independent Review Committee	Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (v1.1) criteria	Approx. 48 months
Secondary	Duration of Response for combination with Binimetinib or in combination with Crizotinib in Dose Escalation and in all combination cohorts by Blinded Independent Review Committee	RECIST v1.1	Approx. 48 months
Secondary	ORR by Investigator	RECIST v1.1	Approx. 48 months
Secondary	Duration of Response by Investigator	RECIST v1.1	Approx. 48 months
Secondary	Disease Control by Investigator	RECIST v1.1	Approx. 48 months
Secondary	Numbers of Participants with Adverse Events	Safety and tolerability of IDE196 either as monotherapy, in combination with Binimetinib, or in combination with Crizotinib	Approx. 48 months
Secondary	Treatment-related pharmacodynamic effect in all patients	Modulation of signaling proteins in PKC, MAPK, and MET pathways	Approx. 48 months