Durham, North Carolina 27710

  • Other Solid Tumors

Purpose:

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.


Criteria:

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


Study is Available At:


Original ID:

IDE196-001


NCT ID:

NCT03947385


Secondary ID:


Study Acronym:


Brief Title:

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


Official Title:

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


Overall Status:

Recruiting


Study Phase:

Phase 1/Phase 2


Genders:

N/A


Minimum Age:

18 Years


Maximum Age:

N/A


Quick Facts

Healthy Volunteers
Oversight Has DMC
Study Is FDA Regulated
Study Is Section 801
Has Expanded Access

Study Source:

IDEAYA Biosciences


Oversight Authority:

There was an error processing this request


Reasons Why Stopped:


Study Type:

Interventional


Study Design:


Number of Arms:

7


Number of Groups:

0


Total Enrollment:

254


Enrollment Type:

Anticipated


Overall Contact Information

Primary Contact:IDEAYA Clinical Trials
+1 650 534 3616
IDEAYAClinicalTrials@ideayabio.com

Study Dates

Start Date:June 28, 2019
Completion Date:December 31, 2023
Completion Type:Anticipated
Primary Completion Date:December 31, 2022
Primary Completion Type:Anticipated
Verification Date:December 2021
Last Changed Date:May 10, 2022
First Received Date:May 9, 2019

Study Outcomes

Outcome Type:Primary Outcome
Measure:Dose-limiting Toxicity (DLT)
Time Frame:28 days following first dose of IDE196 as monotherapy, in combination with Binimetinib, or in combin
Safety Issues:False
Description:Determine DLT of IDE196 as monotherapy, in combination with Binimetinib, or in combination with Crizotinib
Outcome Type:Primary Outcome
Measure:Maximum Tolerated Dose (MTD)
Time Frame:28 days following first dose of IDE196 as monotherapy, in combination with Binimetinib, or in combin
Safety Issues:False
Description:Determine MTD of IDE196 as monotherapy, in combination with Binimetinib, or in combination with Crizotinib
Outcome Type:Primary Outcome
Measure:Recommended Phase 2 Dose (RP2D) as monotherapy, in combination with Binimetinib, or in combination with Crizotinib
Time Frame:Approx. 6 months
Safety Issues:False
Description:Determine RP2D of IDE196 as monotherapy, in combination with Binimetinib, or in combination with Crizotinib
Outcome Type:Primary Outcome
Measure:Plasma Concentrations of IDE196 as monotherapy, in combination with Binimetinib, or in combination with Crizotinib
Time Frame:Approx. 6 months
Safety Issues:False
Description:Pharmacokinetics of IDE196 as monotherapy, in combination with Binimetinib, or in combination with Crizotinib
Outcome Type:Primary Outcome
Measure:Overall Response Rate (ORR) for combination with Binimetinib or in combination with Crizotinib Dose Expansion by Blinded Independent Review Committee
Time Frame:Approx. 48 months
Safety Issues:False
Description:Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (v1.1) criteria
Outcome Type:Primary Outcome
Measure:Duration of Response for combination with Binimetinib or in combination with Crizotinib Dose Expansion by Blinded Independent Review Committee
Time Frame:Approx. 48 months
Safety Issues:False
Description:RECIST v1.1
Outcome Type:Secondary Outcome
Measure: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
Time Frame:Approx. 48 months
Safety Issues:False
Description:Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (v1.1) criteria
Outcome Type:Secondary Outcome
Measure: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
Time Frame:Approx. 48 months
Safety Issues:False
Description:RECIST v1.1
Outcome Type:Secondary Outcome
Measure:ORR by Investigator
Time Frame:Approx. 48 months
Safety Issues:False
Description:RECIST v1.1
Outcome Type:Secondary Outcome
Measure:Duration of Response by Investigator
Time Frame:Approx. 48 months
Safety Issues:False
Description:RECIST v1.1
Outcome Type:Secondary Outcome
Measure:Disease Control by Investigator
Time Frame:Approx. 48 months
Safety Issues:False
Description:RECIST v1.1
Outcome Type:Secondary Outcome
Measure:Numbers of Participants with Adverse Events
Time Frame:Approx. 48 months
Safety Issues:False
Description:Safety and tolerability of IDE196 either as monotherapy, in combination with Binimetinib, or in combination with Crizotinib
Outcome Type:Secondary Outcome
Measure:Treatment-related pharmacodynamic effect in all patients
Time Frame:Approx. 48 months
Safety Issues:False
Description:Modulation of signaling proteins in PKC, MAPK, and MET pathways

Study Interventions

Intervention Type:Drug
Name:Crizotinib
Description:Crizotinib dosed orally, twice daily for each 28-day cycle
Arm Name:Dose Escalation Crizotinib Combination
Other Name:XALKORI
Intervention Type:Drug
Name:Binimetinib
Description:Binimetinib dosed orally, twice daily for each 28-day cycle
Arm Name:Dose Escalation Binimetinib Combination
Other Name:MEKTOVI
Intervention Type:Drug
Name:IDE196
Description:IDE196 dosed orally, twice daily for each 28-day cycle
Arm Name:Dose Escalation Binimetinib Combination
Other Name:Protein Kinase C (PKC) Inhibitor

Study Arms

Study Arm Type:Experimental
Arm Name:Dose Escalation Monotherapy
Description:IDE196 dosed orally, twice daily (BID) for each 28-day cycle
Study Arm Type:Experimental
Arm Name:Dose Expansion Monotherapy
Description:RP2D in MUM and non-MUM tumors harboring GNAQ/11 mutations or PRKC fusions (cutaneous melanoma, CRC, other solid tumors)
Study Arm Type:Experimental
Arm Name:Tablet PK Substudy
Description:IDE196 dosed orally, once on Cycle 1 Day 1; thereafter, twice daily (BID) for each 28-day cycle
Study Arm Type:Experimental
Arm Name:Dose Expansion Crizotinib Combination
Description:RP2D in MUM and non-MUM tumors harboring GNAQ/11 mutations (cutaneous melanoma, CRC, other solid tumors)
Study Arm Type:Experimental
Arm Name:Dose Escalation Crizotinib Combination
Description:IDE196 dosed orally, twice daily (BID) for each 28-day cycle and Crizotinib dosed orally, twice daily (BID) for each 28-day cycle
Study Arm Type:Experimental
Arm Name:Dose Expansion Binimetinib Combination
Description:RP2D in MUM and non-MUM tumors harboring GNAQ/11 mutations (cutaneous melanoma, CRC, other solid tumors)
Study Arm Type:Experimental
Arm Name:Dose Escalation Binimetinib Combination
Description:IDE196 dosed orally, twice daily (BID) for each 28-day cycle and Binimetinib dosed orally, twice daily (BID) for each 28-day cycle

Study Agencies

Agency Class:Industry
Agency Type:Lead Sponsor
Agency Name:IDEAYA Biosciences

Sample and Retention Information

There are no available Sample and Retention Information

Study References

There are no available Study References

Data Source: ClinicalTrials.gov

Date Processed: February 02, 2023

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