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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03947385




Registration number
NCT03947385
Ethics application status
Date submitted
9/05/2019
Date registered
13/05/2019
Date last updated
13/11/2024

Titles & IDs
Public title
Study of IDE196 in Patients with Solid Tumors Harboring GNAQ/11 Mutations or PRKC Fusions
Scientific title
A Phase 1/2 Study of IDE196 in Patients with Solid Tumors Harboring GNAQ/11 Mutations or PRKC Fusions
Secondary ID [1] 0 0
IDE196-001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Metastatic Uveal Melanoma 0 0
Cutaneous Melanoma 0 0
Colorectal Cancer 0 0
Other Solid Tumors 0 0
Condition category
Condition code
Cancer 0 0 0 0
Malignant melanoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - IDE196
Treatment: Drugs - Binimetinib
Treatment: Drugs - Crizotinib

Experimental: Dose Escalation Monotherapy - IDE196 dosed orally, twice daily (BID) for each 28-day cycle

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

Experimental: 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

Experimental: Dose Expansion Binimetinib Combination - RP2D in MUM and non-MUM tumors harboring GNAQ/11 mutations (cutaneous melanoma, CRC, other solid tumors)

Experimental: 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

Experimental: 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

Experimental: 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

Experimental: 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

Experimental: 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.


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

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

Treatment: Drugs: Crizotinib
Crizotinib dosed orally, twice daily for each 28-day cycle
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Dose-limiting Toxicity (DLT)
Timepoint [1] 0 0
28 days following first dose of IDE196 as monotherapy, in combination with Binimetinib, or in combination with Crizotinib
Primary outcome [2] 0 0
Maximum Tolerated Dose (MTD)
Timepoint [2] 0 0
28 days following first dose of IDE196 as monotherapy, in combination with Binimetinib, or in combination with Crizotinib
Primary outcome [3] 0 0
Recommended Phase 2 Dose (RP2D) as monotherapy, in combination with Binimetinib, or in combination with Crizotinib
Timepoint [3] 0 0
Approx. 6 months
Primary outcome [4] 0 0
Plasma Concentrations of IDE196 as monotherapy, in combination with Binimetinib, or in combination with Crizotinib
Timepoint [4] 0 0
Approx. 6 months
Primary outcome [5] 0 0
Plasma Concentrations of Crizotinib administered in combination with IDE196
Timepoint [5] 0 0
Approx. 6 months
Primary outcome [6] 0 0
Plasma Concentrations of Binimetinib administered in combination with IDE196
Timepoint [6] 0 0
Approx. 6 months
Primary outcome [7] 0 0
Overall Response Rate (ORR) for combination with Binimetinib or in combination with Crizotinib Dose Expansion by Blinded Independent Review Committee
Timepoint [7] 0 0
Approx. 48 months
Primary outcome [8] 0 0
Duration of Response for combination with Binimetinib or in combination with Crizotinib Dose Expansion by Blinded Independent Review Committee
Timepoint [8] 0 0
Approx. 48 months
Secondary outcome [1] 0 0
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
Timepoint [1] 0 0
Approx. 48 months
Secondary outcome [2] 0 0
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
Timepoint [2] 0 0
Approx. 48 months
Secondary outcome [3] 0 0
ORR by Investigator
Timepoint [3] 0 0
Approx. 48 months
Secondary outcome [4] 0 0
Duration of Response by Investigator
Timepoint [4] 0 0
Approx. 48 months
Secondary outcome [5] 0 0
Disease Control by Investigator
Timepoint [5] 0 0
Approx. 48 months
Secondary outcome [6] 0 0
Numbers of Participants with Adverse Events
Timepoint [6] 0 0
Approx. 48 months
Secondary outcome [7] 0 0
Treatment-related pharmacodynamic effect in all patients
Timepoint [7] 0 0
Approx. 48 months

Eligibility
Key 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

* 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

* 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

* 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
28/06/2019
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
31/03/2027
Actual
Sample size
Target
341
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
Westmead Hospital - Sydney
Recruitment postcode(s) [1] 0 0
- Sydney
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
New York
Country [3] 0 0
United States of America
State/province [3] 0 0
North Carolina
Country [4] 0 0
United States of America
State/province [4] 0 0
Ohio
Country [5] 0 0
United States of America
State/province [5] 0 0
Pennsylvania
Country [6] 0 0
United States of America
State/province [6] 0 0
Tennessee
Country [7] 0 0
United States of America
State/province [7] 0 0
Texas
Country [8] 0 0
Canada
State/province [8] 0 0
Ontario

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
IDEAYA Biosciences
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/study/NCT03947385
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
George Cole Jr., MD
Address 0 0
[email protected]
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
IDEAYA Clinical Trials
Address 0 0
Country 0 0
Phone 0 0
+1 650 534 3616
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT03947385