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出境医 / 临床实验 / Study of IDE196 in Patients With Solid Tumors Harboring GNAQ/11 Mutations or PRKC Fusions
Study of IDE196 in Patients With Solid Tumors Harboring GNAQ/11 Mutations or PRKC Fusions
Study Description
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 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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Metastatic Uveal Melanoma Cutaneous Melanoma Colorectal Cancer Other Solid Tumors | Drug: IDE196 Drug: Binimetinib Drug: Crizotinib | Phase 1 Phase 2 |
Study Design
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 254 participants |
| Allocation: | Non-Randomized |
| Intervention Model: | Sequential Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | A Phase 1/2 Study of IDE196 in Patients With Solid Tumors Harboring GNAQ/11 Mutations or PRKC Fusions |
| Actual Study Start Date : | June 28, 2019 |
| Estimated Primary Completion Date : | December 15, 2021 |
| Estimated Study Completion Date : | April 30, 2023 |
Arms and Interventions
| Arm | Intervention/treatment |
|---|---|
|
Experimental: Dose Escalation Monotherapy
IDE196 dosed orally, twice daily (BID) for each 28-day cycle
|
Drug: IDE196
IDE196 dosed orally, twice daily for each 28-day cycle
Other Name: Protein Kinase C (PKC) Inhibitor
|
|
Experimental: Dose Expansion Monotherapy
RP2D in MUM and non-MUM tumors harboring GNAQ/11 mutations or PRKC fusions (cutaneous melanoma, CRC, other solid tumors)
|
Drug: IDE196
IDE196 dosed orally, twice daily for each 28-day cycle
Other Name: Protein Kinase C (PKC) Inhibitor
|
|
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
|
Drug: IDE196
IDE196 dosed orally, twice daily for each 28-day cycle
Other Name: Protein Kinase C (PKC) Inhibitor
Drug: Binimetinib Binimetinib dosed orally, twice daily for each 28-day cycle
Other Name: MEKTOVI
|
|
Experimental: Dose Expansion Binimetinib Combination
RP2D in MUM and non-MUM tumors harboring GNAQ/11 mutations (cutaneous melanoma, CRC, other solid tumors)
|
Drug: IDE196
IDE196 dosed orally, twice daily for each 28-day cycle
Other Name: Protein Kinase C (PKC) Inhibitor
Drug: Binimetinib Binimetinib dosed orally, twice daily for each 28-day cycle
Other Name: MEKTOVI
|
|
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
|
Drug: IDE196
IDE196 dosed orally, twice daily for each 28-day cycle
Other Name: Protein Kinase C (PKC) Inhibitor
Drug: Crizotinib Crizotinib dosed orally, twice daily for each 28-day cycle
Other Name: XALKORI
|
|
Experimental: Dose Expansion Crizotinib Combination
RP2D in MUM and non-MUM tumors harboring GNAQ/11 mutations (cutaneous melanoma, CRC, other solid tumors)
|
Drug: IDE196
IDE196 dosed orally, twice daily for each 28-day cycle
Other Name: Protein Kinase C (PKC) Inhibitor
Drug: Crizotinib Crizotinib dosed orally, twice daily for each 28-day cycle
Other Name: XALKORI
|
|
Experimental: Tablet PK Substudy
IDE196 dosed orally, once on Cycle 1 Day 1; thereafter, twice daily (BID) for each 28-day cycle
|
Drug: IDE196
IDE196 dosed orally, twice daily for each 28-day cycle
Other Name: Protein Kinase C (PKC) Inhibitor
|
Outcome Measures
Primary Outcome Measures :
- Dose-limiting Toxicity (DLT) [ Time Frame: 28 days following first dose of IDE196 as monotherapy, in combination with Binimetinib, or in combination with Crizotinib ]Determine DLT of IDE196 as monotherapy, in combination with Binimetinib, or in combination with Crizotinib
- Maximum Tolerated Dose (MTD) [ Time Frame: 28 days following first dose of IDE196 as monotherapy, in combination with Binimetinib, or in combination with Crizotinib ]Determine MTD 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 [ Time Frame: Approx. 6 months ]Determine RP2D of IDE196 as monotherapy, in combination with Binimetinib, or in combination with Crizotinib
- Plasma Concentrations of IDE196 as monotherapy, in combination with Binimetinib, or in combination with Crizotinib [ Time Frame: Approx. 6 months ]Pharmacokinetics of IDE196 as monotherapy, in combination with Binimetinib, or in combination with Crizotinib
Secondary Outcome Measures :
- Overall Response Rate (ORR) in Dose Expansion by Blinded Independent Review Committee [ Time Frame: Approx. 30 months ]Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (v1.1) criteria
- Duration of Response by Blinded Independent Review Committee [ Time Frame: Approx. 30 months ]RECIST v1.1
- ORR by Investigator [ Time Frame: Approx. 30 months ]RECIST v1.1
- Duration of Response by Investigator [ Time Frame: Approx. 30 months ]RECIST v1.1
- Disease Control by Investigator [ Time Frame: Approx. 30 months ]RECIST v1.1
- Numbers of Participants with Adverse Events [ Time Frame: Approx. 30 months ]Safety and tolerability of IDE196 either as monotherapy, in combination with Binimetinib, or in combination with Crizotinib
Other Outcome Measures:
- Progression-Free Survival [ Time Frame: Approx. 48 months ]RECIST v1.1
- Overall Survival [ Time Frame: Approx. 48 months ]
Eligibility Criteria
| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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:
- Another malignancy
- 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
- Untreated or symptomatic central nervous system metastases
- Human immunodeficiency virus, acquired immunodeficiency syndrome related illness, hepatitis B virus, or hepatitis C virus
- Recent surgery or radiotherapy
- Females who are pregnant or breastfeeding
- Impaired cardiac function
- For patients receiving IDE196 powder-in-capsule (PIC) formulation or crizotinib, allergy to mammalian meat products and gelatin
Binimetinib Combination Additional Exclusion Criteria
- Patient has received prior treatment with a MEK inhibitor
- History of interstitial lung disease
- History of thromboembolic or cerebrovascular events ≤ 12 weeks prior to first dose
- History or current evidence of central serous retinopathy (CSR) or retinal vein occlusion (RVO); History of retinal degenerative disease
- Concurrent neuromuscular disorders that are associated with elevated creatine phosphokinase (CPK)
- Uncontrolled arterial hypertension despite medical treatment
- Allergy to binimetinib or its components
Crizotinib Combination Additional Exclusion Criteria:
- Prior therapy directly targeting ALK, MET, or ROS1
- Spinal cord compression
- Carcinomatous meningitis or leptomeningeal disease
- History of pneumonitis or interstitial lung disease
Contacts and Locations
Contacts
| Contact: IDEAYA Clinical Trials | +1 650 534 3616 | IDEAYAClinicalTrials@ideayabio.com |
Locations
| United States, California | |
| UCLA Medical Center | Recruiting |
| Los Angeles, California, United States, 90095 | |
| Contact: Bartosz Chmielowski, MD BChmielowski@mednet.ucla.edu | |
| United States, Florida | |
| Florida Cancer Specialist South | Recruiting |
| Fort Myers, Florida, United States, 33901 | |
| Contact: James Reeves, MD 239-274-9930 jreeves@flcancer.com | |
| Florida Cancer Specialist North | Recruiting |
| Saint Petersburg, Florida, United States, 33705 | |
| Contact: Vijay Patel, MD 727-895-1143 vpatel@flcancer.com | |
| United States, Missouri | |
| Mosaic Life Care | Recruiting |
| Saint Joseph, Missouri, United States, 64507 | |
| Contact: Rony Abou-Jawde, MD 816-271-1301 rony.abou-jawde@mymlc.com | |
| United States, New York | |
| Columbia University Medical Center - Herbert Irving Pavilion | Recruiting |
| New York, New York, United States, 10032 | |
| Contact: Richard Carvajal, MD 646-317-6330 rdc2150@cumc.columbia.edu | |
| United States, Pennsylvania | |
| Sidney Kimmel Cancer Center at Thomas Jefferson University | Recruiting |
| Philadelphia, Pennsylvania, United States, 19107 | |
| Contact: Sarah Melendez Sarah.melendez@jefferson.edu | |
| Contact: Cynthia Y Perez, BS, CCRP Cynthia.Perez@jefferson.edu | |
| United States, Tennessee | |
| The Sarah Cannon Research Institute/Tennessee Oncology | Recruiting |
| Nashville, Tennessee, United States, 37203 | |
| Contact: askSARAH 844-482-4812 | |
| United States, Texas | |
| The University of Texas MD Anderson Cancer Center | Recruiting |
| Houston, Texas, United States, 77030 | |
| Contact: Filip Janku, MD 713-792-6161 FJanku@mdanderson.org | |
| Australia, New South Wales | |
| Westmead Hospital | Recruiting |
| Sydney, New South Wales, Australia | |
| Contact: Matteo Carlino, MD +61 288 905 200 | |
| Contact 02 8890 5200 | |
Sponsors and Collaborators
IDEAYA Biosciences
| Tracking Information | |||||
|---|---|---|---|---|---|
| First Submitted Date ICMJE | May 9, 2019 | ||||
| First Posted Date ICMJE | May 13, 2019 | ||||
| Last Update Posted Date | February 17, 2021 | ||||
| Actual Study Start Date ICMJE | June 28, 2019 | ||||
| Estimated Primary Completion Date | December 15, 2021 (Final data collection date for primary outcome measure) | ||||
| Current Primary Outcome Measures ICMJE |
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| Original Primary Outcome Measures ICMJE |
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| Change History | |||||
| Current Secondary Outcome Measures ICMJE |
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| Original Secondary Outcome Measures ICMJE |
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| Current Other Pre-specified Outcome Measures |
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| Original Other Pre-specified Outcome Measures |
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| Descriptive Information | |||||
| Brief Title ICMJE | Study of IDE196 in Patients With Solid Tumors Harboring GNAQ/11 Mutations or PRKC Fusions | ||||
| Official Title ICMJE | A Phase 1/2 Study of IDE196 in Patients With Solid Tumors Harboring GNAQ/11 Mutations or PRKC Fusions | ||||
| 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 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. |
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| Detailed Description | Not Provided | ||||
| Study Type ICMJE | Interventional | ||||
| Study Phase ICMJE | Phase 1 Phase 2 |
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| Study Design ICMJE | Allocation: Non-Randomized Intervention Model: Sequential Assignment Masking: None (Open Label) Primary Purpose: Treatment |
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| Condition ICMJE |
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| Intervention ICMJE |
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| Study Arms ICMJE |
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| Publications * | Not Provided | ||||
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* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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| Recruitment Information | |||||
| Recruitment Status ICMJE | Recruiting | ||||
| Estimated Enrollment ICMJE |
254 | ||||
| Original Estimated Enrollment ICMJE |
166 | ||||
| Estimated Study Completion Date ICMJE | April 30, 2023 | ||||
| Estimated Primary Completion Date | December 15, 2021 (Final data collection date for primary outcome measure) | ||||
| Eligibility Criteria ICMJE |
Inclusion Criteria:
Binimetinib Combination Additional Inclusion Criteria: • Adequate cardiac function represented by left ventricular ejection fraction (LVEF) ≥ 50% Crizotinib Combination Additional Inclusion Criteria:
Exclusion Criteria:
Binimetinib Combination Additional Exclusion Criteria
Crizotinib Combination Additional Exclusion Criteria:
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| Sex/Gender ICMJE |
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| Ages ICMJE | 18 Years and older (Adult, Older Adult) | ||||
| Accepts Healthy Volunteers ICMJE | No | ||||
| Contacts ICMJE |
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| Listed Location Countries ICMJE | Australia, United States | ||||
| Removed Location Countries | |||||
| Administrative Information | |||||
| NCT Number ICMJE | NCT03947385 | ||||
| Other Study ID Numbers ICMJE | IDE196-001 | ||||
| Has Data Monitoring Committee | No | ||||
| U.S. FDA-regulated Product |
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| IPD Sharing Statement ICMJE |
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| Responsible Party | IDEAYA Biosciences | ||||
| Study Sponsor ICMJE | IDEAYA Biosciences | ||||
| Collaborators ICMJE | Not Provided | ||||
| Investigators ICMJE | Not Provided | ||||
| PRS Account | IDEAYA Biosciences | ||||
| Verification Date | February 2021 | ||||
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ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |
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