Study of IDE196 in Patients with Solid Tumors Harboring GNAQ/11 Mutations or PRKC Fusions
- Conditions
- Metastatic Uveal MelanomaColorectal CancerCutaneous MelanomaOther Solid Tumors
- Interventions
- Registration Number
- NCT03947385
- Lead Sponsor
- IDEAYA Biosciences
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 341
-
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 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 Biopsy-eligible patients
- Accessible lesion(s) that permit a total of at least two biopsies without unacceptable risk of a significant procedural complication.
- 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 Exclusion Criteria:
- 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 Exclusion Criteria:
- 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
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Dose Expansion Monotherapy IDE196 RP2D in MUM and non-MUM tumors harboring GNAQ/11 mutations or PRKC fusions (cutaneous melanoma, CRC, other solid tumors) Dose Escalation Binimetinib Combination IDE196 IDE196 dosed orally, twice daily (BID) for each 28-day cycle and Binimetinib dosed orally, twice daily (BID) for each 28-day cycle Dose Expansion Binimetinib Combination IDE196 RP2D in MUM and non-MUM tumors harboring GNAQ/11 mutations (cutaneous melanoma, CRC, other solid tumors) Dose Escalation Crizotinib Combination IDE196 IDE196 dosed orally, twice daily (BID) for each 28-day cycle and Crizotinib dosed orally, twice daily (BID) for each 28-day cycle Dose Expansion Crizotinib Combination IDE196 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 Dose Escalation Monotherapy IDE196 IDE196 dosed orally, twice daily (BID) for each 28-day cycle Dose Escalation Binimetinib Combination Binimetinib IDE196 dosed orally, twice daily (BID) for each 28-day cycle and Binimetinib dosed orally, twice daily (BID) for each 28-day cycle Dose Expansion Binimetinib Combination Binimetinib RP2D in MUM and non-MUM tumors harboring GNAQ/11 mutations (cutaneous melanoma, CRC, other solid tumors) Dose Escalation Crizotinib Combination Crizotinib IDE196 dosed orally, twice daily (BID) for each 28-day cycle and Crizotinib dosed orally, twice daily (BID) for each 28-day cycle Dose Expansion Crizotinib Combination Crizotinib 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 Dose Optimization Crizotinib Combination IDE196 IDE196 dosed orally, twice daily (BID) for each 28-day cycle and Crizotinib dosed orally, twice daily (BID) for each 28-day cycle Dose Optimization Crizotinib Combination Crizotinib IDE196 dosed orally, twice daily (BID) for each 28-day cycle and Crizotinib dosed orally, twice daily (BID) for each 28-day cycle Crizotinib Monotherapy with Crossover to Combination IDE196 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 Crizotinib Monotherapy with Crossover to Combination Crizotinib 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 PK Substudy with Pravastatin (OBTP1B1 Substrate) Crizotinib 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.
- Primary Outcome Measures
Name Time Method Recommended Phase 2 Dose (RP2D) as monotherapy, in combination with Binimetinib, or in combination with Crizotinib Approx. 6 months Determine RP2D of IDE196 as monotherapy, in combination with Binimetinib, or in combination with Crizotinib
Duration of Response for combination with Binimetinib or in combination with Crizotinib Dose Expansion by Blinded Independent Review Committee Approx. 48 months RECIST v1.1
Maximum Tolerated Dose (MTD) 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
Plasma Concentrations of Binimetinib administered in combination with IDE196 Approx. 6 months Pharmacokinetics of Binimetinib in combination with IDE196
Plasma Concentrations of Crizotinib administered in combination with IDE196 Approx. 6 months Pharmacokinetics of Crizotinib in combination with IDE196
Dose-limiting Toxicity (DLT) 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
Plasma Concentrations of IDE196 as monotherapy, in combination with Binimetinib, or in combination with Crizotinib Approx. 6 months Pharmacokinetics of IDE196 as monotherapy, in combination with Binimetinib, or in combination with Crizotinib
Overall Response Rate (ORR) for combination with Binimetinib or in combination with Crizotinib Dose Expansion by Blinded Independent Review Committee Approx. 48 months Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (v1.1) criteria
- Secondary Outcome Measures
Name Time Method ORR by Investigator Approx. 48 months RECIST v1.1
Duration of Response by Investigator Approx. 48 months RECIST v1.1
Numbers of Participants with Adverse Events Approx. 48 months Safety and tolerability of IDE196 either as monotherapy, in combination with Binimetinib, or in combination with Crizotinib
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 Approx. 48 months Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (v1.1) criteria
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 Approx. 48 months RECIST v1.1
Disease Control by Investigator Approx. 48 months RECIST v1.1
Treatment-related pharmacodynamic effect in all patients Approx. 48 months Modulation of signaling proteins in PKC, MAPK, and MET pathways
Trial Locations
- Locations (10)
UCLA Medical Center
🇺🇸Los Angeles, California, United States
San Francisco Oncology Associates
🇺🇸San Francisco, California, United States
Columbia University Medical Center - Herbert Irving Pavilion
🇺🇸New York, New York, United States
Duke University Medical Center
🇺🇸Durham, North Carolina, United States
University of Cincinnati Cancer Center
🇺🇸Cincinnati, Ohio, United States
Sidney Kimmel Cancer Center at Thomas Jefferson University
🇺🇸Philadelphia, Pennsylvania, United States
The Sarah Cannon Research Institute/Tennessee Oncology
🇺🇸Nashville, Tennessee, United States
The University of Texas MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
Westmead Hospital
🇦🇺Sydney, New South Wales, Australia
Princess Margaret Cancer Centre
🇨🇦Toronto, Ontario, Canada