Colorectal Cancer, Cutaneous Melanoma, Metastatic Uveal Melanoma, Other Solid Tumors
Conditions
Keywords
Metastatic Uveal Melanoma, Uveal Melanoma, Protein Kinase C, Ophthalmology, Ocular Oncology, Darovasertib, IDE196, Ocular Melanoma
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.
Interventions
DRUGIDE196
IDE196 dosed orally, twice daily for each 28-day cycle
DRUGBinimetinib
Binimetinib dosed orally, twice daily for each 28-day cycle
DRUGCrizotinib
Crizotinib dosed orally, twice daily for each 28-day cycle
Sponsors
IDEAYA Biosciences
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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 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.
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| Incidence of Adverse Events | Approx. 8 months | Safety and tolerability of IDE196 either as monotherapy, in combination with Binimetinib, or in combination with Crizotinib |
| 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 |
| 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 |
| 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 |
| Plasma Concentrations of Crizotinib administered in combination with IDE196 | Approx. 6 months | Pharmacokinetics of Crizotinib in combination with IDE196 |
| Plasma Concentrations of Binimetinib administered in combination with IDE196 | Approx. 6 months | Pharmacokinetics of Binimetinib in combination with IDE196 |
| Overall Response Rate (ORR) of IDE196 monotherapy, in combination with Binimetinib, and in combination with Crizotinib in Dose Expansion cohorts by Investigator response assessment | Approx. 8 months | Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (v1.1) criteria |
| Duration of Response (DOR) of IDE196 monotherapy, in combination with Binimetinib, and in combination with Crizotinib in Dose Expansion cohorts by Investigator response assessment | Approx. 8 months | RECIST v1.1 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival (PFS) of IDE196 monotherapy, in combination with Binimetinib, and in combination with Crizotinib in Dose Expansion cohorts by Investigator response assessment | Approx. 18 months | RECIST v1.1 |
| Overall Response Rate (ORR) of IDE196 monotherapy, in combination with Binimetinib, and in combination with Crizotinib in Dose Expansion cohorts and by prior treatment status (pretreated or treatment naive) by Investigator response assessment | Approx. 18 months | Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (v1.1) criteria |
| Duration of Response (DOR) of IDE196 monotherapy, in combination with Binimetinib, and in combination with Crizotinib in Dose Expansion cohorts by prior treatment status (pretreated or treatment naive) by Investigator response assessment | Approx. 18 months | RECIST v1.1 |
| Disease Control Rate (DCR) by Investigator | Approx. 18 months | RECIST v1.1 |
| Area under the plasma concentration versus time curve (AUC) | Approx. 8 months | PK parameters of bupropion, hydroxybupropion, repaglinide, flurbiprofen, omeprazole, midazolam, total dabigatran (dabigtran+glucuronide), and the exposures of PDA (as data permits) |
| Area under the plasma concentration curve from time zero extrapolated to infinity (AUCinf) | Approx. 8 months | PK parameters of bupropion, hydroxybupropion, repaglinide, flurbiprofen, omeprazole, midazolam, total dabigatran (dabigtran+glucuronide), and the exposures of PDA (as data permits) |
| Area under the plasma concentration curve from time zero to the last measurable concentration time (AUC0-t) | Approx. 8 months | PK parameters of bupropion, hydroxybupropion, repaglinide, flurbiprofen, omeprazole, midazolam, total dabigatran (dabigtran+glucuronide), and the exposures of PDA (as data permits) |
| Area under the plasma concentration curve extrapolating the percentage of total drug exposure (AUC%extra) | Approx. 8 months | PK parameters of bupropion, hydroxybupropion, repaglinide, flurbiprofen, omeprazole, midazolam, total dabigatran (dabigtran+glucuronide), and the exposures of PDA (as data permits) |
| Peak Plasma Concentration (Cmax) | Approx. 8 months | PK parameters of bupropion, hydroxybupropion, repaglinide, flurbiprofen, omeprazole, midazolam, total dabigatran (dabigtran+glucuronide), and the exposures of PDA (as data permits) |
| Time to maximum plasma concentration (Tmax) | Approx. 8 months | PK parameters of bupropion, hydroxybupropion, repaglinide, flurbiprofen, omeprazole, midazolam, total dabigatran (dabigtran+glucuronide), and the exposures of PDA (as data permits) |
| Elimination half-life of Plasma Concentration levels (T1/2) | Approx. 8 months | PK parameters of bupropion, hydroxybupropion, repaglinide, flurbiprofen, omeprazole, midazolam, total dabigatran (dabigtran+glucuronide), and the exposures of PDA (as data permits) |
Countries
Australia, Canada, United States
Contacts
CONTACTIDEAYA Clinical Trials
STUDY_DIRECTORGeorge Cole Jr., MD
gcole@ideayabio.com
Outcome results
None listed