Metastatic Uveal Melanoma
Conditions
Keywords
IDE196, Darovasertib, Protein Kinase C, Metastatic Uveal Melanoma, Melanoma, Ocular Oncology, Ophthalmology, Crizotinib, Ocular melanoma
Brief summary
This is a Phase 2/3, multi-arm, multi-stage, open-label study of human leukocyte antigen (HLA)-A\*02:01 negative participants with metastatic uveal melanoma (MUM) who will be randomized to receive either IDE196 + crizotinib or investigator's choice of treatment (pembrolizumab, ipilimumab + nivolumab, or dacarbazine).
Detailed description
This study is designed as a multi-stage Phase 2 study within a Phase 3 study to evaluate the safety, tolerability, pharmacokinetics, dose-exposure relationship, and anti-tumor activity of IDE196 in combination with crizotinib compared to the comparator arm of investigator's choice of treatment (pembrolizumab, ipilimumab + nivolumab, or dacarbazine). The Phase 2a dose optimization stage will evaluate two doses of IDE196 in combination with crizotinib compared to the comparator arm. Participants will be randomized to the three treatment arms. At the point of optimal IDE196 + crizotinib dose selection, the other dose arm will be dropped with discontinuation of enrollment to that arm. Participants receiving the IDE196 dose (in combination with crizotinib) that is not selected, will be offered the choice to remain on the same dose or change to the chosen optimal dose. The optimal dose will be chosen to complete the Phase 2b portion. The Phase 2b part of the study will continue to enroll the chosen combination dose of IDE196 + crizotinib compared with the comparator arm. Participants will be randomized to the two treatment arms. The Phase 3 part of the study will continue to enroll the chosen combination dose of IDE196 + crizotinib compared with the comparator arm. Participants will be randomized to the two treatment arms to evaluate the primary endpoint of overall survival (OS).
Interventions
DRUGIDE196
Dosed orally, twice daily
DRUGCrizotinib
Dosed orally, twice daily
DRUGPembrolizumab
IV administration every 3 weeks
DRUGIpilimumab
IV administration every 3 weeks for 4 Cycles
DRUGNivolumab
IV administration every 3 Weeks for 4 Cycles, thereafter every 4 Weeks maintenance
DRUGDacarbazine
IV administration every 3 Weeks
Sponsors
IDEAYA Biosciences
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histological or cytological confirmed Metastatic Uveal Melanoma * HLA-A\*02:01 negative * No prior systemic therapy in the metastatic or advanced setting regional or liver-directed therapy. Ablations or surgical resection of oligometastatic disease, and neoadjuvant or adjuvant therapy is allowed * Measurable disease per RECIST 1.1 * Able to be safely administered and absorb study therapy * ECOG performance status 0 or 1 * Life expectancy of ≥3 months * Adequate organ function
Exclusion criteria
* Previous treatment with a PKC inhibitor (including prior treatment with IDE196), an inhibitor directly targeting MET, or an inhibitor directly targeting GNAQ/11 * Concurrent malignant disease * AEs from prior anti-cancer therapy that have not resolved to Grade ≤1 * Symptomatic or untreated central nervous system (CNS) metastases, or CNS metastases that require corticosteroids * High risk of syncope or falls * Known AIDS related illness * Active adrenal insufficiency, active colitis, or active inflammatory bowel disease * History of interstitial lung disease, active pneumonitis, or history of pneumonitis requiring steroids * Active infection requiring systemic antibiotic therapy or active Hepatitis B/C * Major surgery, radiotherapy, or use of hematopoietic colony-stimulating factors (CSF) within 2 weeks prior to start of study drug * Females who are pregnant or breastfeeding * History of severe hypersensitivity reactions (eg, anaphylaxis) to other biologic drugs or monoclonal antibodies * Contraindication for treatment with investigator's choice therapies as per applicable labelling * History of stroke within the last 6 months of the first dose of study drug * Impaired Cardiac function or clinically significant cardiac diseases, including angina pectoris or acute myocardial infarction \<= 6 months prior to start of study treatment * Has any other condition that may increase the risk associated with study participation or may interfere with the interpretation of study results and, in the opinion of the investigator, would make the participant inappropriate for entry into the study, including institutionalization on the basis of an official or court order
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase 2 Progression-Free Survival (PFS) | Approximately 2 years | by blinded independent central review (BICR) of IDE196 + Crizotinib compared to investigator's choice of treatment per RECIST v1.1 |
| Phase 3 Overall Survival (OS) of IDE196 + Crizotinib compared to investigator's choice of treatment. | Approximately 4 years | OS from randomization to date of death due to any cause |
| Phase 2a: To determine the optimal dose of IDE196 + Crizotinib combination for Phase 2B and Phase 3 by evaluating the following: | Approximately 5 months | dose exposure response (safety and efficacy) relationship, plasma concentration profiles and pharmacokinetic (PK) parameters, treatment-emergent Adverse Events (TEAEs), laboratory abnormalities, electrocardiogram (ECG), and vital sign changes and study treatment discontinuation due to AEs. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Phase 2b + 3: Progression-Free Survival (PFS) per Investigator Assessment of IDE196 + Crizotinib compared to investigator's choice of treatment . | Approximately 2 years | PFS per RECIST v1.1 |
| Objective Response Rate (ORR) per BICR and Investigator assessment of IDE196 + Crizotinib compared to investigator's choice of treatment | Approximately 2 years | ORR per RECIST v1.1 |
| Duration of Response (DOR) per BICR and Investigator assessment of IDE196 + Crizotinib compared to investigator's choice of treatment | Approximately 2 years | DOR per RECIST v1.1 |
| Change from baseline over time and between treatment arms in Global health status and quality of life will be assessed using the EORTC QLQ-C30 questionnaire. | Approximately 2 years | The score range for the EORTC QLQ-C30 is from 0 to 100, with higher scores indicating better functioning and better global health status and health-related in EORTC QLQ-C30 scores |
| Change from baseline over time and between treatment arms in | Approximately 2 years | EuroQoL (EQ)-5D-5L scores |
| Best Objective Response (BOR) per BICR and Investigator Assessment of IDE196 + Crizotinib compared to Investigator's choice of treatment | Approximately 2 years | Best Objective Response (BOR) per RECIST v1.1 |
| Disease Control Rate (DCR) per BICR and Investigator Assessment of IDE196 + Crizotinib compared to investigator's choice of treatment. | Approximately 2 years | Disease Control Rate (DCR) per RECIST v1.1 |
| Phase 2a: Dose-exposure-response of IDE196 as measured by correlating the concentration of IDE196 in plasma with safety and efficacy. | Approximately 5 months | Dose exposure response of IDE196. |
| Time to response as assessed by Investigator and BICR | Approximately 2 years | Time to response per RECIST v1.1 |
| Safety of IDE196 + Crizotinib: Incidence of Adverse Events | Approximately 2 years | Treatment emergent adverse events will be summarized by all AEs, including by Grade ≥3, all treatment related AEs, all AEs leading to study drug modifications or discontinuations, all SAEs as measured by CTCAE v5.0. |
| Phase 2a: Dose-exposure-response of Crizotinib measured by correlating the concentration of Crizotinib in plasma with safety and efficacy. | Approximately 5 months | Dose exposure response of Crizotinib |
Countries
Australia, Belgium, Canada, France, Germany, Israel, Italy, Netherlands, Poland, Spain, Switzerland, United Kingdom, United States
Contacts
STUDY_DIRECTORHetal Patel, MD, MSHS, CHCQM
IDEAYA Biosciences
Outcome results
None listed