IDE196 (Darovasertib) in Combination with Crizotinib As First-line Therapy in Metastatic Uveal Melanoma
Purpose
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).
Condition
- Metastatic Uveal Melanoma
Eligibility
- Eligible Ages
- Over 18 Years
- Eligible Genders
- All
- Accepts 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 or 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 - Known AIDS related illness or active Hep B/C - Active adrenal insufficiency, active colitis, or active inflammatory bowel disease - History of interstitial lung disease, active pneumonitis, or history of pneumonitis - Active infection requiring systemic antibiotic therapy - Use of hematopoietic colony-stimulating factors (CSF) 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 - 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
Study Design
- Phase
- Phase 2/Phase 3
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Sequential Assignment
- Primary Purpose
- Treatment
- Masking
- None (Open Label)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental Phase 2a Dose Optimization of IDE196 + crizotinib |
Multiple doses of IDE196 will be tested in combination with fixed dose of crizotinib to identify the optimal combination dose. |
|
|
Experimental Phase 2b / 3 Chosen Combination dose of IDE196 + crizotinib |
Chosen combination dose of IDE196 + crizotinib will be tested in additional participants. |
|
|
Active Comparator Phase 2a / 2b / 3 Comparator Arm |
Participants will receive investigator's choice of Pembrolizumab, Ipilimumab + Nivolumab, or Dacarbazine. |
|
Recruiting Locations
Scottsdale, Arizona 85258
La Jolla, California 92093
Los Angeles, California 90024
Los Angeles, California 90025
San Francisco, California 94115
San Francisco, California 94143
Aurora, Colorado 80045
Denver, Colorado 80218
Miami, Florida 33136
Tampa, Florida 33612
Atlanta, Georgia 30342
Boston, Massachusetts 02114
Boston, Massachusetts 02215
Grand Rapids, Michigan 49546
Burnsville, Minnesota 55337
Rochester, Minnesota 55905
Saint Louis, Missouri 63110
Buffalo, New York 14263
New York, New York 10065
Durham, North Carolina 27710
Cleveland, Ohio 44195
Philadelphia, Pennsylvania 19107
Pittsburg, Pennsylvania 15232
Nashville, Tennessee 37203
SCRI Oncology Partners
(844) 482-4812
Dallas, Texas 75246
Dallas, Texas 75390
Houston, Texas 77030
Houston, Texas 77030
More Details
- NCT ID
- NCT05987332
- Status
- Recruiting
- Sponsor
- IDEAYA Biosciences
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.