Active, not recruiting
Phase 2/3
IDE196 (Darovasertib) in Combination With Crizotinib as First-line Therapy in Metastatic Uveal Melanoma
Condition(s) studied
Metastatic Uveal Melanoma
Investigational drug(s) / intervention(s)
IDE196CrizotinibPembrolizumabIpilimumabNivolumabDacarbazine
IDE196: Dosed orally, twice daily
Crizotinib: Dosed orally, twice daily
Pembrolizumab: IV administration every 3 weeks
Ipilimumab: IV administration every 3 weeks for 4 Cycles
Nivolumab: IV administration every 3 Weeks for 4 Cycles, thereafter every 4 Weeks maintenance
Dacarbazine: IV administration every 3 Weeks
Study 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).
Eligibility
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
Primary outcome measure(s)
- 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.
- 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
Trial sites (68)
| Facility | City | Region | Status |
| Honor Health |
Scottsdale |
Arizona |
|
| Moores Cancer Center |
La Jolla |
California |
|
| UCLA Medical Center |
Los Angeles |
California |
|
| The Angeles Clinic and Research Institute |
Los Angeles |
California |
|
| California Pacific Medical Center (CPMC) |
San Francisco |
California |
|
| University of California San Francisco |
San Francisco |
California |
|
| University of Colorado Cancer Center |
Aurora |
Colorado |
|
| SCRI at HealthONE |
Denver |
Colorado |
|
| University of Miami Sylvester Comprehensive Cancer Center |
Miami |
Florida |
|
| Moffitt Cancer Center |
Tampa |
Florida |
|
| Northside Hospital Atlanta |
Atlanta |
Georgia |
|
| University of Iowa |
Iowa City |
Iowa |
|
| Massachusetts General Hospital |
Boston |
Massachusetts |
|
| Dana Farber Cancer Institute |
Boston |
Massachusetts |
|
| The Cancer and Hematology Centers |
Grand Rapids |
Michigan |
|
| Minnesota Oncology Hematology, P.A. |
Burnsville |
Minnesota |
|
| Mayo Clinic |
Rochester |
Minnesota |
|
| Washington University School of Medicine |
St Louis |
Missouri |
|
| Roswell Park Cancer Institute |
Buffalo |
New York |
|
| Northwell Health |
Manhasset |
New York |
|
| Memorial Sloan Kettering Cancer Center |
New York |
New York |
|
| Duke University Health System |
Durham |
North Carolina |
|
| University of Cincinnati |
Cincinnati |
Ohio |
|
| The Cleveland Clinic Foundation |
Cleveland |
Ohio |
|
| Thomas Jefferson University |
Philadelphia |
Pennsylvania |
|
| University of Pittsburgh Medical Center |
Pittsburgh |
Pennsylvania |
|
| SCRI Oncology Partners |
Nashville |
Tennessee |
|
| Texas Oncology- DFW |
Dallas |
Texas |
|
| UT Southwestern Medical Center |
Dallas |
Texas |
|
| Houston Methodist Cancer Center |
Houston |
Texas |
|
| MD Anderson Cancer Center |
Houston |
Texas |
|
| Westmead Hospital |
Sydney |
New South Wales |
|
| Princess Alexander Hospital |
Brisbane |
Queensland |
|
| Peter MacCallum Cancer Centre |
Melbourne |
Victoria |
|
| Alfred Health |
Melbourne |
Victoria |
|
| Sir Charles Gairdner Hospital |
Perth |
Washington |
|
| Queen Elizabeth Hospital |
Adelaide |
Australia |
|
| Cliniques Universitaires Saint Luc |
Brussels |
Belgium |
|
| Algemene Medische Oncologie UZ |
Leuven |
Belgium |
|
| Cross Cancer Institute, University of Alberta |
Edmonton |
Alberta |
|
+ 28 more sites — see the full list on the official registry below.