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
Sex
ALL
Min age
18 Years
Max age
—
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
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.
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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