Clinical trial NCT05987332: IDE196 (Darovasertib) in Combination With Crizotinib as First-line Therapy in Metastatic Uveal Melanoma
Official title: IDE196 (Darovasertib) in Combination With Crizotinib Versus Investigator's Choice of Treatment as First-line Therapy in HLA-A2 Negative Metastatic Uveal Melanoma (DAR-UM-2)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
PHASE3
Conditions: Metastatic Uveal Melanoma
Keywords: IDE196
Darovasertib
Protein Kinase C
Metastatic Uveal Melanoma
Melanoma
Ocular Oncology
Ophthalmology
Crizotinib
Ocular melanoma
Lead sponsor: IDEAYA Biosciences
Sponsor class: INDUSTRY
First posted: 2023-08-14
Enrollment: 420
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Progression-Free Survival (PFS) by blinded independent central review (BICR) of IDE196 + Crizotinib compared to investigator's choice of treatment
timeFrame: Approximately 2 years
measure: Overall Survival (OS) of IDE196 + Crizotinib compared to investigator's choice of treatment
timeFrame: Approximately 4 years
Secondary outcomes:
measure: Safety of IDE196 + Crizotinib: Incidence of Adverse Events
timeFrame: Approximately 2 years
measure: Phase 2a: Dose exposure response of IDE196
timeFrame: Approximately 5 months
measure: Phase 2a: Dose exposure response of Crizotinib
timeFrame: Approximately 5 months
measure: Progression-Free Survival (PFS) per Investigator of IDE196 + Crizotinib compared to investigator's choice of treatment
timeFrame: Approximately 2 years
measure: Objective Response Rate (ORR) per BICR and Investigator assessment of IDE196 + Crizotinib compared to investigator's choice of treatment
timeFrame: Approximately 2 years
measure: Duration of Response (DOR) per BICR and Investigator assessment of IDE196 + Crizotinib compared to investigator's choice of treatment
timeFrame: Approximately 2 years
measure: Change from baseline over time and between treatment arms in EORTC QLQ-C30
timeFrame: Approximately 2 years
measure: Change from baseline over time and between treatment arms in EuroQoL (EQ)-5D-5L scores
timeFrame: Approximately 2 years
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Honor Health
state: Arizona
city: La Jolla
country: United States
facility: Moores Cancer Center
state: California
city: Los Angeles
country: United States
facility: UCLA Medical Center
state: California
city: Los Angeles
country: United States
facility: The Angeles Clinic and Research Institute
state: California
city: San Francisco
country: United States
facility: California Pacific Medical Center (CPMC)
state: California
city: San Francisco
country: United States
facility: University of California San Francisco
state: California
city: Aurora
country: United States
facility: University of Colorado Cancer Center
state: Colorado
city: Denver
country: United States
facility: SCRI at HealthONE
state: Colorado
city: Miami
country: United States
facility: University of Miami Sylvester Comprehensive Cancer Center
state: Florida
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: Atlanta
country: United States
facility: Northside Hospital Atlanta
state: Georgia
city: Iowa City
country: United States
facility: University of Iowa
state: Iowa
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Grand Rapids
country: United States
facility: The Cancer and Hematology Centers
state: Michigan
city: Burnsville
country: United States
facility: Minnesota Oncology Hematology, P.A.
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: Manhasset
country: United States
facility: Northwell Health
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Durham
country: United States
facility: Duke University Health System
state: North Carolina
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
city: Cleveland
country: United States
facility: The Cleveland Clinic Foundation
state: Ohio
city: Philadelphia
country: United States
facility: Thomas Jefferson University
state: Pennsylvania
city: Pittsburg
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
city: Nashville
country: United States
facility: SCRI Oncology Partners
state: Tennessee
city: Dallas
country: United States
facility: Texas Oncology- DFW
state: Texas
city: Dallas
country: United States
facility: UT Southwestern Medical Center
state: Texas
city: Houston
country: United States
facility: Houston Methodist Cancer Center
state: Texas
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Sydney
country: Australia
facility: Westmead Hospital
state: New South Wales
city: Brisbane
country: Australia
facility: Princess Alexander Hospital
state: Queensland
city: Melbourne
country: Australia
facility: Peter MacCallum Cancer Centre
state: Victoria
city: Melbourne
country: Australia
facility: Alfred Health
state: Victoria
city: Perth
country: Australia
facility: Sir Charles Gairdner Hospital
state: Washington
city: Adelaide
country: Australia
facility: Queen Elizabeth Hospital
city: Brussels
country: Belgium
facility: Cliniques Universitaires Saint Luc
city: Edmonton
country: Canada
facility: Cross Cancer Institute, University of Alberta
state: Alberta
city: Vancouver
country: Canada
facility: BC Cancer Agency
state: British Columbia
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre
state: Ontario
city: Montréal
country: Canada
facility: Centre Hospitalier de l'Universite de Montreal- CHUM
state: Quebec
city: Lyon
country: France
facility: The Leon Berard Center
city: Paris
country: France
facility: Institut Curie
city: Heidelberg
country: Germany
facility: NCT Heidelberg
state: Baden- Württemberg
city: Essen
country: Germany
facility: Universitätsklinikum Essen (AöR)
state: North Rhine-Westphalia
city: Köln
country: Germany
facility: Universitätsklinikum Köln
state: North Rhine-Westphalia
city: Dresden
country: Germany
facility: Universitätsklinikum Carl Gustav Carus Dresden
state: Saxony
city: Berlin
country: Germany
facility: Charité - Universitätsmedizin Berlin
city: Jerusalem
country: Israel
facility: Hadassah Medical Center
city: Ramat-Gan
country: Israel
facility: Sheba Medical Center
city: Milano
country: Italy
facility: Fondazione IRCCS Istituto Nazionale dei Tumori
city: Napoli
country: Italy
facility: Istituto Nazionale dei Tumori Fondazione Pascale
city: Roma
country: Italy
facility: Fondazione Policlinico Gemelli IRCCS
city: Siena
country: Italy
facility: AOUS Policlinico Le Scotte
city: Leiden
country: Netherlands
facility: LUMC (Leids Universitair Medisch Centrum)
city: Gdańsk
country: Poland
facility: Ośrodek Badań Klinicznych Wczesnych Faz, Uniwersyteckie Centrum Kliniczne w Gdańsku
city: Warsaw
country: Poland
facility: Narodowy Instytut Onkologii im. Marii Skłodowskiej-Curie Państwowy Instytut Badawczy
city: L'Hospitalet de Llobregat
country: Spain
facility: Catalan Institute of Oncology
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Santiago de Compostela
country: Spain
facility: Hospital Clínico Universitario de Santiago de Compostela
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen Macarena
city: Valencia
country: Spain
facility: Hospital General Universitario Valencia
city: Zuerich
country: Switzerland
facility: Dermatologische Klinik, USZ Flughafen Geschoss 7 - Klinische Forschung
city: Glasgow
country: United Kingdom
facility: The Beatson West of Scotland Cancer Centre
city: Northwood
country: United Kingdom
facility: Mount Vernon Cancer Centre East & North Herts NHS Trust
city: Wirral
country: United Kingdom
facility: The Clatterbridge Cancer Centre NHS Foundation Trust
Study officials:
affiliation: IDEAYA Biosciences
name: Hetal Patel, MD, MSHS, CHCQM
role: STUDY_DIRECTOR
References: