IDE196 (Darovasertib) in Combination With Crizotinib as First-line Therapy in Metastatic Uveal Melanoma

Metastatic Uveal Melanoma Clinical Trial

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05987332
• Other study ID #: IDE196-002
• Status: Recruiting
• Phase: Phase 2/Phase 3
• Start date: October 31, 2023
• Est. completion date: January 15, 2028

Study information

• Verified date: June 2024
• Source: IDEAYA Biosciences
• Contact: IDEAYA Clinical Trials
• Phone: 1 650-534-3616
• Email: IDEAYAClinicalTrials[@]ideayabio.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 380
• Est. completion date: January 15, 2028
• Est. primary completion date: January 15, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

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, or 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

• Active HIV infection or 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

• 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

Related Conditions & MeSH terms

• Melanoma
• Metastatic Uveal Melanoma
• Uveal Neoplasms

Intervention

Drug:
• 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

Locations

Country	Name	City	State
Australia	Queen Elizabeth Hospital	Adelaide
Australia	Princess Alexander Hospital	Brisbane	Queensland
Australia	Alfred Health	Melbourne	Victoria
Australia	Sir Charles Gairdner Hospital	Perth	Western Australia
Australia	Westmead Hospital	Sydney	New South Wales
Belgium	Cliniques Universitaires Saint Luc	Brussels
Canada	Cross Cancer Institute, University of Alberta	Edmonton	Alberta
Canada	Centre Hospitalier de l'Universite de Montreal- CHUM	Montréal	Quebec
Canada	Princess Margaret Cancer Centre	Toronto	Ontario
France	The Leon Berard Center	Lyon
France	Institut Curie	Paris
Germany	Charité - Universitätsmedizin Berlin	Berlin
Germany	Universitätsklinikum Carl Gustav Carus Dresden	Dresden	Saxony
Germany	Universitätsklinikum Essen (AöR)	Essen	North Rhine-Westphalia
Germany	NCT Heidelberg	Heidelberg	Baden- Württemberg
Germany	Universitätsklinikum Köln	Köln	North Rhine-Westphalia
Israel	Hadassah Medical Center	Jerusalem
Israel	Sheba Medical Center	Ramat-Gan
Italy	Fondazione IRCCS Istituto Nazionale dei Tumori	Milano
Italy	Istituto Nazionale dei Tumori Fondazione Pascale	Napoli
Italy	Fondazione Policlinico Gemelli IRCCS	Roma
Italy	AOUS Policlinico Le Scotte	Siena
Netherlands	LUMC (Leids Universitair Medisch Centrum)	Leiden
Poland	Osrodek Badan Klinicznych Wczesnych Faz, Uniwersyteckie Centrum Kliniczne w Gdansku	Gdansk
Poland	Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie Panstwowy Instytut Badawczy	Warsaw
Spain	Catalan Institute of Oncology	L'Hospitalet de Llobregat
Spain	Hospital Universitario La Paz	Madrid
Spain	Hospital Clínico Universitario de Santiago de Compostela	Santiago de Compostela
Spain	Hospital Universitario Virgen Macarena	Sevilla
Spain	Hospital General Universitario Valencia	Valencia
Switzerland	Dermatologische Klinik, USZ Flughafen Geschoss 7 - Klinische Forschung	Zuerich
United Kingdom	The Beatson West of Scotland Cancer Centre	Glasgow
United Kingdom	Mount Vernon Cancer Centre East & North Herts NHS Trust	Northwood
United Kingdom	The Clatterbridge Cancer Centre NHS Foundation Trust	Wirral
United States	Northside Hospital Atlanta	Atlanta	Georgia
United States	University of Colorado Cancer Center	Aurora	Colorado
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	Minnesota Oncology Hematology, P.A.	Burnsville	Minnesota
United States	University of Cincinnati	Cincinnati	Ohio
United States	The Cleveland Clinic Foundation	Cleveland	Ohio
United States	Texas Oncology- DFW	Dallas	Texas
United States	UT Southwestern Medical Center	Dallas	Texas
United States	SCRI at HealthONE	Denver	Colorado
United States	Duke University Health System	Durham	North Carolina
United States	The Cancer and Hematology Centers	Grand Rapids	Michigan
United States	Houston Methodist Cancer Center	Houston	Texas
United States	MD Anderson Cancer Center	Houston	Texas
United States	University of Iowa	Iowa City	Iowa
United States	Moores Cancer Center	La Jolla	California
United States	The Angeles Clinic and Research Institute	Los Angeles	California
United States	UCLA Medical Center	Los Angeles	California
United States	Northwell Health	Manhasset	New York
United States	University of Miami Sylvester Comprehensive Cancer Center	Miami	Florida
United States	SCRI- Tennessee Oncology	Nashville	Tennessee
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Thomas Jefferson University	Philadelphia	Pennsylvania
United States	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania
United States	Mayo Clinic	Rochester	Minnesota
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	California Pacific Medical Center (CPMC)	San Francisco	California
United States	University of California San Francisco	San Francisco	California
United States	Honor Health	Scottsdale	Arizona
United States	Moffitt Cancer Center	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
IDEAYA Biosciences

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Canada,  France,  Germany,  Israel,  Italy,  Netherlands,  Poland,  Spain,  Switzerland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-Free Survival (PFS) by blinded independent central review (BICR) of IDE196 + Crizotinib compared to investigator's choice of treatment	PFS per RECIST 1.1	Approximately 2 years
Primary	Overall Survival (OS) of IDE196 + Crizotinib compared to investigator's choice of treatment	OS from randomization to date of death due to any cause	Approximately 4 years
Secondary	Safety of IDE196 + Crizotinib: Incidence of Adverse Events	Treatment emergent adverse events will be summarized by all AEs, all Grade 3-4-5 AEs, all treatment related AEs, all AEs leading to study drug modifications or discontinuations, all SAEs as measured by CTCAE V5.0	Approximately 2 years
Secondary	Phase 2a: Dose exposure response of IDE196	Dose-exposure-response of IDE196 as measured by concentration of IDE196 in plasma	Approximately 5 months
Secondary	Phase 2a: Dose exposure response of Crizotinib	Dose-exposure-response of Crizotinib as measured by concentration of Crizotinib in plasma	Approximately 5 months
Secondary	Progression-Free Survival (PFS) per Investigator of IDE196 + Crizotinib compared to investigator's choice of treatment	PFS per RECIST 1.1	Approximately 2 years
Secondary	Objective Response Rate (ORR) per BICR and Investigator assessment of IDE196 + Crizotinib compared to investigator's choice of treatment	ORR per RECIST 1.1	Approximately 2 years
Secondary	Duration of Response (DOR) per BICR and Investigator assessment of IDE196 + Crizotinib compared to investigator's choice of treatment	DOR per RECIST 1.1	Approximately 2 years
Secondary	Change from baseline over time and between treatment arms in EORTC QLQ-C30	Global health status and quality of life will be assessed using the EORTC QLQ-C30 questionnaire. 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 quality of life. A positive change indicates improvement.	Approximately 2 years
Secondary	Change from baseline over time and between treatment arms in EuroQoL (EQ)-5D-5L scores	General health status will be assessed using the EQ-5D,5L questionnaire, which includes five dimensions (5D): mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 3 scoring levels, where 1 indicates a better health state (no problems) and 3 indicates a worse health state. A positive change indicates improvement.	Approximately 2 years