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

NCT05987332 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: IDE196-002
• Study Type: interventional
• Target: 420
• Locations: 13 countries
• Sites: 68

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).

Conditions

Metastatic Uveal Melanoma

Keywords

IDE196; Darovasertib; Protein Kinase C; Metastatic Uveal Melanoma; Melanoma; Ocular Oncology; Ophthalmology; Crizotinib; Ocular melanoma

Outcome Measures

Primary Outcomes (3)

• Phase 2a: To determine the optimal dose of IDE196 + Crizotinib combination for Phase 2B and Phase 3 by evaluating the following:

  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.

  Approximately 5 months

• Phase 2 Progression-Free Survival (PFS)

  by blinded independent central review (BICR) of IDE196 + Crizotinib compared to investigator's choice of treatment per RECIST v1.1

  Approximately 2 years

• Phase 3 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 Outcomes (11)

• Safety of IDE196 + Crizotinib: Incidence of Adverse Events

  Approximately 2 years

• Phase 2a: Dose-exposure-response of IDE196 as measured by correlating the concentration of IDE196 in plasma with safety and efficacy.

  Approximately 5 months

• Phase 2a: Dose-exposure-response of Crizotinib measured by correlating the concentration of Crizotinib in plasma with safety and efficacy.

  Approximately 5 months

• Phase 2b + 3: Progression-Free Survival (PFS) per Investigator Assessment of IDE196 + Crizotinib compared to investigator's choice of treatment .

  Approximately 2 years

• Objective Response Rate (ORR) per BICR and Investigator assessment of IDE196 + Crizotinib compared to investigator's choice of treatment

  Approximately 2 years

Study Arms (3)

Phase 2a Dose Optimization of IDE196 + crizotinib

EXPERIMENTAL

Multiple doses of IDE196 will be tested in combination with fixed dose of crizotinib to identify the optimal combination dose.

Drug: IDE196; Drug: Crizotinib

Phase 2b / 3 Chosen Combination dose of IDE196 + crizotinib

EXPERIMENTAL

Chosen combination dose of IDE196 + crizotinib will be tested in additional participants.

Drug: IDE196; Drug: Crizotinib

Phase 2a / 2b / 3 Comparator Arm

ACTIVE COMPARATOR

Participants will receive investigator's choice of Pembrolizumab, Ipilimumab + Nivolumab, or Dacarbazine.

Drug: Pembrolizumab; Drug: Ipilimumab; Drug: Nivolumab; Drug: Dacarbazine

Interventions

IDE196 DRUG

Dosed orally, twice daily

Also known as: Darovasertib

Phase 2a Dose Optimization of IDE196 + crizotinib; Phase 2b / 3 Chosen Combination dose of IDE196 + crizotinib

Crizotinib DRUG

Dosed orally, twice daily

Also known as: XALKORI

Phase 2a Dose Optimization of IDE196 + crizotinib; Phase 2b / 3 Chosen Combination dose of IDE196 + crizotinib

Pembrolizumab DRUG

IV administration every 3 weeks

Also known as: Keytruda

Phase 2a / 2b / 3 Comparator Arm

Ipilimumab DRUG

IV administration every 3 weeks for 4 Cycles

Also known as: Yervoy

Phase 2a / 2b / 3 Comparator Arm

Nivolumab DRUG

IV administration every 3 Weeks for 4 Cycles, thereafter every 4 Weeks maintenance

Also known as: Opdivo

Phase 2a / 2b / 3 Comparator Arm

Dacarbazine DRUG

IV administration every 3 Weeks

Also known as: DTIC-Dome

Phase 2a / 2b / 3 Comparator Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• IDEAYA Biosciences: lead

Study Sites (68)

Honor Health

Scottsdale, Arizona, 85258, United States

Location

Moores Cancer Center

La Jolla, California, 92093, United States

Location

UCLA Medical Center

Los Angeles, California, 90024, United States

Location

The Angeles Clinic and Research Institute

Los Angeles, California, 90025, United States

Location

California Pacific Medical Center (CPMC)

San Francisco, California, 94115, United States

Location

University of California San Francisco

San Francisco, California, 94143, United States

Location

University of Colorado Cancer Center

Aurora, Colorado, 80045, United States

Location

SCRI at HealthONE

Denver, Colorado, 80218, United States

Location

University of Miami Sylvester Comprehensive Cancer Center

Miami, Florida, 33136, United States

Location

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

Northside Hospital Atlanta

Atlanta, Georgia, 30342, United States

Location

University of Iowa

Iowa City, Iowa, 52242, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

The Cancer and Hematology Centers

Grand Rapids, Michigan, 49546, United States

Location

Minnesota Oncology Hematology, P.A.

Burnsville, Minnesota, 55337, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

Northwell Health

Manhasset, New York, 11030, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Duke University Health System

Durham, North Carolina, 27710, United States

Location

University of Cincinnati

Cincinnati, Ohio, 45267, United States

Location

The Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States

Location

Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15232, United States

Location

SCRI Oncology Partners

Nashville, Tennessee, 37203, United States

Location

Texas Oncology- DFW

Dallas, Texas, 75246, United States

Location

UT Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

Houston Methodist Cancer Center

Houston, Texas, 77030, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Westmead Hospital

Sydney, New South Wales, 2145, Australia

Location

Princess Alexander Hospital

Brisbane, Queensland, 4102, Australia

Location

Peter MacCallum Cancer Centre

Melbourne, Victoria, 3000, Australia

Location

Alfred Health

Melbourne, Victoria, 3168, Australia

Location

Sir Charles Gairdner Hospital

Perth, Washington, 6009, Australia

Location

Queen Elizabeth Hospital

Adelaide, Australia

Location

Cliniques Universitaires Saint Luc

Brussels, 1200, Belgium

Location

Algemene Medische Oncologie UZ

Leuven, 3000, Belgium

Location

Cross Cancer Institute, University of Alberta

Edmonton, Alberta, T6G 1Z2, Canada

Location

BC Cancer Agency

Vancouver, British Columbia, V5Z4C2, Canada

Location

Princess Margaret Cancer Centre

Toronto, Ontario, M5G 2M9, Canada

Location

Centre Hospitalier de l'Universite de Montreal- CHUM

Montreal, Quebec, H2X 0C1, Canada

Location

The Leon Berard Center

Lyon, France

Location

Institut Curie

Paris, 75005, France

Location

NCT Heidelberg

Heidelberg, Baden-Wurttemberg, 69120, Germany

Location

Universitätsklinikum Köln

Cologne, North Rhine-Westphalia, 50937, Germany

Location

Universitätsklinikum Essen (AöR)

Essen, North Rhine-Westphalia, 45147, Germany

Location

Universitätsklinikum Carl Gustav Carus Dresden

Dresden, Saxony, 1307, Germany

Location

Charité - Universitätsmedizin Berlin

Berlin, 12203, Germany

Location

Hadassah Medical Center

Jerusalem, 91120, Israel

Location

Sheba Medical Center

Ramat Gan, 52621, Israel

Location

Fondazione IRCCS Istituto Nazionale dei Tumori

Milan, 20133, Italy

Location

Istituto Nazionale dei Tumori Fondazione Pascale

Naples, 80131, Italy

Location

Fondazione Policlinico Gemelli IRCCS

Roma, 00168, Italy

Location

AOUS Policlinico Le Scotte

Siena, 53100, Italy

Location

LUMC (Leids Universitair Medisch Centrum)

Leiden, 2333 ZA, Netherlands

Location

Ośrodek Badań Klinicznych Wczesnych Faz, Uniwersyteckie Centrum Kliniczne w Gdańsku

Gdansk, 80-214, Poland

Location

Narodowy Instytut Onkologii im. Marii Skłodowskiej-Curie Państwowy Instytut Badawczy

Warsaw, 02-781, Poland

Location

Catalan Institute of Oncology

L'Hospitalet de Llobregat, 8908, Spain

Location

Hospital Universitario La Paz

Madrid, 28046, Spain

Location

Hospital Clínico Universitario de Santiago de Compostela

Santiago de Compostela, 15706, Spain

Location

Hospital Universitario Virgen Macarena

Seville, 41009, Spain

Location

Hospital General Universitario Valencia

Valencia, 46014, Spain

Location

Dermatologische Klinik, USZ Flughafen Geschoss 7 - Klinische Forschung

Zurich, 8058, Switzerland

Location

The Beatson West of Scotland Cancer Centre

Glasgow, G12 0YN, United Kingdom

Location

The Clatterbridge Cancer Centre NHS Foundation Trust

Metropolitan Borough of Wirral, CH63 4JY, United Kingdom

Location

Mount Vernon Cancer Centre East & North Herts NHS Trust

Northwood, HA6 2RN, United Kingdom

Location

MeSH Terms

Conditions

Uveal Melanoma; Melanoma

Interventions

Crizotinib; pembrolizumab; Ipilimumab; Nivolumab; Dacarbazine

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Uveal Neoplasms; Eye Neoplasms; Neoplasms by Site; Eye Diseases; Uveal Diseases; Skin Neoplasms; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Aminopyridines; Pyridines; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Triazenes; Organic Chemicals; Imidazoles; Azoles

Study Officials

• Hetal Patel, MD, MSHS, CHCQM

  IDEAYA Biosciences

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 12, 2023
• First Posted: August 14, 2023
• Study Start: October 31, 2023
• Primary Completion (Estimated): January 15, 2027
• Study Completion (Estimated): January 15, 2028
• Last Updated: February 17, 2026

Record last verified: 2026-02

Locations

US (31); NL (1); PL (2); CA (4); IL (2); BE (2); IT (4); AU (6); FR (2); GB (3); DE (5); CH (1); ES (5)