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

March 25, 2024 updated by: IDEAYA Biosciences

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)

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).

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Estimated)

380

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Australia
      • Adelaide, Australia
        • Not yet recruiting
        • Queen Elizabeth Hospital
    • New South Wales
      • Sydney, New South Wales, Australia, 2145
    • Queensland
      • Brisbane, Queensland, Australia, 4102
    • Victoria
      • Melbourne, Victoria, Australia, 3168
        • Recruiting
        • Alfred Health
    • Western Australia
  • Belgium
  • Canada
    • Alberta
      • Edmonton, Alberta, Canada, T6G 1Z2
        • Not yet recruiting
        • Cross Cancer Institute, University of Alberta
        • Contact:
    • Ontario
      • Toronto, Ontario, Canada, M5G 2M9
        • Recruiting
        • Princess Margaret Cancer Centre
        • Contact:
    • Quebec
  • France
  • Germany
      • Berlin, Germany, 12203
        • Not yet recruiting
        • Charité - Universitätsmedizin Berlin
        • Contact:
    • Baden- Württemberg
    • North Rhine-Westphalia
      • Essen, North Rhine-Westphalia, Germany, 45147
        • Not yet recruiting
        • Universitatsklinikum Essen (Aor)
        • Contact:
      • Köln, North Rhine-Westphalia, Germany, 50937
    • Saxony
      • Dresden, Saxony, Germany, 1307
        • Not yet recruiting
        • Universitatsklinikum Carl Gustav Carus Dresden
        • Contact:
  • Israel
  • Italy
  • Netherlands
      • Leiden, Netherlands, 2333 ZA
        • Not yet recruiting
        • LUMC (Leids Universitair Medisch Centrum)
        • Contact:
  • Poland
      • Gdańsk, Poland, 80-214
        • Not yet recruiting
        • Ośrodek Badań Klinicznych Wczesnych Faz, Uniwersyteckie Centrum Kliniczne w Gdańsku
        • Contact:
      • Warsaw, Poland, 02-781
        • Not yet recruiting
        • Narodowy Instytut Onkologii im. Marii Skłodowskiej-Curie Państwowy Instytut Badawczy
        • Contact:
  • Spain
      • L'Hospitalet de Llobregat, Spain, 8908
      • Madrid, Spain, 28046
        • Not yet recruiting
        • Hospital Universitario La Paz
        • Contact:
      • Santiago de Compostela, Spain, 15706
        • Not yet recruiting
        • Hospital Clinico Universitario de Santiago de Compostela
        • Contact:
      • Sevilla, Spain, 41009
      • Valencia, Spain, 46014
        • Not yet recruiting
        • Hospital General Universitario Valencia
        • Contact:
        • Contact:
  • Switzerland
      • Zuerich, Switzerland, 8058
        • Recruiting
        • Dermatologische Klinik, USZ Flughafen Geschoss 7 - Klinische Forschung
        • Contact:
  • United Kingdom
      • Glasgow, United Kingdom, G12 0YN
        • Not yet recruiting
        • The Beatson West of Scotland Cancer Centre
        • Contact:
      • Northwood, United Kingdom, HA6 2RN
        • Not yet recruiting
        • Mount Vernon Cancer Centre East & North Herts NHS Trust
      • Wirral, United Kingdom, CH63 4JY
        • Not yet recruiting
        • The Clatterbridge Cancer Centre NHS Foundation Trust
        • Contact:
  • United States
    • Arizona
      • Scottsdale, Arizona, United States, 85258
        • Recruiting
        • Honor Health
        • Contact:
        • Contact:
          • Phone Number: 833-354-6667
    • California
      • La Jolla, California, United States, 92093
      • Los Angeles, California, United States, 90024
      • Los Angeles, California, United States, 90025
      • San Francisco, California, United States, 94143
      • San Francisco, California, United States, 94115
    • Colorado
      • Aurora, Colorado, United States, 80045
        • Not yet recruiting
        • University of Colorado Cancer Center
      • Denver, Colorado, United States, 80218
    • Florida
      • Miami, Florida, United States, 33136
      • Tampa, Florida, United States, 33612
        • Not yet recruiting
        • Moffitt Cancer Center
    • Georgia
      • Atlanta, Georgia, United States, 30342
    • Iowa
      • Iowa City, Iowa, United States, 52242
        • Recruiting
        • University of Iowa
        • Contact:
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Recruiting
        • Massachusetts General Hospital
        • Contact:
      • Boston, Massachusetts, United States, 02215
    • Michigan
      • Grand Rapids, Michigan, United States, 49546
        • Recruiting
        • The Cancer and Hematology Centers
        • Contact:
        • Contact:
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Not yet recruiting
        • Mayo Clinic
    • Missouri
      • Saint Louis, Missouri, United States, 63110
        • Not yet recruiting
        • Washington University School of Medicine
    • New York
      • Buffalo, New York, United States, 14263
      • Manhasset, New York, United States, 11030
      • New York, New York, United States, 10065
        • Recruiting
        • Memorial Sloan Kettering Cancer Center
        • Contact:
        • Contact:
    • North Carolina
      • Durham, North Carolina, United States, 27710
    • Ohio
      • Cincinnati, Ohio, United States, 45267
        • Recruiting
        • University of Cincinnati
        • Contact:
      • Cleveland, Ohio, United States, 44195
        • Recruiting
        • The Cleveland Clinic Foundation
        • Contact:
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19107
      • Pittsburgh, Pennsylvania, United States, 15232
        • Not yet recruiting
        • University of Pittsburgh Medical Center
        • Contact:
        • Contact:
    • Tennessee
      • Nashville, Tennessee, United States, 37203
        • Recruiting
        • SCRI- Tennessee Oncology
        • Contact:
          • SCRI Front Desk
          • Phone Number: 844-482-4812
    • Texas
      • Dallas, Texas, United States, 75390
      • Houston, Texas, United States, 77030
        • Recruiting
        • MD Anderson Cancer Center
        • Contact:
      • Houston, Texas, United States, 77030
        • Not yet recruiting
        • Houston Methodist Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Phase 2a Dose Optimization of IDE196 + crizotinib
Multiple doses of IDE196 will be tested in combination with fixed dose of crizotinib to identify the optimal combination dose.
Drug: IDE196
Dosed orally, twice daily
Other Names:
  • Darovasertib
Drug: Crizotinib
Dosed orally, twice daily
Other Names:
  • XALKORI
Experimental: Phase 2b / 3 Chosen Combination dose of IDE196 + crizotinib
Chosen combination dose of IDE196 + crizotinib will be tested in additional participants.
Drug: IDE196
Dosed orally, twice daily
Other Names:
  • Darovasertib
Drug: Crizotinib
Dosed orally, twice daily
Other Names:
  • XALKORI
Active Comparator: Phase 2a / 2b / 3 Comparator Arm
Participants will receive investigator's choice of Pembrolizumab, Ipilimumab + Nivolumab, or Dacarbazine.
Drug: Pembrolizumab
IV administration every 3 weeks
Other Names:
  • Keytruda
Drug: Ipilimumab
IV administration every 3 weeks for 4 Cycles
Other Names:
  • Yervoy
Drug: Nivolumab
IV administration every 3 Weeks for 4 Cycles, thereafter every 4 Weeks maintenance
Other Names:
  • Opdivo
Drug: Dacarbazine
IV administration every 3 Weeks
Other Names:
  • DTIC-Dome

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression-Free Survival (PFS) by blinded independent central review (BICR) of IDE196 + Crizotinib compared to investigator's choice of treatment
Time Frame: Approximately 2 years
PFS per RECIST 1.1
Approximately 2 years
Overall Survival (OS) of IDE196 + Crizotinib compared to investigator's choice of treatment
Time Frame: Approximately 4 years
OS from randomization to date of death due to any cause
Approximately 4 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Safety of IDE196 + Crizotinib: Incidence of Adverse Events
Time Frame: Approximately 2 years
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
Phase 2a: Dose exposure response of IDE196
Time Frame: Approximately 5 months
Dose-exposure-response of IDE196 as measured by concentration of IDE196 in plasma
Approximately 5 months
Phase 2a: Dose exposure response of Crizotinib
Time Frame: Approximately 5 months
Dose-exposure-response of Crizotinib as measured by concentration of Crizotinib in plasma
Approximately 5 months
Progression-Free Survival (PFS) per Investigator of IDE196 + Crizotinib compared to investigator's choice of treatment
Time Frame: Approximately 2 years
PFS per RECIST 1.1
Approximately 2 years
Objective Response Rate (ORR) per BICR and Investigator assessment of IDE196 + Crizotinib compared to investigator's choice of treatment
Time Frame: Approximately 2 years
ORR per RECIST 1.1
Approximately 2 years
Duration of Response (DOR) per BICR and Investigator assessment of IDE196 + Crizotinib compared to investigator's choice of treatment
Time Frame: Approximately 2 years
DOR per RECIST 1.1
Approximately 2 years
Change from baseline over time and between treatment arms in EORTC QLQ-C30
Time Frame: Approximately 2 years
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
Change from baseline over time and between treatment arms in EuroQoL (EQ)-5D-5L scores
Time Frame: Approximately 2 years
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

IDEAYA Biosciences

Investigators

  • Study Director: Darrin Beaupre, MD, Ph.D, IDEAYA Biosciences

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 31, 2023

Primary Completion (Estimated)

January 15, 2027

Study Completion (Estimated)

January 15, 2028

Study Registration Dates

First Submitted

July 12, 2023

First Submitted That Met QC Criteria

August 3, 2023

First Posted (Actual)

August 14, 2023

Study Record Updates

Last Update Posted (Actual)

March 27, 2024

Last Update Submitted That Met QC Criteria

March 25, 2024

Last Verified

February 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IDE196-002

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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