xml: <clinical_study>
    <!-- This xml conforms to an XML Schema at:
      https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
    <required_header>
      <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
      <link_text>Link to the current ClinicalTrials.gov record.</link_text>
      <url>https://clinicaltrials.gov/ct2/show/NCT05987332</url>
    </required_header>
    <id_info>
      <org_study_id>IDE196-002</org_study_id>
      <nct_id>NCT05987332</nct_id>
    </id_info>
    <brief_title>IDE196 (Darovasertib) in Combination With Crizotinib as First-line Therapy in Metastatic Uveal Melanoma</brief_title>
    <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)</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>IDEAYA Biosciences</agency>
        <agency_class>Industry</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>IDEAYA Biosciences</source>
    <oversight_info>
      <has_dmc>Yes</has_dmc>
      <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        This is a Phase 2/3, multi-arm, multi-stage, open-label study of human leukocyte antigen&#xD;
        (HLA)-A*02:01 negative participants with metastatic uveal melanoma (MUM) who will be&#xD;
        randomized to receive either IDE196 + crizotinib or investigator's choice of treatment&#xD;
        (pembrolizumab, ipilimumab + nivolumab, or dacarbazine).&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        This study is designed as a multi-stage Phase 2 study within a Phase 3 study to evaluate the&#xD;
        safety, tolerability, pharmacokinetics, dose-exposure relationship, and anti-tumor activity&#xD;
        of IDE196 in combination with crizotinib compared to the comparator arm of investigator's&#xD;
        choice of treatment (pembrolizumab, ipilimumab + nivolumab, or dacarbazine).&#xD;
  &#xD;
        The Phase 2a dose optimization stage will evaluate two doses of IDE196 in combination with&#xD;
        crizotinib compared to the comparator arm. Participants will be randomized to the three&#xD;
        treatment arms. At the point of optimal IDE196 + crizotinib dose selection, the other dose&#xD;
        arm will be dropped with discontinuation of enrollment to that arm. Participants receiving&#xD;
        the IDE196 dose (in combination with crizotinib) that is not selected, will be offered the&#xD;
        choice to remain on the same dose or change to the chosen optimal dose.&#xD;
  &#xD;
        The optimal dose will be chosen to complete the Phase 2b portion. The Phase 2b part of the&#xD;
        study will continue to enroll the chosen combination dose of IDE196 + crizotinib compared&#xD;
        with the comparator arm. Participants will be randomized to the two treatment arms.&#xD;
  &#xD;
        The Phase 3 part of the study will continue to enroll the chosen combination dose of IDE196 +&#xD;
        crizotinib compared with the comparator arm. Participants will be randomized to the two&#xD;
        treatment arms.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Recruiting</overall_status>
    <start_date type="Anticipated">August 31, 2023</start_date>
    <completion_date type="Anticipated">January 15, 2028</completion_date>
    <primary_completion_date type="Anticipated">January 15, 2027</primary_completion_date>
    <phase>Phase 2/Phase 3</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>Randomized</allocation>
      <intervention_model>Sequential Assignment</intervention_model>
      <primary_purpose>Treatment</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Progression-Free Survival (PFS) by blinded independent central review (BICR) of IDE196 + Crizotinib compared to investigator's choice of treatment</measure>
      <time_frame>Approximately 2 years</time_frame>
      <description>PFS per RECIST 1.1</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Overall Survival (OS) of IDE196 + Crizotinib compared to investigator's choice of treatment</measure>
      <time_frame>Approximately 4 years</time_frame>
      <description>OS from randomization to date of death due to any cause</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Safety of IDE196 + Crizotinib: Incidence of Adverse Events</measure>
      <time_frame>Approximately 2 years</time_frame>
      <description>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</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Phase 2a: Dose exposure response of IDE196</measure>
      <time_frame>Approximately 5 months</time_frame>
      <description>Dose-exposure-response of IDE196 as measured by concentration of IDE196 in plasma</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Phase 2a: Dose exposure response of Crizotinib</measure>
      <time_frame>Approximately 5 months</time_frame>
      <description>Dose-exposure-response of Crizotinib as measured by concentration of Crizotinib in plasma</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Progression-Free Survival (PFS) per Investigator of IDE196 + Crizotinib compared to investigator's choice of treatment</measure>
      <time_frame>Approximately 2 years</time_frame>
      <description>PFS per RECIST 1.1</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Objective Response Rate (ORR) per BICR and Investigator assessment of IDE196 + Crizotinib compared to investigator's choice of treatment</measure>
      <time_frame>Approximately 2 years</time_frame>
      <description>ORR per RECIST 1.1</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Duration of Response (DOR) per BICR and Investigator assessment of IDE196 + Crizotinib compared to investigator's choice of treatment</measure>
      <time_frame>Approximately 2 years</time_frame>
      <description>DOR per RECIST 1.1</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change from baseline over time and between treatment arms in EORTC QLQ-C30</measure>
      <time_frame>Approximately 2 years</time_frame>
      <description>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.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change from baseline over time and between treatment arms in EuroQoL (EQ)-5D-5L scores</measure>
      <time_frame>Approximately 2 years</time_frame>
      <description>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.</description>
    </secondary_outcome>
    <number_of_arms>3</number_of_arms>
    <enrollment type="Anticipated">380</enrollment>
    <condition>Metastatic Uveal Melanoma</condition>
    <arm_group>
      <arm_group_label>Phase 2a Dose Optimization of IDE196 + crizotinib</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Multiple doses of IDE196 will be tested in combination with fixed dose of crizotinib to identify the optimal combination dose.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Phase 2b / 3 Chosen Combination dose of IDE196 + crizotinib</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Chosen combination dose of IDE196 + crizotinib will be tested in additional participants.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Phase 2a / 2b / 3 Comparator Arm</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>Participants will receive investigator's choice of Pembrolizumab, Ipilimumab + Nivolumab, or Dacarbazine.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>IDE196</intervention_name>
      <description>Dosed orally, twice daily</description>
      <arm_group_label>Phase 2a Dose Optimization of IDE196 + crizotinib</arm_group_label>
      <arm_group_label>Phase 2b / 3 Chosen Combination dose of IDE196 + crizotinib</arm_group_label>
      <other_name>Darovasertib</other_name>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Crizotinib</intervention_name>
      <description>Dosed orally, twice daily</description>
      <arm_group_label>Phase 2a Dose Optimization of IDE196 + crizotinib</arm_group_label>
      <arm_group_label>Phase 2b / 3 Chosen Combination dose of IDE196 + crizotinib</arm_group_label>
      <other_name>XALKORI</other_name>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Pembrolizumab</intervention_name>
      <description>IV administration every 3 weeks</description>
      <arm_group_label>Phase 2a / 2b / 3 Comparator Arm</arm_group_label>
      <other_name>Keytruda</other_name>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Ipilimumab</intervention_name>
      <description>IV administration every 3 weeks for 4 Cycles</description>
      <arm_group_label>Phase 2a / 2b / 3 Comparator Arm</arm_group_label>
      <other_name>Yervoy</other_name>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Nivolumab</intervention_name>
      <description>IV administration every 3 Weeks for 4 Cycles, thereafter every 4 Weeks maintenance</description>
      <arm_group_label>Phase 2a / 2b / 3 Comparator Arm</arm_group_label>
      <other_name>Opdivo</other_name>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Dacarbazine</intervention_name>
      <description>IV administration every 3 Weeks</description>
      <arm_group_label>Phase 2a / 2b / 3 Comparator Arm</arm_group_label>
      <other_name>DTIC-Dome</other_name>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Histological or cytological confirmed Metastatic Uveal Melanoma&#xD;
  &#xD;
            -  HLA-A*02:01 negative&#xD;
  &#xD;
            -  No prior systemic therapy in the metastatic or advanced setting, regional or&#xD;
               liver-directed therapy, ablations or surgical resection of oligometastatic disease, or&#xD;
               neoadjuvant or adjuvant therapy is allowed&#xD;
  &#xD;
            -  Measurable disease per RECIST 1.1&#xD;
  &#xD;
            -  Able to be safely administered and absorb study therapy&#xD;
  &#xD;
            -  ECOG performance status 0 or 1&#xD;
  &#xD;
            -  Life expectancy of ≥3 months&#xD;
  &#xD;
            -  Adequate organ function&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Previous treatment with a PKC inhibitor (including prior treatment with IDE196), an&#xD;
               inhibitor directly targeting MET, or an inhibitor directly targeting GNAQ/11&#xD;
  &#xD;
            -  Concurrent malignant disease&#xD;
  &#xD;
            -  AEs from prior anti-cancer therapy that have not resolved to Grade ≤1&#xD;
  &#xD;
            -  Symptomatic or untreated central nervous system (CNS) metastases, or CNS metastases&#xD;
               that require corticosteroids&#xD;
  &#xD;
            -  Active HIV infection or Hep B/C&#xD;
  &#xD;
            -  Active adrenal insufficiency, active colitis, or active inflammatory bowel disease&#xD;
  &#xD;
            -  History of interstitial lung disease, active pneumonitis, or history of pneumonitis&#xD;
  &#xD;
            -  Active infection requiring systemic antibiotic therapy&#xD;
  &#xD;
            -  Use of hematopoietic colony-stimulating factors (CSF) prior to start of study drug&#xD;
  &#xD;
            -  Females who are pregnant or breastfeeding&#xD;
  &#xD;
            -  History of severe hypersensitivity reactions (eg, anaphylaxis) to other biologic drugs&#xD;
               or monoclonal antibodies&#xD;
  &#xD;
            -  Contraindication for treatment with investigator's choice therapies as per applicable&#xD;
               labelling&#xD;
  &#xD;
            -  Has any other condition that may increase the risk associated with study participation&#xD;
               or may interfere with the interpretation of study results and, in the opinion of the&#xD;
               investigator, would make the participant inappropriate for entry into the study&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>N/A</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Matthew Maurer, MD</last_name>
      <role>Study Director</role>
      <affiliation>IDEAYA Biosciences</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>IDEAYA Clinical Trials</last_name>
      <phone>1 650-534-3616</phone>
      <email>IDEAYAClinicalTrials@ideayabio.com</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Matthew Maurer, MD</last_name>
      <email>mmaurer@ideayabio.com</email>
    </overall_contact_backup>
    <location>
      <facility>
        <name>The Cancer and Hematology Centers</name>
        <address>
          <city>Grand Rapids</city>
          <state>Michigan</state>
          <zip>49546</zip>
          <country>United States</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>The Cancer and Hematology Centers</last_name>
        <phone>616-954-5550</phone>
        <email>ClinicalTrials@chcwm.com</email>
      </contact>
      <contact_backup>
        <last_name>Jessica Miller, RN</last_name>
        <phone>616-954-5550</phone>
        <phone_ext>1651</phone_ext>
        <email>Jmiller@chcwm.com</email>
      </contact_backup>
    </location>
    <location_countries>
      <country>United States</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>July 12, 2023</study_first_submitted>
    <study_first_submitted_qc>August 3, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 14, 2023</study_first_posted>
    <last_update_submitted>August 14, 2023</last_update_submitted>
    <last_update_submitted_qc>August 14, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 16, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>IDE196</keyword>
    <keyword>Darovasertib</keyword>
    <keyword>Protein Kinase C</keyword>
    <keyword>Metastatic Uveal Melanoma</keyword>
    <keyword>Melanoma</keyword>
    <keyword>Ocular Oncology</keyword>
    <keyword>Ophthalmology</keyword>
    <keyword>Crizotinib</keyword>
    <keyword>Ocular melanoma</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Melanoma</mesh_term>
      <mesh_term>Uveal Neoplasms</mesh_term>
    </condition_browse>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Pembrolizumab</mesh_term>
      <mesh_term>Nivolumab</mesh_term>
      <mesh_term>Ipilimumab</mesh_term>
      <mesh_term>Dacarbazine</mesh_term>
      <mesh_term>Crizotinib</mesh_term>
    </intervention_browse>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: download date: ClinicalTrials.gov processed this data on September 20, 2023
  link text: Link to the current ClinicalTrials.gov record.
  url: https://clinicaltrials.gov/ct2/show/NCT05987332
  org study id: IDE196-002
  nct id: NCT05987332
  lead sponsor: 
  has dmc: Yes
  is fda regulated drug: Yes
  is fda regulated device: No
  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).
  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.
  allocation: Randomized
  intervention model: Sequential Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: 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
  description: PFS per RECIST 1.1
  measure: Overall Survival (OS) of IDE196 + Crizotinib compared to investigator's choice of treatment
  time frame: Approximately 4 years
  description: OS from randomization to date of death due to any cause
  measure: Safety of IDE196 + Crizotinib: Incidence of Adverse Events
  time frame: Approximately 2 years
  description: 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
  measure: Phase 2a: Dose exposure response of IDE196
  time frame: Approximately 5 months
  description: Dose-exposure-response of IDE196 as measured by concentration of IDE196 in plasma
  measure: Phase 2a: Dose exposure response of Crizotinib
  time frame: Approximately 5 months
  description: Dose-exposure-response of Crizotinib as measured by concentration of Crizotinib in plasma
  measure: Progression-Free Survival (PFS) per Investigator of IDE196 + Crizotinib compared to investigator's choice of treatment
  time frame: Approximately 2 years
  description: PFS per RECIST 1.1
  measure: Objective Response Rate (ORR) per BICR and Investigator assessment of IDE196 + Crizotinib compared to investigator's choice of treatment
  time frame: Approximately 2 years
  description: ORR per RECIST 1.1
  measure: Duration of Response (DOR) per BICR and Investigator assessment of IDE196 + Crizotinib compared to investigator's choice of treatment
  time frame: Approximately 2 years
  description: DOR per RECIST 1.1
  measure: Change from baseline over time and between treatment arms in EORTC QLQ-C30
  time frame: Approximately 2 years
  description: 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.
  measure: Change from baseline over time and between treatment arms in EuroQoL (EQ)-5D-5L scores
  time frame: Approximately 2 years
  description: 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.
  arm group label: Phase 2a Dose Optimization of IDE196 + crizotinib
  arm group type: Experimental
  description: Multiple doses of IDE196 will be tested in combination with fixed dose of crizotinib to identify the optimal combination dose.
  arm group label: Phase 2b / 3 Chosen Combination dose of IDE196 + crizotinib
  arm group type: Experimental
  description: Chosen combination dose of IDE196 + crizotinib will be tested in additional participants.
  arm group label: Phase 2a / 2b / 3 Comparator Arm
  arm group type: Active Comparator
  description: Participants will receive investigator's choice of Pembrolizumab, Ipilimumab + Nivolumab, or Dacarbazine.
  intervention type: Drug
  intervention name: IDE196
  description: Dosed orally, twice daily
  arm group label: Phase 2a Dose Optimization of IDE196 + crizotinib
  arm group label: Phase 2b / 3 Chosen Combination dose of IDE196 + crizotinib
  other name: Darovasertib
  intervention type: Drug
  intervention name: Crizotinib
  description: Dosed orally, twice daily
  arm group label: Phase 2a Dose Optimization of IDE196 + crizotinib
  arm group label: Phase 2b / 3 Chosen Combination dose of IDE196 + crizotinib
  other name: XALKORI
  intervention type: Drug
  intervention name: Pembrolizumab
  description: IV administration every 3 weeks
  arm group label: Phase 2a / 2b / 3 Comparator Arm
  other name: Keytruda
  intervention type: Drug
  intervention name: Ipilimumab
  description: IV administration every 3 weeks for 4 Cycles
  arm group label: Phase 2a / 2b / 3 Comparator Arm
  other name: Yervoy
  intervention type: Drug
  intervention name: Nivolumab
  description: IV administration every 3 Weeks for 4 Cycles, thereafter every 4 Weeks maintenance
  arm group label: Phase 2a / 2b / 3 Comparator Arm
  other name: Opdivo
  intervention type: Drug
  intervention name: Dacarbazine
  description: IV administration every 3 Weeks
  arm group label: Phase 2a / 2b / 3 Comparator Arm
  other name: DTIC-Dome
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Matthew Maurer, MD
  role: Study Director
  affiliation: IDEAYA Biosciences
  last name: IDEAYA Clinical Trials
  phone: 1 650-534-3616
  email: IDEAYAClinicalTrials@ideayabio.com
  last name: Matthew Maurer, MD
  email: mmaurer@ideayabio.com
  facility: 
  status: Recruiting
  contact: 
  contact backup: 
  country: United States
  responsible party type: Sponsor
  mesh term: Melanoma
  mesh term: Uveal Neoplasms
  mesh term: Pembrolizumab
  mesh term: Nivolumab
  mesh term: Ipilimumab
  mesh term: Dacarbazine
  mesh term: Crizotinib