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/NCT06026410</url>
    </required_header>
    <id_info>
      <org_study_id>KO-2806-001</org_study_id>
      <nct_id>NCT06026410</nct_id>
    </id_info>
    <brief_title>KO-2806 Monotherapy and Combination Therapies in Advanced Solid Tumors</brief_title>
    <acronym>FIT-001</acronym>
    <official_title>Phase 1, First-in-Human, Multicenter, Open-Label Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Antitumor Activity of KO-2806 When Administered as Monotherapy and in Combination Therapy in Adult Patients With Advanced Solid Tumors</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Kura Oncology, Inc.</agency>
        <agency_class>Industry</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Kura Oncology, Inc.</source>
    <oversight_info>
      <has_dmc>No</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 first-in-human (FIH) dose-escalation and dose-validation/expansion study will assess&#xD;
        KO-2806, a farnesyl transferase inhibitor (FTI), as a monotherapy and in combination, in&#xD;
        adult patients with advanced solid tumors.&#xD;
      </textblock>
    </brief_summary>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">September 2023</start_date>
    <completion_date type="Anticipated">April 2027</completion_date>
    <primary_completion_date type="Anticipated">January 2027</primary_completion_date>
    <phase>Phase 1</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>Non-Randomized</allocation>
      <intervention_model>Sequential Assignment</intervention_model>
      <primary_purpose>Treatment</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Rate of dose-limiting toxicities (DLTs)</measure>
      <time_frame>DLTs will be evaluated during the first 28 days of KO-2806 treatment (dose escalation)</time_frame>
    </primary_outcome>
    <primary_outcome>
      <measure>Descriptive statistics of adverse events</measure>
      <time_frame>First dose of KO-2806 up to and including 28 days after last dose of KO-2806, or if the patient is lost to follow-up, whichever comes first (dose escalation)</time_frame>
      <description>NCI-CTCAE v5.0</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Overall Response Rate (ORR)</measure>
      <time_frame>Up to an estimated period of 24 months (dose expansion)</time_frame>
      <description>Assessed per RECIST v1.1</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Rate of dose-limiting toxicities (DLTs)</measure>
      <time_frame>DLTs will be evaluated during the first 28 days of KO-2806 treatment (dose expansion)</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Descriptive statistics of adverse events</measure>
      <time_frame>First dose of KO-2806 up to and including 28 days after last dose of KO-2806, or if the patient is lost to follow-up, whichever comes first (dose expansion)</time_frame>
      <description>NCI-CTCAE v5.0</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Objective Response Rate (ORR)</measure>
      <time_frame>Up to an estimated period of 24 months</time_frame>
      <description>Assessed per RECIST v1.1</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Disease control rate (DCR)</measure>
      <time_frame>Up to an estimated period of 24 months</time_frame>
      <description>Assessed per RECIST v1.1</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Duration of response (DoR)</measure>
      <time_frame>Up to an estimated period of 24 months</time_frame>
      <description>Assessed per RECIST v1.1</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Progression-Free Survival (PFS)</measure>
      <time_frame>Up to an estimated period of 24 months</time_frame>
      <description>Assessed per RECIST v1.1</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Overall Survival (OS)</measure>
      <time_frame>Up to an estimated period of 24 months</time_frame>
      <description>Assessed per RECIST v1.1</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>AUClast</measure>
      <time_frame>Cycle 1. Each cycle is 28 days. (Dose escalation and dose expansion).</time_frame>
      <description>Area under the curve from time zero to last measurable concentration for KO-2806 (in the absence and presence of food) and combination agent.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>AUC0-inf</measure>
      <time_frame>Cycle 1. Each cycle is 28 days. (Dose escalation and dose expansion).</time_frame>
      <description>Area under the curve from time zero to infinity post administration for KO-2806 (in the absence and presence of food) and combination agent</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Cmax</measure>
      <time_frame>Cycle 1. Each cycle is 28 days. (Dose escalation and dose expansion).</time_frame>
      <description>Maximum plasma concentration (Cmax) of KO-2806 (in the absence and presence of food) and the combination agent</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Tmax</measure>
      <time_frame>Cycle 1. Each cycle is 28 days. (Dose escalation and dose expansion).</time_frame>
      <description>Time to maximal concentration (Tmax) of KO-2806 (in the absence and presence of food) and the combination agent</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Estimated terminal elimination rate constant (λz)</measure>
      <time_frame>Cycle 1. Each cycle is 28 days. (Dose escalation and dose expansion).</time_frame>
      <description>Estimated terminal elimination rate constant of KO-2806 and the combination agent</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>t1/2</measure>
      <time_frame>Cycle 1. Each cycle is 28 days. (Dose escalation and dose expansion).</time_frame>
      <description>Half-life (t1/2) of KO-2806 (in the absence and presence of food) and the combination agent</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>CL/F</measure>
      <time_frame>Cycle 1. Each cycle is 28 days. (Dose escalation and dose expansion).</time_frame>
      <description>Oral clearance (CL/F) of KO-2806 and the combination agent</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Vd/F</measure>
      <time_frame>Cycle 1. Each cycle is 28 days. (Dose escalation and dose expansion).</time_frame>
      <description>Oral volume of distribution (Vd/F) of KO-2806 and the combination agent</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>QTcF</measure>
      <time_frame>Up to day 7 following first dose of KO-2806. Dose escalation.</time_frame>
      <description>QT interval corrected for heart rate (HR) using Fridericia's formula (QTcF) for KO-2806 monotherapy (dose escalation)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>KO-2806 plasma concentration measurements</measure>
      <time_frame>Up to day 7 following first dose of KO-2806. Dose escalation.</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Amount of KO-2806 excretion in urine</measure>
      <time_frame>Up to 24 hours following first dose of KO-2806. Dose escalation.</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>CLr of KO-2806 excretion in urine</measure>
      <time_frame>Up to 24 hours following first dose of KO-2806. Dose escalation.</time_frame>
      <description>Renal clearance of KO-2806 excretion in urine</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>t1/2 of KO-2806 excretion in urine</measure>
      <time_frame>Up to 24 hours following first dose of KO-2806. Dose escalation.</time_frame>
      <description>Half-life of KO-2806 excretion in urine</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Relative bioavailability of KO-2806 formulations</measure>
      <time_frame>Up to 24 hours following first dose of KO-2806. Dose expansion.</time_frame>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">270</enrollment>
    <condition>Solid Tumors With HRAS Alterations</condition>
    <condition>Non Small Cell Lung Cancer (NSCLC)</condition>
    <condition>Colorectal Cancer (CRC)</condition>
    <condition>Pancreatic Ductal Adenocarcinoma (PDAC)</condition>
    <condition>Clear Cell Renal Cell Carcinoma (ccRCC)</condition>
    <arm_group>
      <arm_group_label>Arm #1: RAS-altered advanced solid tumors</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Patients with advanced solid tumors and the following:&#xD;
  HRAS-mutant and/or amplified tumors (any solid tumor type)&#xD;
  HRAS overexpression (only for HNSCC tumors)&#xD;
  KRAS and/or NRAS and/or HRAS-mutant and/or amplified for NSCLC or CRC&#xD;
  KRAS-mutant and/or amplified PDAC</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Arm #2: Advanced or metastatic ccRCC</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Patients who have received at least 1 prior systemic therapy with IO-based treatment for locally advanced or metastatic RCC with predominantly clear cell subtype</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>KO-2806</intervention_name>
      <description>Oral administration</description>
      <arm_group_label>Arm #1: RAS-altered advanced solid tumors</arm_group_label>
      <arm_group_label>Arm #2: Advanced or metastatic ccRCC</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Cabozantinib</intervention_name>
      <description>Oral administration</description>
      <arm_group_label>Arm #2: Advanced or metastatic ccRCC</arm_group_label>
      <other_name>Cabometyx</other_name>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  At least 18 years of age.&#xD;
  &#xD;
            -  Histologically or cytologically confirmed advanced solid tumors&#xD;
  &#xD;
                 -  Arm #1 (Monotherapy): HRAS-mutant and/or amplified tumors (any solid tumor type);&#xD;
                    HRAS overexpression (only for HNSCC tumors); KRAS and/or NRAS, and/or HRAS-mutant&#xD;
                    and/or amplified NSCLC or CRC; KRAS-mutant and/or amplified PDAC&#xD;
  &#xD;
                 -  Arm #2 (Combination): Must have received at least 1 prior systemic therapy with&#xD;
                    IO-based treatment for locally advanced or metastatic RCC with predominantly&#xD;
                    clear cell subtype&#xD;
  &#xD;
            -  Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.&#xD;
  &#xD;
            -  Karnofsky Performance Status of 70 or higher with no clinically significant&#xD;
               deterioration over the previous 2 weeks.&#xD;
  &#xD;
            -  Acceptable liver, renal, endocrine, and hematologic function.&#xD;
  &#xD;
            -  Other protocol-defined inclusion criteria may apply.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Ongoing treatment with certain anticancer agents.&#xD;
  &#xD;
            -  Prior treatment with an FTI or HRAS inhibitor.&#xD;
  &#xD;
            -  Major surgery, other than local procedures, within 28 days prior to Cycle 1 Day 1,&#xD;
               without complete recovery.&#xD;
  &#xD;
            -  Spinal cord compression, leptomeningeal disease, or clinically active CNS metastases.&#xD;
  &#xD;
            -  Toxicity (excluding alopecia) from prior therapy that has not been completely resolved&#xD;
               to baseline at the time of consent.&#xD;
  &#xD;
            -  Active or prior documented autoimmune or inflammatory disorders within the past 5&#xD;
               years prior to Cycle 1 Day 1 (with exceptions).&#xD;
  &#xD;
            -  Active, uncontrolled bacterial, viral, or fungal infections requiring systemic&#xD;
               therapy.&#xD;
  &#xD;
            -  Inability to swallow, impairment of gastrointestinal (GI) function or GI disease that&#xD;
               may significantly alter the absorption of the trial drugs.&#xD;
  &#xD;
            -  Inadequate cardiac and/or vascular function, including receipt of treatment for&#xD;
               unstable angina, myocardial infarction, and/or cerebro-vascular attack within the&#xD;
               prior 6 months, mean QTcF ≥470 ms, or Class II or greater congestive heart failure.&#xD;
  &#xD;
            -  Other invasive malignancy within 2 years.&#xD;
  &#xD;
            -  Other protocol-defined exclusion criteria may apply.&#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_contact>
      <last_name>Clinical Operations</last_name>
      <phone>617-588-3755</phone>
      <email>KO-2806-001@kuraoncology.com</email>
    </overall_contact>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 17, 2023</study_first_submitted>
    <study_first_submitted_qc>August 30, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">September 7, 2023</study_first_posted>
    <last_update_submitted>August 30, 2023</last_update_submitted>
    <last_update_submitted_qc>August 30, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 7, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>HRAS</keyword>
    <keyword>KRAS</keyword>
    <keyword>NRAS</keyword>
    <keyword>Farnesyl transferase inhibitor (FTI)</keyword>
    <keyword>Tyrosine Kinase inhibitor (TKI)</keyword>
    <keyword>Phase 1</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Carcinoma, Renal Cell</mesh_term>
    </condition_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/NCT06026410
  org study id: KO-2806-001
  nct id: NCT06026410
  lead sponsor: 
  has dmc: No
  is fda regulated drug: Yes
  is fda regulated device: No
  This first-in-human (FIH) dose-escalation and dose-validation/expansion study will assess
        KO-2806, a farnesyl transferase inhibitor (FTI), as a monotherapy and in combination, in
        adult patients with advanced solid tumors.
  allocation: Non-Randomized
  intervention model: Sequential Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Rate of dose-limiting toxicities (DLTs)
  time frame: DLTs will be evaluated during the first 28 days of KO-2806 treatment (dose escalation)
  measure: Descriptive statistics of adverse events
  time frame: First dose of KO-2806 up to and including 28 days after last dose of KO-2806, or if the patient is lost to follow-up, whichever comes first (dose escalation)
  description: NCI-CTCAE v5.0
  measure: Overall Response Rate (ORR)
  time frame: Up to an estimated period of 24 months (dose expansion)
  description: Assessed per RECIST v1.1
  measure: Rate of dose-limiting toxicities (DLTs)
  time frame: DLTs will be evaluated during the first 28 days of KO-2806 treatment (dose expansion)
  measure: Descriptive statistics of adverse events
  time frame: First dose of KO-2806 up to and including 28 days after last dose of KO-2806, or if the patient is lost to follow-up, whichever comes first (dose expansion)
  description: NCI-CTCAE v5.0
  measure: Objective Response Rate (ORR)
  time frame: Up to an estimated period of 24 months
  description: Assessed per RECIST v1.1
  measure: Disease control rate (DCR)
  time frame: Up to an estimated period of 24 months
  description: Assessed per RECIST v1.1
  measure: Duration of response (DoR)
  time frame: Up to an estimated period of 24 months
  description: Assessed per RECIST v1.1
  measure: Progression-Free Survival (PFS)
  time frame: Up to an estimated period of 24 months
  description: Assessed per RECIST v1.1
  measure: Overall Survival (OS)
  time frame: Up to an estimated period of 24 months
  description: Assessed per RECIST v1.1
  measure: AUClast
  time frame: Cycle 1. Each cycle is 28 days. (Dose escalation and dose expansion).
  description: Area under the curve from time zero to last measurable concentration for KO-2806 (in the absence and presence of food) and combination agent.
  measure: AUC0-inf
  time frame: Cycle 1. Each cycle is 28 days. (Dose escalation and dose expansion).
  description: Area under the curve from time zero to infinity post administration for KO-2806 (in the absence and presence of food) and combination agent
  measure: Cmax
  time frame: Cycle 1. Each cycle is 28 days. (Dose escalation and dose expansion).
  description: Maximum plasma concentration (Cmax) of KO-2806 (in the absence and presence of food) and the combination agent
  measure: Tmax
  time frame: Cycle 1. Each cycle is 28 days. (Dose escalation and dose expansion).
  description: Time to maximal concentration (Tmax) of KO-2806 (in the absence and presence of food) and the combination agent
  measure: Estimated terminal elimination rate constant (λz)
  time frame: Cycle 1. Each cycle is 28 days. (Dose escalation and dose expansion).
  description: Estimated terminal elimination rate constant of KO-2806 and the combination agent
  measure: t1/2
  time frame: Cycle 1. Each cycle is 28 days. (Dose escalation and dose expansion).
  description: Half-life (t1/2) of KO-2806 (in the absence and presence of food) and the combination agent
  measure: CL/F
  time frame: Cycle 1. Each cycle is 28 days. (Dose escalation and dose expansion).
  description: Oral clearance (CL/F) of KO-2806 and the combination agent
  measure: Vd/F
  time frame: Cycle 1. Each cycle is 28 days. (Dose escalation and dose expansion).
  description: Oral volume of distribution (Vd/F) of KO-2806 and the combination agent
  measure: QTcF
  time frame: Up to day 7 following first dose of KO-2806. Dose escalation.
  description: QT interval corrected for heart rate (HR) using Fridericia's formula (QTcF) for KO-2806 monotherapy (dose escalation)
  measure: KO-2806 plasma concentration measurements
  time frame: Up to day 7 following first dose of KO-2806. Dose escalation.
  measure: Amount of KO-2806 excretion in urine
  time frame: Up to 24 hours following first dose of KO-2806. Dose escalation.
  measure: CLr of KO-2806 excretion in urine
  time frame: Up to 24 hours following first dose of KO-2806. Dose escalation.
  description: Renal clearance of KO-2806 excretion in urine
  measure: t1/2 of KO-2806 excretion in urine
  time frame: Up to 24 hours following first dose of KO-2806. Dose escalation.
  description: Half-life of KO-2806 excretion in urine
  measure: Relative bioavailability of KO-2806 formulations
  time frame: Up to 24 hours following first dose of KO-2806. Dose expansion.
  arm group label: Arm #1: RAS-altered advanced solid tumors
  arm group type: Experimental
  description: Patients with advanced solid tumors and the following:
  HRAS-mutant and/or amplified tumors (any solid tumor type)
  HRAS overexpression (only for HNSCC tumors)
  KRAS and/or NRAS and/or HRAS-mutant and/or amplified for NSCLC or CRC
  KRAS-mutant and/or amplified PDAC
  arm group label: Arm #2: Advanced or metastatic ccRCC
  arm group type: Experimental
  description: Patients who have received at least 1 prior systemic therapy with IO-based treatment for locally advanced or metastatic RCC with predominantly clear cell subtype
  intervention type: Drug
  intervention name: KO-2806
  description: Oral administration
  arm group label: Arm #1: RAS-altered advanced solid tumors
  arm group label: Arm #2: Advanced or metastatic ccRCC
  intervention type: Drug
  intervention name: Cabozantinib
  description: Oral administration
  arm group label: Arm #2: Advanced or metastatic ccRCC
  other name: Cabometyx
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Clinical Operations
  phone: 617-588-3755
  email: KO-2806-001@kuraoncology.com
  responsible party type: Sponsor
  mesh term: Carcinoma, Renal Cell