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/NCT06039384</url>
    </required_header>
    <id_info>
      <org_study_id>INCB99280-204</org_study_id>
      <secondary_id>2023-503223-26-00</secondary_id>
      <nct_id>NCT06039384</nct_id>
    </id_info>
    <brief_title>A Study of INCB099280 in Combination With Adagrasib in Adults With Advanced Solid Tumors Harboring a KRASG12C Mutation</brief_title>
    <official_title>A Phase 1 Study of INCB099280 in Combination With Adagrasib in Adults With Advanced Solid Tumors Harboring a KRASG12C Mutation</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Incyte Corporation</agency>
        <agency_class>Industry</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>Mirati Therapeutics Inc.</agency>
        <agency_class>Industry</agency_class>
      </collaborator>
    </sponsors>
    <source>Incyte Corporation</source>
    <oversight_info>
      <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        The purpose of this study is to evaluate the safety and tolerability of INCB099280 in&#xD;
        combination with adagrasib and to establish the MTD or identify RDE(s) for the combination of&#xD;
        INCB099280 and adagrasib.&#xD;
      </textblock>
    </brief_summary>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">October 20, 2023</start_date>
    <completion_date type="Anticipated">November 3, 2025</completion_date>
    <primary_completion_date type="Anticipated">November 3, 2025</primary_completion_date>
    <phase>Phase 1</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>Part 1: Number of participants with Dose Limiting Toxicities (DLTs)</measure>
      <time_frame>Up to 28 days</time_frame>
      <description>Dose-limiting toxicity will be defined as the occurrence of any of the toxicities as per protocol.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Number of participants with Treatment-emergent Adverse Events (TEAEs)</measure>
      <time_frame>Up to 2 years and 90 days</time_frame>
      <description>Defined as adverse events reported for the first time or worsening of a pre-existing event after first dose of study drug.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Number of participants with TEAEs leading to dose modification or discontinuation</measure>
      <time_frame>Up to 2 years and 90 days</time_frame>
      <description>Number of participants with TEAEs leading to dose modification or discontinuation.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>INCB099280 and adagrasib plasma concentrations.</measure>
      <time_frame>Up to 2 years</time_frame>
      <description>PK parameters will be calculated from the blood plasma concentrations of INCB099280 and adagrasib using standard noncompartmental (model independent) PK methods.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Objective response rate (ORR)</measure>
      <time_frame>Up to 2 years</time_frame>
      <description>Defined as having a best overall response of complete response (CR) or partial response (PR) assessed per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 by the investigator.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Disease Control Rate (DCR)</measure>
      <time_frame>Up to 2 years</time_frame>
      <description>Defined as having a best overall response of CR, PR, or stable disease (SD) ≥ 15 weeks (from the start of treatment) assessed per RECIST v1.1 by the investigator.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Duration of Response (DOR)</measure>
      <time_frame>Up to 2 years</time_frame>
      <description>Defined as the time from the first CR or PR until disease progression (assessed per RECIST v1.1 by the investigator) or death from any cause, whichever occurs earlier.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Progression-free survival (PFS)</measure>
      <time_frame>Up to 12 months</time_frame>
      <description>Defined as absence of disease progression (assessed per RECIST v1.1 by the investigator) or death from any cause from start of treatment.</description>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">125</enrollment>
    <condition>Advanced Solid Tumors</condition>
    <arm_group>
      <arm_group_label>Part 1: Dose Finding</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>INCB099280 administered in combination with adagrasib in participants with previously treated KRAS glutamine to cysteine mutation at codon 12 (KRASG12C) mutant advanced solid tumors, will be evaluated to identify dose(s) for further evaluation in the dose expansion phase of the study.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Part 2: Dose Expansion</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Up to 80 participants will be enrolled in 1 of 2 disease-specific cohorts: Cohort A: previously treated KRASG12C mutated non-small cell lung cancer (NSCLC) Cohort B: previously treated KRASG12C-mutated colorectal cancer (CRC). Up to 3 doses may be selected from Part 1: Dose Finding for the Part 2: Dose Expansion.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>INCB099280</intervention_name>
      <description>Administered as specified in the treatment arm description</description>
      <arm_group_label>Part 1: Dose Finding</arm_group_label>
      <arm_group_label>Part 2: Dose Expansion</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>adagrasib</intervention_name>
      <description>Administered as specified in the treatment arm description</description>
      <arm_group_label>Part 1: Dose Finding</arm_group_label>
      <arm_group_label>Part 2: Dose Expansion</arm_group_label>
      <other_name>KRAZATI</other_name>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  KRASG12C-mutated solid malignancy determined by a sponsor-approved assay using either&#xD;
               tumor tissue or ctDNA.&#xD;
  &#xD;
            -  Histologically confirmed malignant solid tumor with locally advanced and/or metastatic&#xD;
               disease.&#xD;
  &#xD;
                 -  Only participants with NSCLC will be enrolled into Part 2 Cohort A.&#xD;
  &#xD;
                 -  Only participants with CRC will be enrolled into Part 2 Cohort B.&#xD;
  &#xD;
            -  Part 1: Disease progression on or after at least 1 prior systemic treatment.&#xD;
  &#xD;
            -  Part 2 (Cohort A - NSCLC): Received an anti-PD-(L)1-containing regimen and platinum&#xD;
               based chemotherapy regimen either concurrently or sequentially&#xD;
  &#xD;
            -  Part 2 (Cohort B - CRC): Received at least 1 line of systemic therapy that includes&#xD;
               the combination of fluoropyrimidine-based chemotherapy (in combination with&#xD;
               oxaliplatin and/or irinotecan) and either a vascular endothelial growth&#xD;
               factor-targeting monoclonal antibody or an anti-epidermal growth factor receptor&#xD;
               monoclonal antibody (if RAS wild type). Participants with MSI-H/dMMR CRC must also&#xD;
               have received a prior immune checkpoint inhibitor approved for this indication.&#xD;
  &#xD;
            -  Measurable disease according to RECIST v1.1.&#xD;
  &#xD;
            -  Eastern Cooperative Oncology Group performance status of 0 or 1.&#xD;
  &#xD;
            -  Estimated life expectancy &gt; 3 months.&#xD;
  &#xD;
            -  Willingness to avoid pregnancy.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Known additional malignancy that is progressing or requires active treatment.&#xD;
  &#xD;
            -  Central nervous system (CNS) metastases requiring treatment and/or leptomeningeal&#xD;
               disease.&#xD;
  &#xD;
            -  Part 2 only: Prior treatment with an approved or investigational agent targeting&#xD;
               KRASG12C.&#xD;
  &#xD;
            -  Toxicity from prior therapy that has not recovered to protocol-defined limits.&#xD;
  &#xD;
            -  Received thoracic radiation of &gt; 30 Gy within 6 months of the first dose of study&#xD;
               treatment.&#xD;
  &#xD;
            -  Participation in another interventional clinical study.&#xD;
  &#xD;
            -  History or evidence of interstitial lung disease, including noninfectious pneumonitis.&#xD;
  &#xD;
            -  Presence of gastrointestinal condition that may affect drug absorption.&#xD;
  &#xD;
            -  Active autoimmune disease requiring systemic treatment, including corticosteroids&#xD;
               exceeding a daily dose of 10 mg of prednisone or equivalent.&#xD;
  &#xD;
            -  Diagnosis of immunodeficiency or receiving chronic systemic steroid therapy exceeding&#xD;
               a daily dose of 10 mg of prednisone or equivalent.&#xD;
  &#xD;
            -  Active infection requiring systemic therapy.&#xD;
  &#xD;
            -  History of organ transplantation, including allogeneic stem cell transplantation.&#xD;
  &#xD;
            -  Receipt of systemic antibiotics within 28 days of the first dose of study treatment.&#xD;
  &#xD;
            -  Probiotic usage is prohibited during screening and throughout the study treatment&#xD;
               period.&#xD;
  &#xD;
            -  Received a live vaccine within 28 days of the planned start of study drug.&#xD;
  &#xD;
            -  Laboratory values outside the Protocol-defined ranges.&#xD;
  &#xD;
          Other protocol-defined Inclusion/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_official>
      <last_name>Incyte Medical Monitor</last_name>
      <role>Study Director</role>
      <affiliation>Incyte Corporation</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Incyte Corporation Call Center (US)</last_name>
      <phone>1.855.463.3463</phone>
      <email>medinfo@incyte.com</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Incyte Corporation Call Center (ex-US)</last_name>
      <phone>+800 00027423</phone>
      <email>eumedinfo@incyte.com</email>
    </overall_contact_backup>
    <verification_date>September 2023</verification_date>
    <study_first_submitted>September 8, 2023</study_first_submitted>
    <study_first_submitted_qc>September 8, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">September 15, 2023</study_first_posted>
    <last_update_submitted>September 8, 2023</last_update_submitted>
    <last_update_submitted_qc>September 8, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 15, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>KRASG12C mutation</keyword>
    <keyword>non-small cell lung cancer (NSCLC)</keyword>
    <keyword>colorectal cancer (CRC)</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Neoplasms</mesh_term>
    </condition_browse>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Adagrasib</mesh_term>
    </intervention_browse>
    <patient_data>
      <sharing_ipd>Yes</sharing_ipd>
      <ipd_description>Incyte shares data with qualified external researchers after a research proposal is submitted. These requests are reviewed and approved by a review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. The trial data availability is according to the criteria and process described on https://www.incyte.com/our-company/compliance-and-transparency</ipd_description>
      <ipd_info_type>Study Protocol</ipd_info_type>
      <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
      <ipd_time_frame>Data will be shared after the primary publication or 2 years after the study has ended for market authorized products and indications.</ipd_time_frame>
      <ipd_access_criteria>Data from eligible studies will be shared with qualified researchers according to the criteria and process described in the Data Sharing section of the www.incyteclinicaltrials.com website. For approved requests, the researchers will be granted access to anonymized data under the terms of a data sharing agreement.</ipd_access_criteria>
      <ipd_url>https://www.incyte.com/our-company/compliance-and-transparency</ipd_url>
    </patient_data>
    <!-- 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/NCT06039384
  org study id: INCB99280-204
  secondary id: 2023-503223-26-00
  nct id: NCT06039384
  lead sponsor: 
  collaborator: 
  is fda regulated drug: Yes
  is fda regulated device: No
  The purpose of this study is to evaluate the safety and tolerability of INCB099280 in
        combination with adagrasib and to establish the MTD or identify RDE(s) for the combination of
        INCB099280 and adagrasib.
  allocation: Randomized
  intervention model: Sequential Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Part 1: Number of participants with Dose Limiting Toxicities (DLTs)
  time frame: Up to 28 days
  description: Dose-limiting toxicity will be defined as the occurrence of any of the toxicities as per protocol.
  measure: Number of participants with Treatment-emergent Adverse Events (TEAEs)
  time frame: Up to 2 years and 90 days
  description: Defined as adverse events reported for the first time or worsening of a pre-existing event after first dose of study drug.
  measure: Number of participants with TEAEs leading to dose modification or discontinuation
  time frame: Up to 2 years and 90 days
  description: Number of participants with TEAEs leading to dose modification or discontinuation.
  measure: INCB099280 and adagrasib plasma concentrations.
  time frame: Up to 2 years
  description: PK parameters will be calculated from the blood plasma concentrations of INCB099280 and adagrasib using standard noncompartmental (model independent) PK methods.
  measure: Objective response rate (ORR)
  time frame: Up to 2 years
  description: Defined as having a best overall response of complete response (CR) or partial response (PR) assessed per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 by the investigator.
  measure: Disease Control Rate (DCR)
  time frame: Up to 2 years
  description: Defined as having a best overall response of CR, PR, or stable disease (SD) ≥ 15 weeks (from the start of treatment) assessed per RECIST v1.1 by the investigator.
  measure: Duration of Response (DOR)
  time frame: Up to 2 years
  description: Defined as the time from the first CR or PR until disease progression (assessed per RECIST v1.1 by the investigator) or death from any cause, whichever occurs earlier.
  measure: Progression-free survival (PFS)
  time frame: Up to 12 months
  description: Defined as absence of disease progression (assessed per RECIST v1.1 by the investigator) or death from any cause from start of treatment.
  arm group label: Part 1: Dose Finding
  arm group type: Experimental
  description: INCB099280 administered in combination with adagrasib in participants with previously treated KRAS glutamine to cysteine mutation at codon 12 (KRASG12C) mutant advanced solid tumors, will be evaluated to identify dose(s) for further evaluation in the dose expansion phase of the study.
  arm group label: Part 2: Dose Expansion
  arm group type: Experimental
  description: Up to 80 participants will be enrolled in 1 of 2 disease-specific cohorts: Cohort A: previously treated KRASG12C mutated non-small cell lung cancer (NSCLC) Cohort B: previously treated KRASG12C-mutated colorectal cancer (CRC). Up to 3 doses may be selected from Part 1: Dose Finding for the Part 2: Dose Expansion.
  intervention type: Drug
  intervention name: INCB099280
  description: Administered as specified in the treatment arm description
  arm group label: Part 1: Dose Finding
  arm group label: Part 2: Dose Expansion
  intervention type: Drug
  intervention name: adagrasib
  description: Administered as specified in the treatment arm description
  arm group label: Part 1: Dose Finding
  arm group label: Part 2: Dose Expansion
  other name: KRAZATI
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Incyte Medical Monitor
  role: Study Director
  affiliation: Incyte Corporation
  last name: Incyte Corporation Call Center (US)
  phone: 1.855.463.3463
  email: medinfo@incyte.com
  last name: Incyte Corporation Call Center (ex-US)
  phone: +800 00027423
  email: eumedinfo@incyte.com
  responsible party type: Sponsor
  mesh term: Neoplasms
  mesh term: Adagrasib
  sharing ipd: Yes
  ipd description: Incyte shares data with qualified external researchers after a research proposal is submitted. These requests are reviewed and approved by a review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. The trial data availability is according to the criteria and process described on https://www.incyte.com/our-company/compliance-and-transparency
  ipd info type: Study Protocol
  ipd info type: Statistical Analysis Plan (SAP)
  ipd time frame: Data will be shared after the primary publication or 2 years after the study has ended for market authorized products and indications.
  ipd access criteria: Data from eligible studies will be shared with qualified researchers according to the criteria and process described in the Data Sharing section of the www.incyteclinicaltrials.com website. For approved requests, the researchers will be granted access to anonymized data under the terms of a data sharing agreement.
  ipd url: https://www.incyte.com/our-company/compliance-and-transparency