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/NCT05975073</url>
    </required_header>
    <id_info>
      <org_study_id>20220127</org_study_id>
      <nct_id>NCT05975073</nct_id>
    </id_info>
    <brief_title>A Phase 1/2 Study of AMG 193 in Combination With IDE397 in Participants With Advanced Methylthioadenosine Phosphorylase (MTAP)-Null Solid Tumors</brief_title>
    <official_title>A Phase 1/2 Study Evaluating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of AMG 193 in Combination With IDE397 in Subjects With Advanced MTAP-null Solid Tumors</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Amgen</agency>
        <agency_class>Industry</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Amgen</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 main aims of this study are to evaluate the safety and tolerability, and to determine the&#xD;
        maximum tolerated dose (MTD) or the recommended combination dose of AMG 193 in combination&#xD;
        with IDE397 in adult participants with metastatic or locally advanced MTAP-null solid tumors,&#xD;
        and to evaluate the preliminary anti-tumor activity of AMG 193 in combination with IDE397 in&#xD;
        adult participants with metastatic or locally advanced MTAP-null Non-Small-Cell Lung Cancer&#xD;
        (NSCLC).&#xD;
      </textblock>
    </brief_summary>
    <overall_status>Recruiting</overall_status>
    <start_date type="Actual">August 1, 2023</start_date>
    <completion_date type="Anticipated">April 10, 2026</completion_date>
    <primary_completion_date type="Anticipated">October 10, 2025</primary_completion_date>
    <phase>Phase 1/Phase 2</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>Part 1: Number of Participants Experiencing Dose Limiting Toxicities (DLTs)</measure>
      <time_frame>Day 1 up to Day 21</time_frame>
    </primary_outcome>
    <primary_outcome>
      <measure>Part 1: Number of Participants Experiencing Treatment-emergent Adverse Events (TEAEs)</measure>
      <time_frame>Day 1 up to approximately 2.5 years</time_frame>
      <description>Any clinically significant changes in vital signs, electrocardiogram (ECG), or clinical laboratory test results will be recorded as adverse events</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Part 1: Number of Participants Experiencing Serious Adverse Events (SAEs)</measure>
      <time_frame>Day 1 up to approximately 2.5 years</time_frame>
    </primary_outcome>
    <primary_outcome>
      <measure>Part 2: Objective Response (OR) per modified Response Evaluation Criteria in Solid Tumors (RECIST) 1.1</measure>
      <time_frame>Day 1 up to approximately 2.5 years</time_frame>
    </primary_outcome>
    <secondary_outcome>
      <measure>Part 1 and 2: Maximal Plasma Concentration (Cmax) of AMG 193</measure>
      <time_frame>Day 1 pre-dose up to Cycle 5 (Cycle= 21 days)</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Part 1 and 2: Cmax of IDE397</measure>
      <time_frame>Day 1 pre-dose up to Cycle 5 (Cycle= 21 days)</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Part 1 and 2: Time to Achieve Maximal Plasma Concentration (Tmax) of AMG 193</measure>
      <time_frame>Day 1 pre-dose up to Cycle 5 (Cycle= 21 days)</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Part 1 and 2: Tmax of IDE397</measure>
      <time_frame>Day 1 pre-dose up to Cycle 5 (Cycle= 21 days)</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Parts 1 and 2: Area Under The Curve (AUC) After Single Dose of AMG 193</measure>
      <time_frame>Day 1 pre-dose up to Cycle 5 (Cycle= 21 days)</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Parts 1 and 2: Area Under The Curve (AUC) After Multiple Doses of AMG 193</measure>
      <time_frame>Day 1 pre-dose up to Cycle 5 (Cycle= 21 days)</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Parts 1 and 2: AUC After Single Dose of IDE397</measure>
      <time_frame>Day 1 pre-dose up to Cycle 5 (Cycle= 21 days)</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Parts 1 and 2: AUC After Multiple Doses of IDE397</measure>
      <time_frame>Day 1 pre-dose up to Cycle 5 (Cycle= 21 days)</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Parts 1: Overall Response per RECIST 1.1</measure>
      <time_frame>Day 1 up to end-of-study (EOS) (approximately 2.5 years)</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Parts 1 and 2: Disease Control Rate</measure>
      <time_frame>Day 1 up to EOS (approximately 2.5 years)</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Parts 1 and 2: Time to Response (TTR)</measure>
      <time_frame>Day 1 up to EOS (approximately 2.5 years)</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Parts 1 and 2: Duration of Response (DOR)</measure>
      <time_frame>Day 1 up to EOS (approximately 2.5 years)</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Parts 1 and 2: Duration of Stable Disease</measure>
      <time_frame>Day 1 up to EOT (approximately 6 months)</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Parts 1 and 2: Progression-free Survival (PFS)</measure>
      <time_frame>Day 1 up to EOS (approximately 2.5 years)</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Parts 1 and 2: Overall Survival (OS)</measure>
      <time_frame>Day 1 up to EOS (approximately 2.5 years)</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Part 2: Number of Participants Experiencing TEAEs</measure>
      <time_frame>Day 1 up to approximately 2.5 years</time_frame>
      <description>Any clinically significant changes in vital signs, electrocardiogram (ECG), or clinical laboratory test results will be recorded as adverse events</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Part 2: Number of Participants Experiencing SAEs</measure>
      <time_frame>Day 1 up to approximately 2.5 years</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Parts 1 and 2: Change From Baseline in Symmetric Dimethylation of Arginine (SDMA) in Blood</measure>
      <time_frame>Baseline (Day 1) to EOT plus 30 days (approximately 7 months)</time_frame>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">184</enrollment>
    <condition>MTAP-null Non-Small-Cell Lung Cancer</condition>
    <condition>MTAP-null Solid Tumors</condition>
    <arm_group>
      <arm_group_label>Part 1: Dose Exploration of AMG 193 Combined With IDE397</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Participants will receive escalating doses of AMG 193 and IDE397 administered orally (PO) in cycles of 21 days.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Part 2: Dose Expansion of AMG 193 Combined With IDE397</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>AMG 193 and IDE397 will be administered PO in cycles of 21 days.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>AMG 193</intervention_name>
      <description>Administered PO</description>
      <arm_group_label>Part 1: Dose Exploration of AMG 193 Combined With IDE397</arm_group_label>
      <arm_group_label>Part 2: Dose Expansion of AMG 193 Combined With IDE397</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>IDE397</intervention_name>
      <description>Administered PO</description>
      <arm_group_label>Part 1: Dose Exploration of AMG 193 Combined With IDE397</arm_group_label>
      <arm_group_label>Part 2: Dose Expansion of AMG 193 Combined With IDE397</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria&#xD;
  &#xD;
            1. Evidence of homozygous loss of MTAP (null) and/or MTAP deletion.&#xD;
  &#xD;
            2. Presence of advanced/metastatic solid tumor not amenable to curative treatment&#xD;
  &#xD;
                 1. Part 1: MTAP-null or lost MTAP expression solid tumor for which no standard&#xD;
                    therapy exists&#xD;
  &#xD;
                 2. Part 2: MTAP-null or lost MTAP expression NSCLC with progression after 1 to 2&#xD;
                    prior lines of systemic therapy.&#xD;
  &#xD;
            3. Able to swallow and retain PO administered study treatment and willing to record&#xD;
               adherence to investigational product&#xD;
  &#xD;
            4. Disease measurable as defined by RECIST v1.1&#xD;
  &#xD;
            5. Adequate organ function as defined in the protocol.&#xD;
  &#xD;
            6. Archived tumor tissue. Participants without archived tumor tissue available may be&#xD;
               allowed to enroll by undergoing tumor biopsy before cycle 1 day 1 dosing.&#xD;
  &#xD;
          Exclusion Criteria&#xD;
  &#xD;
            1. Prior treatment with an MAT2A inhibitor or a PRMT5 inhibitor.&#xD;
  &#xD;
            2. Radiologic or clinical evidence of spinal cord compression, untreated or symptomatic&#xD;
               brain metastases or leptomeningeal disease.&#xD;
  &#xD;
            3. Cardiovascular and pulmonary exclusion criteria as defined in the protocol.&#xD;
  &#xD;
            4. Gastrointestinal tract disease causing the inability to take PO medication,&#xD;
               malabsorption syndrome, requirement for IV alimentation, gastric/jejunal tube feeds,&#xD;
               uncontrolled inflammatory gastrointestinal disease (eg, Crohn's disease, ulcerative&#xD;
               colitis)&#xD;
  &#xD;
            5. History of bowel obstruction, abdominal fistula, gastrointestinal perforation, or&#xD;
               intra-abdominal abscess within 6 months of study entry.&#xD;
  &#xD;
            6. Prior irradiation to &gt; 25% of the bone marrow&#xD;
  &#xD;
            7. Use of prescription medications that are known strong CYP3A4/5 inducers or strong&#xD;
               CYP3A4/5 inhibitors within 7 days for CYP3A4/5 inhibitors, 14 days for CYP3A4/5&#xD;
               inducers or 5 half-lives, whichever is longer, prior to any dose of investigational&#xD;
               medical product.&#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>MD</last_name>
      <role>Study Director</role>
      <affiliation>Amgen</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Amgen Call Center</last_name>
      <phone>866-572-6436</phone>
      <email>medinfo@amgen.com</email>
    </overall_contact>
    <location>
      <facility>
        <name>City of Hope National Medical Center</name>
        <address>
          <city>Duarte</city>
          <state>California</state>
          <zip>91010</zip>
          <country>United States</country>
        </address>
      </facility>
      <status>Recruiting</status>
    </location>
    <location>
      <facility>
        <name>Next Oncology</name>
        <address>
          <city>Irving</city>
          <state>Texas</state>
          <zip>75039</zip>
          <country>United States</country>
        </address>
      </facility>
      <status>Recruiting</status>
    </location>
    <location_countries>
      <country>United States</country>
    </location_countries>
    <link>
      <url>http://www.amgentrials.com</url>
      <description>AmgenTrials clinical trials website</description>
    </link>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>July 19, 2023</study_first_submitted>
    <study_first_submitted_qc>July 27, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 3, 2023</study_first_posted>
    <last_update_submitted>August 24, 2023</last_update_submitted>
    <last_update_submitted_qc>August 24, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 28, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>Oncology</keyword>
    <keyword>AMG 193</keyword>
    <keyword>IDE397</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Carcinoma, Non-Small-Cell Lung</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>Yes</sharing_ipd>
      <ipd_description>De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.</ipd_description>
      <ipd_info_type>Study Protocol</ipd_info_type>
      <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
      <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
      <ipd_info_type>Clinical Study Report (CSR)</ipd_info_type>
      <ipd_time_frame>Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.</ipd_time_frame>
      <ipd_access_criteria>Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors. If not approved, a Data Sharing Independent Review Panel will arbitrate and make the final decision. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the URL below.</ipd_access_criteria>
      <ipd_url>https://www.amgen.com/datasharing</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/NCT05975073
  org study id: 20220127
  nct id: NCT05975073
  lead sponsor: 
  is fda regulated drug: Yes
  is fda regulated device: No
  The main aims of this study are to evaluate the safety and tolerability, and to determine the
        maximum tolerated dose (MTD) or the recommended combination dose of AMG 193 in combination
        with IDE397 in adult participants with metastatic or locally advanced MTAP-null solid tumors,
        and to evaluate the preliminary anti-tumor activity of AMG 193 in combination with IDE397 in
        adult participants with metastatic or locally advanced MTAP-null Non-Small-Cell Lung Cancer
        (NSCLC).
  allocation: Non-Randomized
  intervention model: Sequential Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Part 1: Number of Participants Experiencing Dose Limiting Toxicities (DLTs)
  time frame: Day 1 up to Day 21
  measure: Part 1: Number of Participants Experiencing Treatment-emergent Adverse Events (TEAEs)
  time frame: Day 1 up to approximately 2.5 years
  description: Any clinically significant changes in vital signs, electrocardiogram (ECG), or clinical laboratory test results will be recorded as adverse events
  measure: Part 1: Number of Participants Experiencing Serious Adverse Events (SAEs)
  time frame: Day 1 up to approximately 2.5 years
  measure: Part 2: Objective Response (OR) per modified Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
  time frame: Day 1 up to approximately 2.5 years
  measure: Part 1 and 2: Maximal Plasma Concentration (Cmax) of AMG 193
  time frame: Day 1 pre-dose up to Cycle 5 (Cycle= 21 days)
  measure: Part 1 and 2: Cmax of IDE397
  time frame: Day 1 pre-dose up to Cycle 5 (Cycle= 21 days)
  measure: Part 1 and 2: Time to Achieve Maximal Plasma Concentration (Tmax) of AMG 193
  time frame: Day 1 pre-dose up to Cycle 5 (Cycle= 21 days)
  measure: Part 1 and 2: Tmax of IDE397
  time frame: Day 1 pre-dose up to Cycle 5 (Cycle= 21 days)
  measure: Parts 1 and 2: Area Under The Curve (AUC) After Single Dose of AMG 193
  time frame: Day 1 pre-dose up to Cycle 5 (Cycle= 21 days)
  measure: Parts 1 and 2: Area Under The Curve (AUC) After Multiple Doses of AMG 193
  time frame: Day 1 pre-dose up to Cycle 5 (Cycle= 21 days)
  measure: Parts 1 and 2: AUC After Single Dose of IDE397
  time frame: Day 1 pre-dose up to Cycle 5 (Cycle= 21 days)
  measure: Parts 1 and 2: AUC After Multiple Doses of IDE397
  time frame: Day 1 pre-dose up to Cycle 5 (Cycle= 21 days)
  measure: Parts 1: Overall Response per RECIST 1.1
  time frame: Day 1 up to end-of-study (EOS) (approximately 2.5 years)
  measure: Parts 1 and 2: Disease Control Rate
  time frame: Day 1 up to EOS (approximately 2.5 years)
  measure: Parts 1 and 2: Time to Response (TTR)
  time frame: Day 1 up to EOS (approximately 2.5 years)
  measure: Parts 1 and 2: Duration of Response (DOR)
  time frame: Day 1 up to EOS (approximately 2.5 years)
  measure: Parts 1 and 2: Duration of Stable Disease
  time frame: Day 1 up to EOT (approximately 6 months)
  measure: Parts 1 and 2: Progression-free Survival (PFS)
  time frame: Day 1 up to EOS (approximately 2.5 years)
  measure: Parts 1 and 2: Overall Survival (OS)
  time frame: Day 1 up to EOS (approximately 2.5 years)
  measure: Part 2: Number of Participants Experiencing TEAEs
  time frame: Day 1 up to approximately 2.5 years
  description: Any clinically significant changes in vital signs, electrocardiogram (ECG), or clinical laboratory test results will be recorded as adverse events
  measure: Part 2: Number of Participants Experiencing SAEs
  time frame: Day 1 up to approximately 2.5 years
  measure: Parts 1 and 2: Change From Baseline in Symmetric Dimethylation of Arginine (SDMA) in Blood
  time frame: Baseline (Day 1) to EOT plus 30 days (approximately 7 months)
  arm group label: Part 1: Dose Exploration of AMG 193 Combined With IDE397
  arm group type: Experimental
  description: Participants will receive escalating doses of AMG 193 and IDE397 administered orally (PO) in cycles of 21 days.
  arm group label: Part 2: Dose Expansion of AMG 193 Combined With IDE397
  arm group type: Experimental
  description: AMG 193 and IDE397 will be administered PO in cycles of 21 days.
  intervention type: Drug
  intervention name: AMG 193
  description: Administered PO
  arm group label: Part 1: Dose Exploration of AMG 193 Combined With IDE397
  arm group label: Part 2: Dose Expansion of AMG 193 Combined With IDE397
  intervention type: Drug
  intervention name: IDE397
  description: Administered PO
  arm group label: Part 1: Dose Exploration of AMG 193 Combined With IDE397
  arm group label: Part 2: Dose Expansion of AMG 193 Combined With IDE397
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: MD
  role: Study Director
  affiliation: Amgen
  last name: Amgen Call Center
  phone: 866-572-6436
  email: medinfo@amgen.com
  facility: 
  status: Recruiting
  facility: 
  status: Recruiting
  country: United States
  url: http://www.amgentrials.com
  description: AmgenTrials clinical trials website
  responsible party type: Sponsor
  mesh term: Carcinoma, Non-Small-Cell Lung
  sharing ipd: Yes
  ipd description: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.
  ipd info type: Study Protocol
  ipd info type: Statistical Analysis Plan (SAP)
  ipd info type: Informed Consent Form (ICF)
  ipd info type: Clinical Study Report (CSR)
  ipd time frame: Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
  ipd access criteria: Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors. If not approved, a Data Sharing Independent Review Panel will arbitrate and make the final decision. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the URL below.
  ipd url: https://www.amgen.com/datasharing