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/NCT05973773</url>
    </required_header>
    <id_info>
      <org_study_id>TAS6417-301</org_study_id>
      <secondary_id>2023-503575-21</secondary_id>
      <nct_id>NCT05973773</nct_id>
    </id_info>
    <brief_title>A Study of Zipalertinib and Chemotherapy Compared With Chemotherapy Alone in Patients With Advanced Non-Small Cell Lung Cancer With Epidermal Growth Factor Receptor (EGFR) Exon 20 Insertion.</brief_title>
    <acronym>REZILIENT3</acronym>
    <official_title>Randomized, Controlled, Open-label, Phase 3, Global Multi - Center Trial to Assess the Efficacy and Safety of Zipalertinib Plus Chemotherapy Versus Chemotherapy Alone, in Patients With Previously Untreated, Locally Advanced or Metastatic Nonsquamous Non-Small Cell Lung Cancer (NSCLC) With Epidermal Growth Factor Receptor (EGFR) Exon 20 Insertion (ex20ins) Mutations</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Taiho Oncology, Inc.</agency>
        <agency_class>Industry</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Taiho Oncology, Inc.</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>
      <is_us_export>Yes</is_us_export>
    </oversight_info>
    <brief_summary>
      <textblock>
        The purpose of this study is to will evaluate the safety and efficacy of zipalertinib in&#xD;
        combination with standard first-line platinum-based chemotherapy compared to chemotherapy&#xD;
        alone, in patients with locally advanced or metastatic NSCLC with EGFR ex20ins mutations.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        This study will evaluate the efficacy and safety of zipalertinib in combination with standard&#xD;
        chemotherapy with pemetrexed and a platinum agent (either carboplatin or cisplatin) in&#xD;
        patients with previously untreated, locally advanced or metastatic nonsquamous NSCLC&#xD;
        harboring EGFR ex20ins mutations.&#xD;
  &#xD;
        The study will be conducted in two parts:&#xD;
  &#xD;
          -  Part A: Safety lead-in to determine the recommended dose of zipalertinib in combination&#xD;
             with standard chemotherapy pemetrexed and a platinum agent (either carboplatin or&#xD;
             cisplatin) to be studied in Part B of the study.&#xD;
  &#xD;
          -  Part B: Randomized, controlled, open-label, multinational Phase 3 study to assess the&#xD;
             efficacy and safety of zipalertinib in combination with standard chemotherapy with&#xD;
             pemetrexed and a platinum agent (either carboplatin or cisplatin) compared to standard&#xD;
             chemotherapy alone. An independent data monitoring committee (IDMC) will be established&#xD;
             to monitor interim safety Data.&#xD;
  &#xD;
        A treatment cycle is defined as 21 days for both parts of the study.&#xD;
  &#xD;
        Part A: Safety Lead-In The primary objective of Part A is to determine the recommended dose&#xD;
        of zipalertinib administered in combination with pemetrexed and a platinum agent (either&#xD;
        carboplatin or cisplatin) to be studied in the Phase 3 portion of this study.&#xD;
  &#xD;
        Approximately 6-12 patients will receive zipalertinib administered at an initial dose of&#xD;
        zipalertinib PO BID (Dose Level 1) in combination with pemetrexed and carboplatin or&#xD;
        cisplatin on a 21-day cycle. Patients may continue to receive study treatment until&#xD;
        documentation of progressive disease (PD) or until other withdrawal criteria are met,&#xD;
        whichever comes first. Patients will be enrolled using a rolling-6 design,35 and the&#xD;
        determination of the dose of zipalertinib to be used in Part B of the study will be informed&#xD;
        by the incidence of dose-limiting toxicities (DLTs) observed during Cycle 1.&#xD;
  &#xD;
        Part B: Phase 3 Enrollment into the Phase 3 portion of the study will begin following&#xD;
        completion of Part A.&#xD;
  &#xD;
        Approximately 300 patients will be randomized on a 1:1 basis to receive pemetrexed and a&#xD;
        platinum agent (either carboplatin or cisplatin) with or without zipalertinib on a 21-day&#xD;
        cycle.&#xD;
  &#xD;
        Carboplatin or cisplatin will be administered for 4 cycles. Patients may continue to receive&#xD;
        zipalertinib (experimental study arm) and pemetrexed (both study arms) until documentation of&#xD;
        PD or until other withdrawal criteria are met, whichever comes first.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Recruiting</overall_status>
    <start_date type="Actual">June 30, 2023</start_date>
    <completion_date type="Anticipated">May 21, 2026</completion_date>
    <primary_completion_date type="Anticipated">January 30, 2026</primary_completion_date>
    <phase>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>Part A and B: The rate and severity of treatment emergent AEs</measure>
      <time_frame>approximately 5 years</time_frame>
    </primary_outcome>
    <primary_outcome>
      <measure>Part A and Part B: Progression-free survival (PFS) by blinded independent central review (BICR)</measure>
      <time_frame>approximately 5 years</time_frame>
    </primary_outcome>
    <primary_outcome>
      <measure>Part A: The rate and severity of DLTs according to the NCI-Common Terminology Criteria of Adverse Events (CTCAE) v5.0 during Cycle 1</measure>
      <time_frame>approximately 5 years</time_frame>
    </primary_outcome>
    <secondary_outcome>
      <measure>Part A and Part B: Objective response rate (ORR)</measure>
      <time_frame>approximately 5 years</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Part A and Part B: Disease control rate (DCR)</measure>
      <time_frame>approximately 5 years</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Part A and Part B: Duration of response (DoR)</measure>
      <time_frame>approximately 5 years</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Part A and Part B: Intracranial (i) Overall Response Rate (iORR)</measure>
      <time_frame>approximately 5 years</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Part A and Part B: Intracranial duration of complete response (iDCR)</measure>
      <time_frame>approximately 5 years</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Part A and Part B: Intracranial duration of Response (iDoR)</measure>
      <time_frame>approximately 5 years</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Part B: Overall survival (OS)</measure>
      <time_frame>approximately 5 years</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Pharmacokinetic (PK) parameter</measure>
      <time_frame>approximately 5 years</time_frame>
      <description>Minimum observed concentration (Cmin)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>European Quality of Life 5 Dimensions, 3 Level Version (EQ-5D-3L)</measure>
      <time_frame>approximately 5 years</time_frame>
      <description>The EQ-5D-3L descriptive system comprises the following five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 3 levels: no problems, some problems, and extreme problems. The patient is asked to indicate his/her health state by ticking the box next to the most appropriate statement in each of the five dimensions. This decision results into a 1-digit number that expresses the level selected for that dimension. The digits for the five dimensions can be combined into a 5-digit number that describes the patient's health state. This scale is numbered from 0 to 100. The higher the score the better the outcome</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30</measure>
      <time_frame>approximately 5 years</time_frame>
      <description>The EORTC QLQ-C30 is a &quot;core questionnaire&quot; which incorporates a range of physical, emotional and social health developed to assess the quality of life of cancer patients. This scale is numbered from 30 to 130. The higher the score equates to better functioning.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Non-small Lung Cancer Symptom Assessment Questionnaire (NSCLC-SAQ )</measure>
      <time_frame>approximately 5 years</time_frame>
      <description>The NSCLC- SAQ was developed to incorporate the patient's perspective into evaluation of clinical benefit in advanced non-small cell lung cancer trials.. Qualitative evidence supports 7 items covering 5 symptom concepts with the total score measuring overall severity of the following NSCLC symptoms: cough, pain, dyspnea, fatigue, and appetite. Lower scores indicate lower symptom severity.</description>
    </secondary_outcome>
    <other_outcome>
      <measure>Pharmacokinetic (PK) parameter</measure>
      <time_frame>approximately 5 years</time_frame>
      <description>Minimum Plasma Concentration [Cmin]</description>
    </other_outcome>
    <other_outcome>
      <measure>Pharmacokinetic (PK) parameter</measure>
      <time_frame>approximately 5 years</time_frame>
      <description>Maximum Plasma Concentration [Cmax]</description>
    </other_outcome>
    <other_outcome>
      <measure>Pharmacokinetic (PK) parameter</measure>
      <time_frame>approximately 5 years</time_frame>
      <description>Area Under Curve [AUC]</description>
    </other_outcome>
    <other_outcome>
      <measure>EGFR mutation status</measure>
      <time_frame>approximately 5 years</time_frame>
      <description>local central tests results</description>
    </other_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">312</enrollment>
    <condition>Advanced or Metastatic NSCLS With Exon 20 Insertion Mutation</condition>
    <arm_group>
      <arm_group_label>Part A (Safety Lead in)</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Part A: Safety Lead-In Approximately 6-12 patients will receive zipalertinib administered at an initial dose of zipalertinib PO BID (Dose Level 1) in combination with pemetrexed and carboplatin or cisplatin on a 21-day cycle. Patients may continue to receive study treatment until documentation of progressive disease (PD) or until other withdrawal criteria are met, whichever comes first.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Part B</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Part B: Phase 3 Enrollment into the Phase 3 portion of the study will begin following completion of Part A.&#xD;
  Approximately 300 patients will be randomized on a 1:1 basis to receive pemetrexed and a platinum agent (either carboplatin or cisplatin) with or without zipalertinib on a 21-day cycle.&#xD;
  Carboplatin or cisplatin will be administered for 4 cycles. Patients may continue to receive zipalertinib (experimental study arm) and pemetrexed (both study arms) until documentation of PD or until other withdrawal criteria are met, whichever comes first.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>TAS6417</intervention_name>
      <description>oral tablets/capsules</description>
      <arm_group_label>Part A (Safety Lead in)</arm_group_label>
      <arm_group_label>Part B</arm_group_label>
      <other_name>Zipalertinib</other_name>
      <other_name>CLN-081</other_name>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. Provide written informed consent.&#xD;
  &#xD;
            2. ≥18 years of age (or meets the country's regulatory definition for legal adult age,&#xD;
               whichever is greater).&#xD;
  &#xD;
            3. Pathologically confirmed, locally advanced or metastatic nonsquamous NSCLC&#xD;
  &#xD;
            4. Has not received any prior systemic treatment for their locally advanced or metastatic&#xD;
               nonsquamous NSCLC. Prior adjuvant/neoadjuvant treatment for advanced or metastatic&#xD;
               disease &gt;6 months prior to first dose of study treatment is allowed for early-stage&#xD;
               NSCLC.&#xD;
  &#xD;
            5. Documented EGFR mutation status, as determined by local testing performed at a CLIA&#xD;
               certified or equivalent laboratory, defined as follows:&#xD;
  &#xD;
                 1. Part A: ex20ins or other common single or compound EGFR mutation&#xD;
  &#xD;
                 2. Part B: ex20ins EGFR mutation&#xD;
  &#xD;
            6. Archival tumor tissue available for submission, with minimum quantity sufficient to&#xD;
               evaluate EGFR mutation status and, where possible, other biomarkers. Patients with&#xD;
               insufficient tissue (details provided in laboratory manual) may be eligible following&#xD;
               discussion with the sponsor; a fresh biopsy will not be required.&#xD;
  &#xD;
            7. Patients with previously treated brain metastasis(es) and stable CNS disease (defined&#xD;
               as being neurologically stable and receiving a stable or decreasing corticosteroid&#xD;
               dose at time of enrollment) are eligible.&#xD;
  &#xD;
            8. At least one measurable lesion as determined per RECIST 1.1 for patients enrolling to&#xD;
               Part B. Patients enrolling to Part A may be enrolled without measurable disease.&#xD;
  &#xD;
            9. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.10. Adequate organ&#xD;
               function, as defined by the laboratory value&#xD;
  &#xD;
           10. Have a life expectancy of at least 3 months as assessed by the investigator.&#xD;
  &#xD;
           11. Women of childbearing potential (WOCBP) must have a negative serum pregnancy test&#xD;
               prior to administration of the first dose of study treatment. Female patients are not&#xD;
               considered to be of childbearing potential if they are postmenopausal (no menses for&#xD;
               12 months without an alternative medical cause) or permanently sterile (hysterectomy,&#xD;
               bilateral salpingectomy, or bilateral oophorectomy).&#xD;
  &#xD;
           12. Both males and females of reproductive potential must agree to use effective birth&#xD;
               control during the study prior to the first dose and for 6 months after the last dose&#xD;
               of study treatment or longer, based on local requirements.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. Is currently receiving an investigational drug in a clinical trial or participating in&#xD;
               any other type of medical research judged not to be scientifically or medically&#xD;
               compatible with this study.&#xD;
  &#xD;
            2. Prior treatment with any of the following within the specific time frame specified:&#xD;
  &#xD;
                 1. Zipalertinib (TAS6417/CLN-081) at any time.&#xD;
  &#xD;
                 2. Thoracic radiotherapy ≤28 days, palliative radiation of nonthoracic disease ≤14&#xD;
                    days, or palliative radiation of a single lesion ≤7 days prior to first dose of&#xD;
                    study treatment.&#xD;
  &#xD;
                 3. Major surgery (excluding placement of vascular access) ≤28 days prior to first&#xD;
                    dose of study treatment.&#xD;
  &#xD;
            3. Have any unresolved toxicity of Grade ≥2 from previous anticancer treatment in the&#xD;
               neoadjuvant or adjuvant setting, except for Grade 2 alopecia or skin pigmentation.&#xD;
  &#xD;
            4. Patients with other chronic but stable Grade 2 toxicities may be allowed to enroll&#xD;
               after agreement between the investigator and Sponsor.&#xD;
  &#xD;
            5. Past medical history of interstitial lung disease, treatment-related pneumonitis (any&#xD;
               grade), or any evidence of clinically active interstitial lung disease.&#xD;
  &#xD;
            6. Impaired cardiac function or clinically significant cardiac disease, including any of&#xD;
               the following:&#xD;
  &#xD;
                 1. History of congestive heart failure (CHF) Class III/IV according to the New York&#xD;
                    Heart Association (NYHA) Functional Classification (Appendix A).&#xD;
  &#xD;
                 2. Serious cardiac arrhythmias requiring treatment.&#xD;
  &#xD;
                 3. Resting corrected QT interval (QTc) &gt;470 msec calculated using Fridericia's&#xD;
                    formula (QTcF).&#xD;
  &#xD;
            7. Unable to swallow tablets/capsules or has any disease or condition that may&#xD;
               significantly affect gastrointestinal (GI) absorption of zipalertinib (such as&#xD;
               inflammatory bowel disease, malabsorption syndrome, or prior GI resection). History of&#xD;
               another primary malignancy ≤2 years prior to the date of first dose of study treatment&#xD;
               unless at least one of the following criteria are met:&#xD;
  &#xD;
                 1. Adequately treated basal or squamous cell carcinoma of the skin&#xD;
  &#xD;
                 2. Cancer of the breast or cervix in situ&#xD;
  &#xD;
                 3. Previously treated malignancy, if all treatment for that malignancy was completed&#xD;
                    at least 2 years prior to first dose of study treatment, and no current evidence&#xD;
                    of disease&#xD;
  &#xD;
                 4. Concurrent malignancy determined to be clinically stable and not requiring tumor&#xD;
                    directed treatment&#xD;
  &#xD;
            8. Known history of hepatitis B, hepatitis C, or human immunodeficiency virus (HIV) that&#xD;
               is unstable or not controlled with treatment.&#xD;
  &#xD;
            9. History of COVID-19 infection within 4 weeks prior to enrolment and/or have&#xD;
               persistent, clinically significant pulmonary symptoms related to prior COVID-19&#xD;
               infection.&#xD;
  &#xD;
           10. Active bleeding disorders.&#xD;
  &#xD;
           11. Known hypersensitivity to the ingredients in zipalertinib or any drugs similar in&#xD;
               structure or class.&#xD;
  &#xD;
           12. Is unable or unwilling to take dexamethasone, folic acid, and/or vitamin B12&#xD;
               supplementation during treatment with pemetrexed.&#xD;
  &#xD;
           13. Is pregnant or lactating.&#xD;
  &#xD;
           14. The patient is, in the investigator's opinion, unable or unwilling to comply with the&#xD;
               trial procedures.&#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>Taiho Oncology, INC</last_name>
      <phone>609-250-7336</phone>
      <email>clinicaltrialinfo@taihooncology.com</email>
    </overall_contact>
    <location>
      <facility>
        <name>Gabrail Cancer and Research Center</name>
        <address>
          <city>Canton</city>
          <state>Ohio</state>
          <zip>44718</zip>
          <country>United States</country>
        </address>
      </facility>
      <status>Recruiting</status>
    </location>
    <location_countries>
      <country>United States</country>
    </location_countries>
    <verification_date>July 2023</verification_date>
    <study_first_submitted>July 11, 2023</study_first_submitted>
    <study_first_submitted_qc>July 25, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 3, 2023</study_first_posted>
    <last_update_submitted>August 23, 2023</last_update_submitted>
    <last_update_submitted_qc>August 23, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 25, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>Exon 20 insertion mutation</keyword>
    <keyword>NSCLC</keyword>
    <keyword>phase 3</keyword>
    <keyword>Lung disease</keyword>
    <keyword>Carcinoma, Non-Small-Cell Lung</keyword>
    <keyword>CLN-081</keyword>
    <keyword>TAS6417</keyword>
    <keyword>EGFR</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>
    <!-- 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/NCT05973773
  org study id: TAS6417-301
  secondary id: 2023-503575-21
  nct id: NCT05973773
  lead sponsor: 
  has dmc: Yes
  is fda regulated drug: Yes
  is fda regulated device: No
  is us export: Yes
  The purpose of this study is to will evaluate the safety and efficacy of zipalertinib in
        combination with standard first-line platinum-based chemotherapy compared to chemotherapy
        alone, in patients with locally advanced or metastatic NSCLC with EGFR ex20ins mutations.
  This study will evaluate the efficacy and safety of zipalertinib in combination with standard
        chemotherapy with pemetrexed and a platinum agent (either carboplatin or cisplatin) in
        patients with previously untreated, locally advanced or metastatic nonsquamous NSCLC
        harboring EGFR ex20ins mutations.
  
        The study will be conducted in two parts:
  
          -  Part A: Safety lead-in to determine the recommended dose of zipalertinib in combination
             with standard chemotherapy pemetrexed and a platinum agent (either carboplatin or
             cisplatin) to be studied in Part B of the study.
  
          -  Part B: Randomized, controlled, open-label, multinational Phase 3 study to assess the
             efficacy and safety of zipalertinib in combination with standard chemotherapy with
             pemetrexed and a platinum agent (either carboplatin or cisplatin) compared to standard
             chemotherapy alone. An independent data monitoring committee (IDMC) will be established
             to monitor interim safety Data.
  
        A treatment cycle is defined as 21 days for both parts of the study.
  
        Part A: Safety Lead-In The primary objective of Part A is to determine the recommended dose
        of zipalertinib administered in combination with pemetrexed and a platinum agent (either
        carboplatin or cisplatin) to be studied in the Phase 3 portion of this study.
  
        Approximately 6-12 patients will receive zipalertinib administered at an initial dose of
        zipalertinib PO BID (Dose Level 1) in combination with pemetrexed and carboplatin or
        cisplatin on a 21-day cycle. Patients may continue to receive study treatment until
        documentation of progressive disease (PD) or until other withdrawal criteria are met,
        whichever comes first. Patients will be enrolled using a rolling-6 design,35 and the
        determination of the dose of zipalertinib to be used in Part B of the study will be informed
        by the incidence of dose-limiting toxicities (DLTs) observed during Cycle 1.
  
        Part B: Phase 3 Enrollment into the Phase 3 portion of the study will begin following
        completion of Part A.
  
        Approximately 300 patients will be randomized on a 1:1 basis to receive pemetrexed and a
        platinum agent (either carboplatin or cisplatin) with or without zipalertinib on a 21-day
        cycle.
  
        Carboplatin or cisplatin will be administered for 4 cycles. Patients may continue to receive
        zipalertinib (experimental study arm) and pemetrexed (both study arms) until documentation of
        PD or until other withdrawal criteria are met, whichever comes first.
  allocation: Randomized
  intervention model: Sequential Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Part A and B: The rate and severity of treatment emergent AEs
  time frame: approximately 5 years
  measure: Part A and Part B: Progression-free survival (PFS) by blinded independent central review (BICR)
  time frame: approximately 5 years
  measure: Part A: The rate and severity of DLTs according to the NCI-Common Terminology Criteria of Adverse Events (CTCAE) v5.0 during Cycle 1
  time frame: approximately 5 years
  measure: Part A and Part B: Objective response rate (ORR)
  time frame: approximately 5 years
  measure: Part A and Part B: Disease control rate (DCR)
  time frame: approximately 5 years
  measure: Part A and Part B: Duration of response (DoR)
  time frame: approximately 5 years
  measure: Part A and Part B: Intracranial (i) Overall Response Rate (iORR)
  time frame: approximately 5 years
  measure: Part A and Part B: Intracranial duration of complete response (iDCR)
  time frame: approximately 5 years
  measure: Part A and Part B: Intracranial duration of Response (iDoR)
  time frame: approximately 5 years
  measure: Part B: Overall survival (OS)
  time frame: approximately 5 years
  measure: Pharmacokinetic (PK) parameter
  time frame: approximately 5 years
  description: Minimum observed concentration (Cmin)
  measure: European Quality of Life 5 Dimensions, 3 Level Version (EQ-5D-3L)
  time frame: approximately 5 years
  description: The EQ-5D-3L descriptive system comprises the following five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 3 levels: no problems, some problems, and extreme problems. The patient is asked to indicate his/her health state by ticking the box next to the most appropriate statement in each of the five dimensions. This decision results into a 1-digit number that expresses the level selected for that dimension. The digits for the five dimensions can be combined into a 5-digit number that describes the patient's health state. This scale is numbered from 0 to 100. The higher the score the better the outcome
  measure: European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30
  time frame: approximately 5 years
  description: The EORTC QLQ-C30 is a "core questionnaire" which incorporates a range of physical, emotional and social health developed to assess the quality of life of cancer patients. This scale is numbered from 30 to 130. The higher the score equates to better functioning.
  measure: Non-small Lung Cancer Symptom Assessment Questionnaire (NSCLC-SAQ )
  time frame: approximately 5 years
  description: The NSCLC- SAQ was developed to incorporate the patient's perspective into evaluation of clinical benefit in advanced non-small cell lung cancer trials.. Qualitative evidence supports 7 items covering 5 symptom concepts with the total score measuring overall severity of the following NSCLC symptoms: cough, pain, dyspnea, fatigue, and appetite. Lower scores indicate lower symptom severity.
  measure: Pharmacokinetic (PK) parameter
  time frame: approximately 5 years
  description: Minimum Plasma Concentration [Cmin]
  measure: Pharmacokinetic (PK) parameter
  time frame: approximately 5 years
  description: Maximum Plasma Concentration [Cmax]
  measure: Pharmacokinetic (PK) parameter
  time frame: approximately 5 years
  description: Area Under Curve [AUC]
  measure: EGFR mutation status
  time frame: approximately 5 years
  description: local central tests results
  arm group label: Part A (Safety Lead in)
  arm group type: Experimental
  description: Part A: Safety Lead-In Approximately 6-12 patients will receive zipalertinib administered at an initial dose of zipalertinib PO BID (Dose Level 1) in combination with pemetrexed and carboplatin or cisplatin on a 21-day cycle. Patients may continue to receive study treatment until documentation of progressive disease (PD) or until other withdrawal criteria are met, whichever comes first.
  arm group label: Part B
  arm group type: Experimental
  description: Part B: Phase 3 Enrollment into the Phase 3 portion of the study will begin following completion of Part A.
  Approximately 300 patients will be randomized on a 1:1 basis to receive pemetrexed and a platinum agent (either carboplatin or cisplatin) with or without zipalertinib on a 21-day cycle.
  Carboplatin or cisplatin will be administered for 4 cycles. Patients may continue to receive zipalertinib (experimental study arm) and pemetrexed (both study arms) until documentation of PD or until other withdrawal criteria are met, whichever comes first.
  intervention type: Drug
  intervention name: TAS6417
  description: oral tablets/capsules
  arm group label: Part A (Safety Lead in)
  arm group label: Part B
  other name: Zipalertinib
  other name: CLN-081
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Taiho Oncology, INC
  phone: 609-250-7336
  email: clinicaltrialinfo@taihooncology.com
  facility: 
  status: Recruiting
  country: United States
  responsible party type: Sponsor
  mesh term: Carcinoma, Non-Small-Cell Lung