[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"trial:NCT05967689":3,"trial-entities:NCT05967689":736,"trial-summary:NCT05967689":741},{"id":4,"nct_id":4,"org_study_id":5,"brief_title":6,"official_title":7,"overall_status":8,"completion_date":9,"status_verified_date":10,"last_update_date":11,"start_date":12,"sponsor_name":13,"lead_sponsor_class":14,"has_dmc":15,"brief_summary":16,"detailed_description":17,"conditions":18,"keywords":20,"study_type":30,"primary_purpose":31,"phases":32,"enrollment_info":34,"interventions":37,"primary_outcomes":62,"secondary_outcomes":68,"sex":128,"minimum_age":129,"maximum_age":130,"healthy_volunteers":15,"eligibility_criteria":131,"std_ages":159,"locations":162,"central_contacts":727,"overall_officials":733,"references":734,"see_also_links":735},"NCT05967689","TAS6417-201","A Study of Zipalertinib in Patients With Advanced Non-Small Cell Lung Cancer With Epidermal Growth Factor Receptor (EGFR) Exon 20 Insertions or Other Uncommon Mutation.","An Open-Label, Phase 2b, Global Multicenter Cohort Trial to Assess the Safety and Efficacy of Zipalertinib in Patients With Locally Advanced or Metastatic Non-Small Cell Lung Cancer With Exon 20 Insertion and Uncommon\u002FSingle or Compound Epidermal Growth Factor Receptor Mutations.","RECRUITING","2028-12-31","2026-08","2026-09-01","2023-07-31","Taiho Oncology, Inc.","INDUSTRY",false,"The purpose of this study is to evaluate the safety, efficacy and pharmacokinetics (PK) of zipalertinib in participants with locally advanced or metastatic Non-Small Cell Lung Cancer (NSCLC) harboring EGFR ex20ins mutations and other mutations.","This study will evaluate the safety and efficacy of zipalertinib in participants with locally advanced or metastatic NSCLC harboring EGFR ex20ins mutations or other uncommon\u002Fsingle or compound Epidermal Growth Factor Receptor Proteins Mutations (EGFRmts). The drug-drug interaction (DDI) substudy will assess the potential DDI effects of zipalertinib on the pharmacokinetics (PK) of cytochrome P450 (CYP) enzyme substrates and transporter substrates and also evaluate the relationship between zipalertinib concentration and QT interval change from baseline. Additionally, dose optimization substudy will be conducted to confirm an optimized dose of zipalertinib monotherapy.\n\nParticipants will be enrolled into 1 of the 4 following cohorts:\n\n* Cohort A (\"prior ex20ins treatment\") will include participants harboring EGFR ex20ins who have progressed on or after initial treatment with standard platinum-based chemotherapy and prior treatment with an ex20ins agent for their advanced disease (administered together or separately).\n* Cohort B (\"first-line\") will include participants harboring EGFR ex20ins who have not received prior treatment for advanced or metastatic disease and are not appropriate candidates for first-line doublet platinum-based chemotherapy or have refused first-line doublet platinum-based chemotherapy.\n* Cohort C (\"active brain mets\") will include participants harboring EGFR ex20ins or other uncommon single or compound EGFRmts and active brain metastases and\u002For leptomeningeal disease (LMD). Participants may or may not have had prior treatment for advanced disease.\n* Cohort D (\"other uncommon EGFRmts\") will include participants harboring other non-ex20ins, excluding C797S (uncommon single or compound) EGFRmts who have not received prior systemic therapy for their locally advanced or metastatic NSCLC disease.\n\nFor DDI substudy, participants will be enrolled in two groups:\n\n* CYP Cocktail Group will receive a single dose of cocktail of CYP enzyme probe substrates (CYP cocktail) alone prior to the start of zipalertinib dosing and a single dose of CYP cocktail in combination with zipalertinib at steady state.\n* Transporter Cocktail Group will receive a single dose of transporter probe substrates (Transporter cocktail) alone prior to the start of zipalertinib dosing and a single dose of Transporter cocktail in combination with zipalertinib at steady state.\n\nFor dose-optimization substudy, participants with locally advanced or metastatic NSCLC harboring epidermal growth factor receptor protein ex20ins mutations (EGFRmts) will be randomized to receive zipalertinib at different doses with continuous daily dosing until any discontinuation criterion is met. Participants will be enrolled into two groups: Arm A and Arm B, in which they will receive different doses of zipalertinib.",[19],"Advanced or Metastatic NSCLC Harboring Epidermal Growth Factor Receptor (EGFR) Exon 20 Insertion (ex20ins) Mutations",[21,22,23,24,25,26,27,28,29],"NSCLC","Carcinoma","Non-Small Cell Lung","Lung disease","locally advanced\u002F metastatic","ex20ins mutation","Insertion Mutations","EGFR uncommon\u002F single mutation Phase 2, Phase 2b, Phase II Exon 20","TAS6417\u002F CLN-081","INTERVENTIONAL","TREATMENT",[33],"PHASE2",{"count":35,"type":36},220,"ESTIMATED",[38,54,58],{"type":39,"name":40,"description":41,"armGroupLabels":42,"otherNames":51},"DRUG","TAS6417","Oral tablets",[43,44,45,46,47,48,49,50],"Cohort A (\"prior ex20ins treatment\")","Cohort B (\"first-line treatment\")","Cohort C (\"active brain mets\")","Cohort D (\"other uncommon EGFRmts\").","DDI Substudy: CYP Cocktail Group","DDI Substudy: Transporter Cocktail Group","Dose Optimization Substudy: Arm A","Dose Optimization Substudy: Arm B",[52,53],"CLN-081","zipalertinib",{"type":39,"name":55,"description":56,"armGroupLabels":57},"CYP Cocktail","Single dose of CYP enzyme probe substrates (CYP cocktail) alone prior to the start of zipalertinib dosing and a single dose of CYP cocktail in combination with zipalertinib at steady state.",[47],{"type":39,"name":59,"description":60,"armGroupLabels":61},"Transporter Cocktail","Single dose of transporter probe substrates (Transporter cocktail) alone prior to the start of zipalertinib dosing and a single dose of Transporter cocktail in combination with zipalertinib at steady state.",[48],[63,66],{"measure":64,"timeFrame":65},"Cohorts 1-4: Objective Response Rate (ORR)","Up to approximately 2 years",{"measure":67,"timeFrame":65},"Dose Optimization Substudy: ORR as Assessed by Blinded Independent Central Review (BICR)",[69,71,73,75,77,79,81,83,85,87,89,91,93,95,98,100,102,104,106,108,110,112,114,116,118,120,122,124,126],{"measure":70,"timeFrame":65},"Cohorts 1-4: Number of Participants With Treatment Emergent Adverse Events (TEAEs) Graded According to the National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (CTCAE v5.0)",{"measure":72,"timeFrame":65},"Cohorts 1-4: Number of Participants with Clinically Significant Changes in Clinical Laboratory Parameters",{"measure":74,"timeFrame":65},"Cohorts 1-4: Number of Participants with Clinically Significant Changes in Vital Signs",{"measure":76,"timeFrame":65},"Cohorts 1-4: Number of Participants with Clinically Significant Changes in Electrocardiogram (ECG) Parameters",{"measure":78,"timeFrame":65},"Cohorts 1-4: Number of participants With Change in Left Ventricular Ejection Fraction (LVEF) Evaluated Using Electrocardiography (ECHO) and Multigated Acquisition (MUGA) Scan",{"measure":80,"timeFrame":65},"Cohorts 1-4: Disease Control Rate (DCR)",{"measure":82,"timeFrame":65},"Cohorts 1-4: Duration of Response (DoR)",{"measure":84,"timeFrame":65},"Cohorts 1-4: Progression-free Survival (PFS)",{"measure":86,"timeFrame":65},"Cohorts 1-4: Overall Survival (OS)",{"measure":88,"timeFrame":65},"Cohort C: Intracranial (i) Overall Response Rate (iORR)",{"measure":90,"timeFrame":65},"Cohort C: Intracranial Duration of Complete Response (iDCR)",{"measure":92,"timeFrame":65},"Cohort C: Intracranial Duration of Response (iDoR)",{"measure":94,"timeFrame":65},"Cohorts 1-4: Minimum Plasma Concentration (Cmin) of Zipalertinib",{"measure":96,"timeFrame":97},"DDI Substudy: Change From Baseline in QT interval Corrected for Heart Rate using Fridericia's formula (QTcF) Interval Following Zipalertinib Administration in CYP Cocktail Group","Cycle 1 (cycle length = 21 days)",{"measure":99,"timeFrame":97},"DDI Substudy: Geometric Mean Maximum Plasma Concentration (Cmax) After Multiple Dose Administration of Zipalertinib in CYP Group and Transporter Cocktail Groups",{"measure":101,"timeFrame":97},"DDI Substudy: Geometric Mean Area Under Curve (AUC) After Multiple Dose Administration of Zipalertinib in CYP Group and Transporter Cocktail Groups",{"measure":103,"timeFrame":97},"DDI Substudy: Number of Participants with Treatment-Emergent Adverse Events (TEAEs) in CYP Group and Transporter Cocktail",{"measure":105,"timeFrame":65},"Dose Optimization Substudy: Duration of Response (DoR) as Assessed by BICR and Investigator",{"measure":107,"timeFrame":65},"Dose Optimization Substudy: Time to Response as Assessed by BICR and Investigator",{"measure":109,"timeFrame":65},"Dose Optimization Substudy: Percent Change in Tumor Size From Baseline as Assessed by BICR and Investigator",{"measure":111,"timeFrame":65},"Dose Optimization Substudy: DCR as Assessed by BICR and Investigator",{"measure":113,"timeFrame":65},"Dose Optimization Substudy: PFS as Assessed by BICR and Investigator",{"measure":115,"timeFrame":65},"Dose Optimization Substudy: 6 Month PFS Rate",{"measure":117,"timeFrame":65},"Dose Optimization Substudy: ORR as Assessed by Investigator",{"measure":119,"timeFrame":65},"Dose Optimization Substudy: Overall Survival (OS)",{"measure":121,"timeFrame":65},"Dose Optimization Substudy: Intracranial ORR (iORR) per Response Assessment in Neuro-oncology Brain Metastases (RANO-BM) Criteria",{"measure":123,"timeFrame":65},"Dose Optimization Substudy: Intracranial Duration of Response (iDOR)",{"measure":125,"timeFrame":65},"Dose Optimization Substudy: Intracranial Disease Control Rate (iDCR)",{"measure":127,"timeFrame":65},"Dose Optimization Substudy: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)","ALL","18 Years",null,{"inclusion":132,"exclusion":157,"raw_text":158},[133,134,135,136,137,138,139,140,141,142,143,144,145,146,147,148,149,150,151,152,153,154,155,156],"Documented EGFR ex20ins status, as determined by local testing performed at a Clinical Laboratory Improvement Amendments (CLIA) certified (United States \\[US\\]) or locally certified laboratory (outside the US).","Progressed on or after systemic therapy with an agent targeting ex20ins, either alone or in combination with standard platinum-based chemotherapy for the treatment of advanced disease. Participants who discontinued previous treatment due to unacceptable toxicity are eligible.","Participants with brain metastasis must be neurologically stable. Participants must have received central nervous system (CNS)-directed therapy and have no evidence of progression for at least 4 weeks after CNS-directed treatment, as ascertained by clinical examination and brain imaging (magnetic resonance imaging \\[MRI\\] or computed tomography \\[CT\\] scan) during the Screening Period. Additionally, they must be on a stable or decreasing dose of corticosteroids and\u002For anti-convulsant medications for at least 2 weeks prior to the first dose of study treatment. Participants with a history of uncontrolled seizures or LMD are not eligible.","Documented EGFR ex20instatus, as determined by local testing performed at a CLIA-certified (US) or locally certified laboratory (outside the US).","Participants who have not received prior treatment for advanced or metastatic disease and who are not appropriate candidates for first-line doublet platinum-based chemotherapy based on Investigator judgment or has refused first-line doublet platinum-based chemotherapy following discussion with the Investigator. Prior adjuvant\u002Fneoadjuvant treatment for early-stage disease must have been completed \\>6 months prior to the first dose of study treatment.","Participants with brain metastasis must be neurologically stable. Participants must have received CNS-directed therapy and have no evidence of progression for at least 4 weeks after CNS-directed treatment, as ascertained by clinical examination and brain imaging (MRI or CT scan) during the Screening Period, and they must be on a stable or decreasing dose of corticosteroids and\u002For anti-convulsant medications for at least 2 weeks prior to the first dose of study treatment. Participants with history of uncontrolled seizures or LMD are not eligible.","Documented ex20ins or other uncommon single or compound EGFR non-ex20ins status, as determined by local testing performed at a CLIA-certified (US) or locally certified laboratory (outside the US).","Presence of brain metastasis(es) characterized as at least one of the following:","Newly diagnosed and\u002For progressive brain metastasis(es) measurable by Response Assessment in Neuro-oncology Brain Metastases (RANO-BM) criteria and not subjected to CNS-directed therapy, AND\u002FOR","LMD measurable or non-measurable by RANO-BM criteria and confirmed by a positive cerebrospinal fluid cytology, or unequivocal radiographic and\u002For clinical determination.","Participants may not require other immediate CNS-directed therapy or will likely require other CNS directed anti-tumor therapy during the first cycle of study treatment, as judged by the Investigator.","Documented other uncommon single or compound EGFR non-ex20ins status (excluding C797S), as determined by local testing performed at a CLIA certified (US) or locally certified laboratory (outside the US). A list of eligible mutations will be provided in a separate document.","Participants with brain metastasis must be neurologically stable. Participants must have received CNS-directed therapy and have no evidence of progression for at least 4 weeks after CNS- directed treatment, as ascertained by clinical examination and brain imaging (MRI or CT scan) during the Screening Period, and they must be on a stable or decreasing dose of corticosteroids and\u002For anti-convulsant medications for at least 2 weeks prior to the first dose of study treatment. Participants with history of uncontrolled seizures or LMD are not eligible.","Participants who have not received prior systemic therapy for their locally advanced or metastatic NSCLC disease.","Prior adjuvant\u002Fneoadjuvant treatment for early-stage disease must have been completed \\>6 months prior to the first dose of study treatment. Participants may not have received prior adjuvant\u002Fneoadjuvant treatment with any EGFR tyrosine kinase inhibitor (TKI). 4. Measurable disease per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1). 5. Archival tumor tissue available for submission, with minimum quantity sufficient to evaluate EGFRmt status and, where possible, other biomarkers (details provided in a laboratory manual). Participants with insufficient tissue may be eligible following discussion with the Sponsor. 6. Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0 or 17. 7. Adequate organ function, as defined by the hematologic, renal and hepatic laboratory values. 8. Women of childbearing potential (WOCBP) must have a negative serum pregnancy test prior to administration of the first dose of study treatment. Female participants are not considered to be of childbearing potential if they are post-menopausal (no menses for 12 months without an alternative medical cause) or permanently sterile (hysterectomy, bilateral salpingectomy, or bilateral oophorectomy). 9. Both males and females of reproductive potential must agree to use effective birth control during the study prior to the first dose of study drug and for 1 month after the last dose of study treatment.","ex20ins EGFRmt OR","other uncommon, non-ex20ins EGFRmt (eg, G719X, L861Q, or S768I) OR","common EGFRmt (eg, ex19del or L858R) 2. Participant has progressed on or after receiving prior standard of care (SoC) systemic therapy for their locally advanced or metastatic NSCLC disease unless:","Participant for whom no approved therapy with demonstrated clinical benefit is indicated or available,","Participant is intolerant to the available first-line (1L) SoC treatment options, OR","Participant has refused 1L SoC treatment options (after being appropriately informed of the treatment options, risks, and benefits). 3. Participants with brain metastasis are eligible if they fulfill all of the criteria below:","Have received CNS-directed therapy and have no evidence of progression for at least 4 weeks after CNS- directed treatment, as ascertained by brain imaging (MRI or CT scan) during the Screening Period,","Are on a stable or decreasing dose of corticosteroids and\u002For anti-convulsant medications for at least 2 weeks prior to the first dose of study treatment,","Are neurologically stable with no history of uncontrolled seizures. 4. ECOG PS of 0 or 1.",[],"Inclusion Criteria:\n\n1. Written informed consent.\n2. ≥18 years of age (or meets the country's regulatory definition of legal adult age, whichever is greater.\n3. Pathologically confirmed, locally advanced or metastatic NSCLC meeting all the following criteria:\n\n   Cohort A participants:\n   * Documented EGFR ex20ins status, as determined by local testing performed at a Clinical Laboratory Improvement Amendments (CLIA) certified (United States \\[US\\]) or locally certified laboratory (outside the US).\n   * Progressed on or after systemic therapy with an agent targeting ex20ins, either alone or in combination with standard platinum-based chemotherapy for the treatment of advanced disease. Participants who discontinued previous treatment due to unacceptable toxicity are eligible.\n\n     i. Permitted prior ex20ins therapies include: amivantamab, sunvozertinib (DZD9008), and BLU451. Other prior ex20ins--directed treatment may be discussed with the Sponsor for eligibility assessment.\n   * Participants with brain metastasis must be neurologically stable. Participants must have received central nervous system (CNS)-directed therapy and have no evidence of progression for at least 4 weeks after CNS-directed treatment, as ascertained by clinical examination and brain imaging (magnetic resonance imaging \\[MRI\\] or computed tomography \\[CT\\] scan) during the Screening Period. Additionally, they must be on a stable or decreasing dose of corticosteroids and\u002For anti-convulsant medications for at least 2 weeks prior to the first dose of study treatment. Participants with a history of uncontrolled seizures or LMD are not eligible.\n\n   Cohort B participants:\n   * Documented EGFR ex20instatus, as determined by local testing performed at a CLIA-certified (US) or locally certified laboratory (outside the US).\n   * Participants who have not received prior treatment for advanced or metastatic disease and who are not appropriate candidates for first-line doublet platinum-based chemotherapy based on Investigator judgment or has refused first-line doublet platinum-based chemotherapy following discussion with the Investigator. Prior adjuvant\u002Fneoadjuvant treatment for early-stage disease must have been completed \\>6 months prior to the first dose of study treatment.\n   * Participants with brain metastasis must be neurologically stable. Participants must have received CNS-directed therapy and have no evidence of progression for at least 4 weeks after CNS-directed treatment, as ascertained by clinical examination and brain imaging (MRI or CT scan) during the Screening Period, and they must be on a stable or decreasing dose of corticosteroids and\u002For anti-convulsant medications for at least 2 weeks prior to the first dose of study treatment. Participants with history of uncontrolled seizures or LMD are not eligible.\n\n   Cohort C participants:\n   * Documented ex20ins or other uncommon single or compound EGFR non-ex20ins status, as determined by local testing performed at a CLIA-certified (US) or locally certified laboratory (outside the US).\n   * Presence of brain metastasis(es) characterized as at least one of the following:\n\n     * Newly diagnosed and\u002For progressive brain metastasis(es) measurable by Response Assessment in Neuro-oncology Brain Metastases (RANO-BM) criteria and not subjected to CNS-directed therapy, AND\u002FOR\n     * LMD measurable or non-measurable by RANO-BM criteria and confirmed by a positive cerebrospinal fluid cytology, or unequivocal radiographic and\u002For clinical determination.\n   * Participants may not require other immediate CNS-directed therapy or will likely require other CNS directed anti-tumor therapy during the first cycle of study treatment, as judged by the Investigator.\n\n   Cohort D participants:\n   * Documented other uncommon single or compound EGFR non-ex20ins status (excluding C797S), as determined by local testing performed at a CLIA certified (US) or locally certified laboratory (outside the US). A list of eligible mutations will be provided in a separate document.\n   * Participants with brain metastasis must be neurologically stable. Participants must have received CNS-directed therapy and have no evidence of progression for at least 4 weeks after CNS- directed treatment, as ascertained by clinical examination and brain imaging (MRI or CT scan) during the Screening Period, and they must be on a stable or decreasing dose of corticosteroids and\u002For anti-convulsant medications for at least 2 weeks prior to the first dose of study treatment. Participants with history of uncontrolled seizures or LMD are not eligible.\n   * Participants who have not received prior systemic therapy for their locally advanced or metastatic NSCLC disease.\n   * Prior adjuvant\u002Fneoadjuvant treatment for early-stage disease must have been completed \\>6 months prior to the first dose of study treatment. Participants may not have received prior adjuvant\u002Fneoadjuvant treatment with any EGFR tyrosine kinase inhibitor (TKI).\n4. Measurable disease per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1).\n5. Archival tumor tissue available for submission, with minimum quantity sufficient to evaluate EGFRmt status and, where possible, other biomarkers (details provided in a laboratory manual). Participants with insufficient tissue may be eligible following discussion with the Sponsor.\n6. Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0 or 17.\n7. Adequate organ function, as defined by the hematologic, renal and hepatic laboratory values.\n8. Women of childbearing potential (WOCBP) must have a negative serum pregnancy test prior to administration of the first dose of study treatment. Female participants are not considered to be of childbearing potential if they are post-menopausal (no menses for 12 months without an alternative medical cause) or permanently sterile (hysterectomy, bilateral salpingectomy, or bilateral oophorectomy).\n9. Both males and females of reproductive potential must agree to use effective birth control during the study prior to the first dose of study drug and for 1 month after the last dose of study treatment.\n\nDDI Substudy:\n\n1. Participant has pathologically confirmed, locally advanced or metastatic NSCLC:\n\n   a. Documented EGFRmt status as determined by local testing performed at a clinical laboratory improvement amendments (CLIA) certified (US) or locally certified laboratory (outside of the US) local laboratory, defined as either one of the following EGFRmts:\n   * ex20ins EGFRmt OR\n   * other uncommon, non-ex20ins EGFRmt (eg, G719X, L861Q, or S768I) OR\n   * common EGFRmt (eg, ex19del or L858R)\n2. Participant has progressed on or after receiving prior standard of care (SoC) systemic therapy for their locally advanced or metastatic NSCLC disease unless:\n\n   * Participant for whom no approved therapy with demonstrated clinical benefit is indicated or available,\n   * Participant is intolerant to the available first-line (1L) SoC treatment options, OR\n   * Participant has refused 1L SoC treatment options (after being appropriately informed of the treatment options, risks, and benefits).\n3. Participants with brain metastasis are eligible if they fulfill all of the criteria below:\n\n   * Have received CNS-directed therapy and have no evidence of progression for at least 4 weeks after CNS- directed treatment, as ascertained by brain imaging (MRI or CT scan) during the Screening Period,\n   * Are on a stable or decreasing dose of corticosteroids and\u002For anti-convulsant medications for at least 2 weeks prior to the first dose of study treatment,\n   * Are neurologically stable with no history of uncontrolled seizures.\n4. ECOG PS of 0 or 1.\n\nDose Optimization Substudy:\n\n1. Has pathologically confirmed, locally advanced or metastatic NSCLC meeting all the following criteria:\n\n   1. Documented EGFR ex20ins status, as determined by local testing performed at a CLIA certified (US) or locally certified laboratory (outside the US)\n   2. Progressed on or after systemic therapy standard platinum-based chemotherapy for the treatment of advanced disease. Participants who discontinued previous treatment due to unacceptable toxicity are eligible.\n\n   Note: Progression on or after systemic therapy with amivantamab is permitted (eg, given as monotherapy or in combination with chemotherapy).\n2. Participants with CNS metastases are eligible if both of the following criteria are met:\n\n   i. Measurable lesions according to RANO-BM defined as a contrast-enhancing lesion that can be accurately measured in at least one dimension, with a minimum size of 10 millimeters (mm), or at least 5 mm if MRI slice thickness is ≤ 1.5 mm ii. Previously received definitive local treatment and have stable CNS disease (defined as being neurologically stable and off corticosteroid for at least 2 weeks prior to enrollment) OR Asymptomatic CNS metastases ≤ 2 cm in size if, in the opinion of the investigator, immediate definitive treatment is not indicated.\n3. Measurable disease per RECIST 1.1.\n4. Has archival tumor tissue available for submission, with minimum quantity sufficient to evaluate EGFRmt status and, where possible, other biomarkers\n5. ECOG PS of 0 or 1.\n6. Has adequate organ function.\n\nExclusion Criteria:\n\n1. Participant is currently receiving an investigational drug in a clinical trial or participating in any other type of medical research judged to be scientifically or medically incompatible with this study.\n2. Has received any of the following within the specific time frame specified:\n\n   1. Participant has received Zipalertinib (TAS6417\u002FCLN081) at any time\n   2. CNS radiotherapy (gamma knife radiotherapy is allowed) ≤ 12 weeks, thoracic radiotherapy ≤ 28 days, or other palliative radiation ≤ 14 days prior to the first dose of study\n   3. Anticancer immunotherapy ≤28 days prior to the first dose of study treatment\n   4. Major surgery (excluding placement of vascular access) ≤28 days prior to the first dose of study treatment.\n   5. Any prior treatment with an EGFR exon20ins- targeted TKI\n   6. Participants with leptomeningeal CNS disease.\n3. Have any unresolved toxicity of Grade ≥2 from previous anticancer treatment, except for Grade 2 alopecia or skin pigmentation. Participants with other chronic but stable Grade 2 toxicities may be allowed to enroll after agreement between the Investigator and Sponsor.\n4. Past medical history of interstitial lung disease, treatment-related pneumonitis (any grade), or evidence of clinically active interstitial lung disease.\n5. Impaired cardiac function or clinically significant cardiac disease including any of the following:\n\n   1. History of congestive heart failure (CHF) Class III\u002FIV according to the New York Heart Association (NYHA) Functional Classification.\n   2. Serious cardiac arrhythmias requiring treatment.\n   3. Resting corrected QT interval (QTc) \\>470 msec using Fridericia's formula (QTcF).\n6. Is unable to swallow tablets or has any disease or condition that may significantly affect gastrointestinal absorption of zipalertinib (eg, inflammatory bowel disease, malabsorption syndrome, or prior gastric\u002Fbowel resection).\n7. History of another primary malignancy ≤2 years prior to the date of first dose of study treatment unless at least one of the following criteria are met:\n\n   1. Adequately treated basal or squamous cell carcinoma of the skin\n   2. Cancer in situ of the breast or cervix\n   3. Participants with previously treated malignancy if all treatment for that malignancy was completed at least 2 years prior to first dose and no evidence of disease\n   4. Participants with concurrent malignancy clinically stable and not requiring tumor-directed treatment\n8. Known history of hepatitis B, hepatitis C, or human immunodeficiency virus (HIV) that is not controlled with treatment.\n9. History of Coronavirus disease 2019 (COVID-19) infection within 4 weeks prior to enrollment and\u002For has persistent clinically significant pulmonary symptoms related to prior COVID-19 infection.\n10. Active bleeding disorders.\n11. Known hypersensitivity to the ingredients in zipalertinib or any drugs similar in structure or class.\n12. Is pregnant, lactating, or planning to become pregnant.\n13. The participant is, in the Investigator's opinion, unable or unwilling to comply with the trial procedures.",[160,161],"ADULT","OLDER_ADULT",[163,173,181,189,197,205,212,219,227,234,241,248,256,263,270,278,286,294,302,311,315,323,331,340,348,356,364,372,380,387,395,402,411,418,425,432,440,448,456,463,470,477,484,493,498,506,514,521,529,534,539,543,550,559,566,570,578,586,591,599,603,607,614,623,630,634,638,645,652,656,660,664,673,680,687,693,697,706,713,720],{"facility":164,"status":165,"city":166,"state":167,"zip":168,"country":169,"geoPoint":170},"University of Alabama at Birmingham","WITHDRAWN","Birmingham","Alabama","35294","United States",{"lat":171,"lon":172},33.52066,-86.80249,{"facility":174,"status":8,"city":175,"state":176,"zip":177,"country":169,"geoPoint":178},"City of Hope - Duarte","Duarte","California","91010",{"lat":179,"lon":180},34.13945,-117.97729,{"facility":182,"status":8,"city":183,"state":184,"zip":185,"country":169,"geoPoint":186},"Beth Israel Deaconess Medical Center","Boston","Massachusetts","02215",{"lat":187,"lon":188},42.35843,-71.05977,{"facility":190,"status":8,"city":191,"state":192,"zip":193,"country":169,"geoPoint":194},"Comprehensive Cancer Centers of Nevada - Central Valley - Twain","Las Vegas","Nevada","89169",{"lat":195,"lon":196},36.17497,-115.13722,{"facility":198,"status":8,"city":199,"state":200,"zip":201,"country":169,"geoPoint":202},"Memorial Sloan Kettering Cancer Center - Basking Ridge","Basking Ridge","New Jersey","07920",{"lat":203,"lon":204},40.70621,-74.54932,{"facility":206,"status":8,"city":207,"state":200,"zip":208,"country":169,"geoPoint":209},"Memorial Sloan Kettering Cancer Center - Monmouth","Middletown","07748",{"lat":210,"lon":211},40.39428,-74.11709,{"facility":213,"status":8,"city":214,"state":200,"zip":215,"country":169,"geoPoint":216},"Memorial Sloan Kettering Cancer Center - Bergen","Montvale","07645",{"lat":217,"lon":218},41.04676,-74.02292,{"facility":220,"status":8,"city":221,"state":222,"zip":223,"country":169,"geoPoint":224},"Memorial Sloan Kettering Cancer Center - Commack","Commack","New York","11725",{"lat":225,"lon":226},40.84288,-73.29289,{"facility":228,"status":8,"city":229,"state":222,"zip":230,"country":169,"geoPoint":231},"Memorial Sloan Kettering Cancer Center - 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It includes different groups (cohorts) based on prior treatment.","completed","A Study of Zipalertinib for Advanced Non-Small Cell Lung Cancer with EGFR Exon 20 Insertions","This study is testing a drug called zipalertinib in people with advanced non-small cell lung cancer (NSCLC) that has specific changes in the EGFR gene, called exon 20 insertions or other uncommon mutations. Researchers want to see how safe and effective zipalertinib is. You might be able to join if you are 18 or older, have this type of lung cancer, and have either received prior treatment or are newly diagnosed and cannot have standard chemotherapy. The main goal is to see how many people respond to zipalertinib, meaning their cancer shrinks or stops growing. This will be measured for up to about two years. The study also looks at how zipalertinib interacts with other medications in your body. The current recruitment status is unclear, and the study plans to enroll 220 participants.","The main outcomes will be measured for up to approximately two years.",133,"Not specified in the trial record.","Not stated in the trial record.",[]]