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. (REZILIENT2)

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/Single or Compound Epidermal Growth Factor Receptor Mutations.

The purpose of this study is to evaluate the safety and efficacy of zipalertinib in patients with locally advanced or metastatic NSCLC harboring EGFR ex20ins mutations and other mutations.

Study Overview

• Status: Recruiting
• Conditions: Advanced or Metastatic NSCLC Harboring Epidermal Growth Factor Receptor (EGFR) Exon 20 Insertion (ex20ins) Mutations
• Intervention / Treatment: Drug: TAS6417

Detailed Description

This study will evaluate the safety and efficacy of zipalertinib in patients with locally advanced or metastatic NSCLC harboring EGFR ex20ins mutations or other uncommon/single or compound EGFRmt.

Patients will be enrolled into 1 of the 4 following cohorts:

• Cohort A ("prior ex20ins treatment") will include patients harboring EGFR ex20ins mutations who have progressed on or after initial treatment with standard platinum-based chemotherapy and prior treatment with an ex20 agent for their advanced disease (administered together or separately).
• Cohort B ("1st line") will include patients harboring EGFR ex20ins mutations who have not received prior treatment for advanced disease.
• Cohort C ("active brain mets") will include patients harboring EGFR ex20ins or other uncommon single and compound mutations and active brain metastases. Patients may or may not have had prior treatment for advanced disease.
• Cohort D ("other uncommon EGFRmt") will include patients harboring other, non ex20ins uncommon single or compound EGFRmt who have progressed on or after treatment with standard systemic anticancer therapy.

• Study Type: Interventional
• Enrollment (Estimated): 160
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Taiho Oncology, INC; Phone Number: 609-250-7336; Email: clinicaltrialinfo@taihooncology.com

Study Locations

• Australia
  • Melbourne, Australia
    • Not yet recruiting
    • Joondalup Health campus
    • Principal Investigator: Arman Hasani
  • Saint Leonards, Australia, 2065
    • Recruiting
    • GenesisCare - North Shore
  • New South Wales
    • Bankstown, New South Wales, Australia, 2200
      • Not yet recruiting
      • Bankstown-Lidcombe Hospital
    • Saint Leonards, New South Wales, Australia, 2065
      • Recruiting
      • GenesisCare - North Shore
  • Western Australia
    • Joondalup, Western Australia, Australia, 6027
      • Not yet recruiting
      • Joondalup Health campus
• Canada
  • Brampton, Canada, L6R 3J7
    • Not yet recruiting
    • William Osler Health System - Brampton Civic Hospital
  • Quebec
    • Montréal, Quebec, Canada, H4A 3J1
      • Not yet recruiting
      • McGill University Health Centre
• France
  • Aslace
    • Strasbourg cedex, Aslace, France, 67091
      • Not yet recruiting
      • Les Hôpitaux Universitaires de Strasbourg
  • Basse-Normandie
    • Caen cedex 9, Basse-Normandie, France, 14033
      • Not yet recruiting
      • Hôpital Côte de Nacre
  • Ile-de-France
    • Paris cedex 05, Ile-de-France, France, 75248
      • Not yet recruiting
      • Institut Curie
  • Limousin
    • Limoges cedex, Limousin, France, 87042
      • Not yet recruiting
      • Centre Hospitalier Universitaire Limoges
  • Loire-Atlantique
    • Saint-Herblain, Loire-Atlantique, France, 44805
      • Recruiting
      • Centre Hospitalier Universitaire De Nantes - Hôpital Nord Laennec
  • Nouvelle-Aquitaine
    • Pessac, Nouvelle-Aquitaine, France, 33604
      • Not yet recruiting
      • Hôpital Haut-Lévèque
  • Provence Alpes Cote d'Azure
    • Avignon cedex 9, Provence Alpes Cote d'Azure, France, 84918
      • Not yet recruiting
      • Institut Sainte Catherine
  • Provence Alpes Cote d´Azur
    • Marseille, Provence Alpes Cote d´Azur, France, 13015
      • Not yet recruiting
      • Hopital Nord de Marseille
  • Rhone-Alpes
    • Lyon, Rhone-Alpes, France, 69008
      • Not yet recruiting
      • Centre LEON BERARD
  • Val-de-Marne
    • Villejuif, Val-de-Marne, France, 94805
      • Not yet recruiting
      • Gustave Roussy
  • Île-de-France
    • Boulogne-Billancourt, Île-de-France, France, 92100
      • Not yet recruiting
      • Hôpital Ambroise-Paré
• Germany
  • München, Germany, 80337
    • Not yet recruiting
    • LMU Klinikum - Campus Innenstadt
  • Regensburg, Germany, 93053
    • Not yet recruiting
    • Universitätsklinikum Regensburg
  • Baden-Wuerttemberg
    • Esslingen, Baden-Wuerttemberg, Germany, 73730
      • Not yet recruiting
      • Klinikum Esslingen
  • Hamburg (Hansestadt)
    • Hamburg, Hamburg (Hansestadt), Germany, 22763
      • Not yet recruiting
      • Asklepios Klinik Altona
  • Hassen
    • Kassel, Hassen, Germany, 34125
      • Not yet recruiting
      • Klinikum Kassel
  • Hessen
    • Gießen, Hessen, Germany, 35392
      • Not yet recruiting
      • Universitätsklinikum Gießen und Marburg - Gießen
  • Niedersachsen
    • Oldenburg, Niedersachsen, Germany, 26121
      • Not yet recruiting
      • Pius-Hospital Oldenburg
  • Nordrhein-Westfalen
    • Köln, Nordrhein-Westfalen, Germany, 50937
      • Not yet recruiting
      • Universität zu Köln
  • SAchsen
    • Dresden, SAchsen, Germany, 01301
      • Not yet recruiting
      • Universitatsklinikum Carl Gustav Carus Dresden
• Hong Kong
  • Hong Kong Island
    • Pok Fu Lam, Hong Kong Island, Hong Kong
      • Not yet recruiting
      • Queen Mary Hospital - Hong Kong
  • New Territories
    • Sha Tin, New Territories, Hong Kong
      • Not yet recruiting
      • The Chinese University of Hong Kong
• Italy
  • Alessandria, Italy, 15121
    • Not yet recruiting
    • Azienda Ospedaliera Nazionale SS. Antonio e Biagio e Cesare Arrigo - Alessandria
  • Bologna, Italy, 40138
    • Not yet recruiting
    • Azienda Ospedaliero-Universitaria di Bologna - Policlinico Sant Orsola-Malpighi
  • Catania, Italy, 95125
    • Not yet recruiting
    • Azienda Ospedaliero Universitaria Policlinico Gaspare Rodolico - San Marco
  • Cremona, Italy, 26100
    • Not yet recruiting
    • Ospedale di Cremona
  • Genova, Italy, 16132
    • Not yet recruiting
    • Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) - Ospedale Policlinico San Martino
  • Milan, Italy, 20132
    • Not yet recruiting
    • Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) - Ospedale San Raffaele
  • Modena, Italy, 41124
    • Not yet recruiting
    • Azienda Ospedaliero - Universitaria di Modena
  • Napoli, Italy, 80138
    • Not yet recruiting
    • Azienda Ospedaliera Universitaria - Università degli Studi della Campania Luigi Vanvitelli
  • Parma, Italy, 43126
    • Not yet recruiting
    • Azienda Ospedaliero-Universitaria di Parma
  • Pavia, Italy, 27100
    • Not yet recruiting
    • Fondazione IRCCS Policlinico San Matteo
  • Piacenza, Italy, 29121
    • Not yet recruiting
    • Azienda Unità Sanitaria Locale - Piacenza
  • Ravenna, Italy, 48121
    • Not yet recruiting
    • Azienda Unità Sanitaria Locale della Romagna
  • Roma, Italy, 00144
    • Not yet recruiting
    • Istituto Nazionale Tumori Regina Elena
  • Emilia-romagna
    • Ravenna, Emilia-romagna, Italy, 48121
      • Not yet recruiting
      • Istituto Romagnolo per lo Studio dei Tumori "Dino Amadori" - IRST
  • Florence
    • Firenze, Florence, Italy, 50134
      • Not yet recruiting
      • Azienda Ospedaliero - Universitaria Careggi
• Japan
  • Niigata, Japan, 951-8566
    • Recruiting
    • Niigata Cancer Center Hospital
  • Okayama, Japan, 700-8558
    • Recruiting
    • Okayama University Hospital
  • Tokyo, Japan, 104-0045
    • Recruiting
    • National Cancer Center Hospital
  • Aiti
    • Nagoya, Aiti, Japan, 464-8681
      • Recruiting
      • Aichi Cancer Center
  • Hukuoka
    • Fukuoka-shi, Hukuoka, Japan, 811-1395
      • Recruiting
      • Kyushu Cancer Center
  • Miyagi
    • Sendai, Miyagi, Japan, 980-0873
      • Recruiting
      • Sendai Kousei Hospital
  • Osaka
    • Ōsaka-sayama-Shi, Osaka, Japan, 589-8511
      • Recruiting
      • Kindai University Hospital
  • Sizuoka
    • Sunto-gun, Sizuoka, Japan, 411-8777
      • Recruiting
      • Shizuoka Cancer Center
  • Tiba
    • Kashiwa-shi, Tiba, Japan, 277-8577
      • Recruiting
      • National Cancer Center Hospital East
  • Tokyo
    • Koto, Tokyo, Japan, 135-8550
      • Recruiting
      • Cancer Institute Hospital of JFCR
• Korea, Republic of
  • Gyeonggi-Do
    • Seongnam-si, Gyeonggi-Do, Korea, Republic of, 13620
      • Not yet recruiting
      • Seoul National University Bundang Hospital
  • Gyeonggi-do
    • Goyang-si, Gyeonggi-do, Korea, Republic of, 10408
      • Not yet recruiting
      • National Cancer Center - Korea
    • Suwon-si, Gyeonggi-do, Korea, Republic of, 16499
      • Not yet recruiting
      • Ajou University Hospital
    • Suwon-si, Gyeonggi-do, Korea, Republic of, 16247
      • Not yet recruiting
      • Catholic University of Korea Saint Vincent's Hospital
  • Gyeongsangnamdo [Kyongsangnam-do]
    • Jinju, Gyeongsangnamdo [Kyongsangnam-do], Korea, Republic of, 52727
      • Not yet recruiting
      • Gyeongsang National University Hospital
  • Incheon Gwang'yeogsi [Inch'on-Kwangyokshi]
    • Incheon, Incheon Gwang'yeogsi [Inch'on-Kwangyokshi], Korea, Republic of, 22332
      • Not yet recruiting
      • Inha University Hospital
  • Jeollanam-do
    • Hwasun, Jeollanam-do, Korea, Republic of, 58128
      • Not yet recruiting
      • Chonnam National University Hwasun Hospital
  • Seoul Teugbyeolsi [Seoul-T'ukpyolshi]
    • Seoul, Seoul Teugbyeolsi [Seoul-T'ukpyolshi], Korea, Republic of, 08308
      • Not yet recruiting
      • Korea University Guro Hospital
    • Seoul, Seoul Teugbyeolsi [Seoul-T'ukpyolshi], Korea, Republic of, 03080
      • Not yet recruiting
      • Seoul National University Hospital
    • Seoul, Seoul Teugbyeolsi [Seoul-T'ukpyolshi], Korea, Republic of, 05505
      • Not yet recruiting
      • Asan Medical Center
    • Soeul, Seoul Teugbyeolsi [Seoul-T'ukpyolshi], Korea, Republic of, 06591
      • Not yet recruiting
      • The Catholic University of Korea - Seoul St. Mary's Hospital
• Spain
  • Barcelona, Spain, 08036
    • Not yet recruiting
    • Hospital Clínic de Barcelona
  • Barcelona, Spain, 08023
    • Recruiting
    • Hospital Quironsalud Barcelona
  • Barcelona, Spain
    • Not yet recruiting
    • Hospital de la Santa Creu i Sant Pau
  • Barcelona, Spain, 08017
    • Not yet recruiting
    • Clinica Mi Tres Torres
  • Jaén, Spain, 23007
    • Not yet recruiting
    • Hospital Universitario de Jaén
  • Madrid, Spain, 28046
    • Recruiting
    • Hospital Universitario La Paz
  • Madrid, Spain, 28040
    • Not yet recruiting
    • Hospital Universitario Fundacion Jimenez Diaz
  • Madrid, Spain, 28041
    • Not yet recruiting
    • Hospital Universitario 12 de octubre
  • Madrid, Spain, 28033
    • Not yet recruiting
    • MD Anderson Cancer Center Madrid
  • Barcelona
    • L'Hospitalet De Llobregat, Barcelona, Spain, 08908
      • Not yet recruiting
      • Institut Català d'Oncologia - Hospital Duran i Reynals (ICO L'Hospitalet)
  • La Coruña
    • A Coruña, La Coruña, Spain, 15006
      • Not yet recruiting
      • Complejo Hospitalario Universitario A Coruña
  • Malaga
    • Málaga, Malaga, Spain, 29010
      • Not yet recruiting
      • Hospital Regional Universitario de Málaga - Hospital General
• Turkey
  • Adana, Turkey, 01040
    • Not yet recruiting
    • Medical Park Seyhan Hastanesi
  • Adana, Turkey, 01370
    • Not yet recruiting
    • T.C. Saglik Bakanligi Adana Sehir Egitim ve Arastirma Hastanesi
  • Ankara, Turkey, 06100
    • Not yet recruiting
    • Hacettepe Universitesi Kanser Enstitusu
  • Ankara, Turkey, 6520
    • Not yet recruiting
    • Memorial Ankara Hastanesi
  • Edirne, Turkey, 22030
    • Not yet recruiting
    • Trakya Universitesi Saglik Arastirma ve Uygulama Merkezi
  • Istanbul, Turkey, 34214
    • Not yet recruiting
    • Bagcilar Medipol Mega Universite Hastanesi
  • Istanbul, Turkey, 34722
    • Not yet recruiting
    • T.C. Saglik Bakanligi - Istanbul Il Saglik Mudurlugu - Goztepe Prof. Dr. Suleyman Yalcin Sehir Hastanesi
  • Ankara
    • Cankaya, Ankara, Turkey, 06800
      • Not yet recruiting
      • T.C. Saglik Bakanligi Ankara Bilkent Sehi?r Hastanesi?
    • Etlik, Ankara, Turkey, 06010
      • Not yet recruiting
      • Ankara Il Saglik Mudurlugu SBU Gulhane Egitim Ve Arastirma Hastanesi
  • Diyarbakir
    • Sur, Diyarbakir, Turkey, 21280
      • Not yet recruiting
      • Dicle Universitesi Tip Fakultesi
  • Istanbul
    • Esenyurt, Istanbul, Turkey, 34517
      • Not yet recruiting
      • Istinye Üniversite Hastanesi Liv Hospital Bahcesehir
• United Kingdom
  • England
    • London, England, United Kingdom, NW3 2QG
      • Not yet recruiting
      • Royal Free London NHS Foundation Trust
    • Manchester, England, United Kingdom, M20 4BX
      • Not yet recruiting
      • The Christie NHS Foundation Trust
    • Nottingham, England, United Kingdom, NG5 1PB
      • Recruiting
      • Nottingham University Hospitals NHS Trust
    • Torquay, England, United Kingdom, TQ2 7AA
      • Not yet recruiting
      • Torbay and South Devon NHS Foundation Trust
    • Wirral, England, United Kingdom, CH63 4JY
      • Not yet recruiting
      • The Clatterbridge Cancer Centre NHS Foundation Trust
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • Not yet recruiting
      • O'Neal Comprehensive Cancer Center at the University of Alabama at Birmingham
  • California
    • Duarte, California, United States, 91010
      • Recruiting
      • City of Hope - Duarte (Main Campus)
    • Huntington Beach, California, United States, 92648
      • Recruiting
      • City of Hope - Huntington Beach
    • Irvine, California, United States, 92618
      • Recruiting
      • City of Hope Orange County Lennar Foundation Cancer Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Not yet recruiting
      • Beth Israel Deaconess Medical Center
  • Nevada
    • Henderson, Nevada, United States, 89052
      • Recruiting
      • Comprehensive Cancer Centers of Nevada - Henderson
    • Henderson, Nevada, United States, 89052
      • Recruiting
      • Comprehensive Cancer Centers of Nevada - Horizon Ridge Henderson
    • Henderson, Nevada, United States, 89074
      • Recruiting
      • Comprehensive Cancer Centers of Nevada - Southeast Henderson - Stephanie
    • Las Vegas, Nevada, United States, 89128
      • Recruiting
      • Comprehensive Cancer Centers of Nevada - Northwest
    • Las Vegas, Nevada, United States, 89144
      • Recruiting
      • Comprehensive Cancer Centers of Nevada - Summerlin Medical Center II
    • Las Vegas, Nevada, United States, 89148
      • Recruiting
      • Comprehensive Cancer Centers of Nevada - Southwest
    • Las Vegas, Nevada, United States, 89169
      • Recruiting
      • Comprehensive Cancer Centers of Nevada - Central Valley - Twain
  • New York
    • New York, New York, United States, 10065
      • Not yet recruiting
      • Memorial Sloan Kettering Cancer Center - New York
  • Ohio
    • Canton, Ohio, United States, 44718
      • Recruiting
      • Gabrail Cancer and Research Center
    • Columbus, Ohio, United States, 43219
      • Not yet recruiting
      • SCRI - Mark H. Zangmeister Cancer Center
    • Toledo, Ohio, United States, 43623
      • Not yet recruiting
      • The Toledo Clinic Cancer Center
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Not yet recruiting
      • Tennessee Oncology - Nashville - Centennial Clinic - Medical Oncology
  • Virginia
    • Arlington, Virginia, United States, 22205
      • Recruiting
      • Virginia Cancer Specialists - Arlington Office
    • Fairfax, Virginia, United States, 22031
      • Recruiting
      • Virginia Cancer Specialists - Fairfax Office
    • Gainesville, Virginia, United States, 20155
      • Recruiting
      • Virginia Cancer Specialists - Gainesville Office
    • Reston, Virginia, United States, 20190
      • Recruiting
      • Virginia Cancer Specialists - Reston
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Not yet recruiting
      • Froedtert and Medical College of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Written informed consent
2. ≥18 years of age (or meets the country's regulatory definition of legal adult age, whichever is greater

3. Pathologically confirmed, locally advanced or metastatic NSCLC meeting all the following criteria:

   Cohort A patients:

   • Documented EGFR ex20ins mutation status, as determined by local testing performed at a CLIA certified (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. Patients who discontinued previous treatment due to unacceptable toxicity are eligible.
   • Patients with brain metastasis must be neurologically stable. Patients 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/or anti-convulsant medications for at least 2 weeks prior to the first dose of study treatment. Patients with history of uncontrolled seizures or leptomeningeal disease are not eligible.

   Cohort B patients:

   • Documented EGFR ex20ins mutation status, as determined by local testing performed at a CLIA certified (US) or locally certified laboratory (outside the US).
   • Not received prior systemic therapy for locally advanced or metastatic disease. Prior adjuvant/neoadjuvant treatment for early-stage disease must have been completed >6 months prior to the first dose of study treatment.
   • Patients with brain metastasis must be neurologically stable. Patients 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/or anti-convulsant medications for at least 2 weeks prior to the first dose of study treatment. Patients with history of uncontrolled seizures or leptomeningeal disease are not eligible.

   Cohort C patients:

   • Documented EGFR ex20ins mutation status, as determined by local testing performed at a CLIA certified (US) or locally certified laboratory (outside the US).

   • Presence of brain metastasis(es), which may be measurable or nonmeasurable by RANO-BM criteria, characterized as one of the following:

     • Newly diagnosed and/or progressive brain metastasis (es) not subjected to CNS-directed therapy, OR
     • Leptomeningeal disease (LMD) confirmed by a positive cerebrospinal fluid cytology, or unequivocal radiographic and/or clinical determination.

   Cohort D patients:

   • Documented other non-ex20ins uncommon single or compound EGFRmt status, 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 manual.
   • Patients with brain metastasis must be neurologically stable. Patients 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/or anti-convulsant medications for at least 2 weeks prior to the first dose of study treatment. Patients with history of uncontrolled seizures or leptomeningeal disease are not eligible.
4. Measurable disease per 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). Patients with insufficient tissue may be eligible following discussion with the sponsor.
6. Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0 or 17. Adequate organ function, as defined by the hematologic, renal and hepatic laboratory values

4. Women of childbearing potential (WOCBP) must have a negative serum pregnancy test prior to administration of the first dose of study treatment. Female patients 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).

5. 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 6 months after the last dose of study treatment.

Exclusion Criteria:

1. Patient 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.

2. Has received any of the following within the specific time frame specified:

   1. Patient has received Zipalertinib (TAS6417/CLN081) at any time
   2. Thoracic radiotherapy ≤28 days or palliative radiation ≤14 days prior to the first dose of study treatment
   3. Anticancer immunotherapy ≤28 days prior to the first dose of study treatment
   4. Major surgery (excluding placement of vascular access) ≤28 days prior to the first dose of study treatment.
3. Have any unresolved toxicity of Grade ≥2 from previous anticancer treatment, except for Grade 2 alopecia or skin pigmentation. Patients with other chronic but stable Grade 2 toxicities may be allowed to enroll after agreement between the investigator and Sponsor.
4. Past medical history of interstitial lung disease, treatment-related pneumonitis (any grade), or evidence of clinically active interstitial lung disease.

5. Impaired cardiac function or clinically significant cardiac disease including any of the following:

   1. History of congestive heart failure (CHF) Class III/IV according to the New York Heart Association (NYHA) Functional Classification (Appendix A)
   2. Serious cardiac arrhythmias requiring treatment.
   3. Resting corrected QT interval (QTc) >470 msec using Fridericia's formula (QTcF).
6. Is unable to swallow tablets/capsules or has any disease or condition that may significantly affect gastrointestinal absorption of zipalertinib (eg, inflammatory bowel disease, malabsorption syndrome, or prior gastric/bowel resection).

7. 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:

   1. Adequately treated basal or squamous cell carcinoma of the skin
   2. Cancer of the breast or cervix in situ
   3. Patients 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
   4. Patients with concurrent malignancy clinically stable and not requiring tumor-directed treatment
8. Known history of hepatitis B, hepatitis C, or human immunodeficiency virus (HIV) that is not controlled with treatment.
9. History of COVID-19 infection within 4 weeks prior to enrolment and/or has persistent clinically significant pulmonary symptoms related to prior COVID-19 infection.
10. Active bleeding disorders.
11. Known hypersensitivity to the ingredients in zipalertinib or any drugs similar in structure or class.
12. Is pregnant or lactating.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort A ("prior ex20ins treatment"); Cohort A ("prior ex20ins treatment") participants will receive zipalertinib orally twice a day (BID) continuously until documentation of PD or until other withdrawal criteria are met, whichever comes first.	Drug: TAS6417; Oral tablets/capsules; Other Names: CLN-081; zipalertinib
Experimental: Cohort B ("1st line treatment"); Cohort B participants will receive zipalertinib orally twice a day (BID) continuously until documentation of PD or until other withdrawal criteria are met, whichever comes first.	Drug: TAS6417; Oral tablets/capsules; Other Names: CLN-081; zipalertinib
Experimental: Cohort C ("active brain mets"); Cohort C participants will receive zipalertinib orally twice a day (BID) continuously until documentation of PD or until other withdrawal criteria are met, whichever comes first.	Drug: TAS6417; Oral tablets/capsules; Other Names: CLN-081; zipalertinib
Experimental: Cohort D ("other uncommon EGFRmt").; Cohort D participants will receive zipalertinib orally twice a day (BID) continuously until documentation of PD or until other withdrawal criteria are met, whichever comes first.	Drug: TAS6417; Oral tablets/capsules; Other Names: CLN-081; zipalertinib

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
All Cohorts: objective response rate (ORR)	Up to approximately 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival (PFS)		Up to approximately 2 years
All Cohorts: The rate and severity of treatment emergent AEs		Up to approximately 2 years
All Cohorts: Overall Survival (OS)	Antitumor activity is assessed by response evaluation criteria RECIST 1.1 by measuring	Up to approximately 2 years
All Cohorts: Disease control rate (DCR)		Up to approximately 2 years
All Cohorts: Duration of response (DoR)		Up to approximately 2 years
Cohort C: Intracranial (i) Overall Response Rate (iORR)		Up to approximately 2 years
Cohort C: intracranial duration of complete response (iDCR)		Up to approximately 2 years
Cohort C: intracranial duration of Response (iDoR)		Up to approximately 2 years
All Cohorts: Pharmacokinetic (PK) parameter	Minimum Plasma Concentration (Cmin)	Up to approximately 2 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetic (PK) parameter	Minimum Plasma Concentration [Cmin]	Up to approximately 2 years
Pharmacokinetic (PK) parameter	Maximum Plasma Concentration [Cmax]	Up to approximately 2 years
Pharmacokinetic (PK) parameter	Area Under Curve [AUC]	Up to approximately 2 years
EGFR mutation status	Local central tests results	Up to approximately 2 years

Collaborators and Investigators

• Sponsor: Taiho Oncology, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): July 27, 2023
• Primary Completion (Estimated): June 30, 2025
• Study Completion (Estimated): October 20, 2025

Study Registration Dates

• First Submitted: July 11, 2023
• First Submitted That Met QC Criteria: July 21, 2023
• First Posted (Actual): August 1, 2023

Study Record Updates

• Last Update Posted (Estimated): February 29, 2024
• Last Update Submitted That Met QC Criteria: February 28, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: NSCLC; Carcinoma; Lung disease; Non-Small Cell Lung; locally advanced/ metastatic; ex20ins mutation; Insertion Mutations; EGFR uncommon/ single mutation Phase 2, Phase 2b, Phase II Exon 20; TAS6417/ CLN-081
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
• Other Study ID Numbers: TAS6417-201; 2023-503865-48 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No