Clinical trial • Phase III • Oncology

ZIPALERTINIB for Non-small cell lung cancer|Uncommon EGFR-mutated non-small cell lung cancer

Phase III trial of ZIPALERTINIB for Non-small cell lung cancer|Uncommon EGFR-mutated non-small cell lung cancer.

Overview

Trial Therapeutic Area
Oncology
Trial Disease
Non-small cell lung cancer|Uncommon EGFR-mutated non-small cell lung cancer
Trial Stage
Phase III
Drug Modality
Small molecule

Key dates

Initial CTIS Submission Date
20-06-2025
First CTIS Authorization Date
06-10-2025

Trial design

Randomised, placebo (zipalertinib placebo tablets) plus adjuvant chemotherapy. auxiliary chemotherapy agents listed include pemetrexed (product info: max daily 500 mg/m2), cisplatin (product info: max daily 75 mg/m2), carboplatin (product info: max daily 750 mg); specific schedule not provided in the summary documents.-controlled Phase III trial in Germany, Italy, Poland and others.

Randomised
Yes
Comparator
Placebo (Zipalertinib Placebo Tablets) plus adjuvant chemotherapy. Auxiliary chemotherapy agents listed include Pemetrexed (product info: max daily 500 mg/m2), Cisplatin (product info: max daily 75 mg/m2), Carboplatin (product info: max daily 750 mg); specific schedule not provided in the summary documents.
Target Sample Size
264

Eligibility

Recruits 264 The protocol specifies written informed consent is required. Age inclusion is ≥18 years (adults only). The record flags 'isVulnerablePopulationSelected' = true but no further details on assent/consent handling for minors or other vulnerable groups are provided in the source documents..

Pregnancy Exclusion
Is pregnant or lactating or planning to become pregnant.
Vulnerable Population
The protocol specifies written informed consent is required. Age inclusion is ≥18 years (adults only). The record flags 'isVulnerablePopulationSelected' = true but no further details on assent/consent handling for minors or other vulnerable groups are provided in the source documents.

Inclusion criteria

  • {"criterion_text":"-Provide written informed consent\n-Adequate organ function, as defined: Absolute neutrophil count (ANC) ≥1500/mm3 (≥1.5 × 109/L); Platelets ≥100,000/mm3 (≥100 × 109/L) without platelet transfusion within the last 14 days prior first dose of study treatment; Hemoglobin ≥9.0 g/dL without blood transfusion within 14 days prior first dose of study treatment; Creatinine Clearance ≥50 mL/min (measured or calculated by Cockcroft and Gault equation); Prothrombin Time (PT) ≤1.5 × upper limit of normal (ULN) unless the participant is receiving anticoagulant therapy; Activated Partial Thromboplastin Time (aPTT) OR Partial Thromboplastin Time (PTT) ≤1.5 × ULN unless the participant is receiving anticoagulant therapy; Serum total bilirubin ≤1.5 × ULN OR direct bilirubin ≤ULN for participants with total bilirubin levels >1.5 × ULN or ≤3.0 × ULN for participants with documented Gilbert’s syndrome (unconjugated hyperbilirubinemia); Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) ≤2.5 × ULN\n-Women of child-bearing potential (WOCBP) must have a negative blood-based pregnancy test) within 7 days prior to first dose. Female participants are not considered to be of childbearing potential if they are permanently sterile (hysterectomy, bilateral salpingectomy, or bilateral oophorectomy) or are postmenopausal (no menses for 12 months without an alternative medical cause).\n-Both males and females of reproductive potential must agree to use effective birth control during the study starting prior to the first dose of study treatment and for 1 month after the last dose of zipalertinib/placebo, 6 months after the last dose of chemotherapy, or longer based on local requirements\n-Archival tumor tissue available for submission, with minimum quantity sufficient to evaluate EGFRmt status and, where possible, other biomarkers. Participants with insufficient tissue (details provided in laboratory manual) may be eligible following discussion with the Sponsor.\n-≥18 years of age (or meets the country’s regulatory definition for legal adult age, whichever is greater)\n-Histologically confirmed diagnosis of primary NSCLC on predominantly non-squamous histology\n-Documented EGFRmt status as determined by local testing performed at a clinical laboratory improvement amendments (CLIA) certified (US) or accredited (outside of the US) local laboratory, defined as either one of the following EGFRmt: a. exon20 insertion mutations or b. other uncommon, non-ex20ins EGFRmt (eg, G719X, L861Q, or S768I) Note: Participants may have “compound” EGFRmt as long as the above criteria are met (see Section 2.1. for details) and participants have no EGFRmt qualifying for osimertinib treatment).\n-MRI or CT scan of the brain done prior to surgery. Participants in whom this was not done prior to surgery may still be enrolled if appropriate imaging (ie, MRI or CT of the brain) is performed prior to randomization.\n-Complete surgical resection of the primary NSCLC is mandatory. All gross disease must have been removed at the end of surgery. All surgical margins of resection must be negative for tumor. Resection may be accomplished by open thoracotomy or Video Associated Thoracic Surgery (VATS) techniques.\n-Classified post-operatively as either Stage IB, IIA, IIB, or IIIA according to the TNM staging system for lung cancer (AJCC 9th edition).\n-Complete recovery from surgery at the time of randomization. Treatment cannot commence within 4 weeks following surgery, but no more than 10 weeks may have elapsed between surgery and randomization. Complete post-operative wound healing must have occurred following any surgery.\n-Eastern Cooperative Oncology Group Performance Status of (ECOG PS) 0 or 1."}

Exclusion criteria

  • {"criterion_text":"-If patient currently receiving an investigational drug in a clinical trial or participating in any other type of medical research judged not to be scientifically or medically compatible with this study.\n-Known: a. Hypersensitivity: i. To the ingredients in zipalertinib/placebo or any drugs similar in structure or class. ii. To platinum-containing drugs (ie, cisplatin, carboplatin), pemetrexed, or any known excipients of these drugs. b. Contraindications to platinum-containing drugs (ie, cisplatin, carboplatin) or pemetrexed according to the respective local labels. 11. Is unable or unwilling to take dexamethasone, folic acid, and/or vitamin B12 supplementation during treatment with pemetrexed. 12. Is pregnant or lactating or planning to become pregnant. 13. Judgment by the investigator that the individual should not participate in the study if the individual is unlikely b. Contraindications to platinum-containing drugs (ie, cisplatin, carboplatin) or pemetrexed according to the respective local labels.\n-Is unable or unwilling to take dexamethasone, folic acid, and/or vitamin B12 supplementation during treatment with pemetrexed.\n-Is pregnant or lactating or planning to become pregnant.\n-Judgment by the investigator that the individual should not participate in the study if the individual is unlikely to comply with study procedures, restrictions, and requirements\n-Treatment with any of the following within the time frame specified: a. Zipalertinib (TAS6417/CLN-081) or any other EGFR inhibitor at any time b. Pre-operative or post-operative or planned radiation therapy for the current lung cancer c. ny prior systemic anticancer therapy (eg, neoadjuvant chemotherapy), including investigational therapy, for treatment of NSCLC d. Major surgery (including primary tumor surgery, excluding placement of vascular access) within 4 weeks of the first dose of study treatment e. All prescribed medication, over-the-counter medication, vitamin preparations and other food supplements, or herbal medications that are strong or moderate cytochrome p450 (CYP) 3A4 inducers or inhibitors within 7 days prior to first dose. f. Treatment with an investigational drug within five half-lives of the compound or any of its related material, if known.\n-Has received only segmentectomies or wedge resections\n-Past medical history of ILD/pneumonitis, drug-induced ILD/pneumonitis or any evidence of clinically active ILD/pneumonitis.\n-Impaired cardiac function or clinically significant cardiac disease, including any of the following: a. History of congestive heart failure (CHF) Class III/IV according to the New York b.Serious cardiac arrhythmias requiring treatment c.Mean resting corrected QT interval (QTc) >470 msec obtained from 3 ECGs using Fridericia’s formula (QTcF). d. Any factors that significantly increase the risk of QTc prolongation or risk of arrhythmic events such as congenital long QT syndrome, family history of long QT syndrome, or unexplained sudden death under 40 years of age in first-degree relatives.\n-Unable to swallow tablets or has any disease or condition that may significantly affect gastrointestinal (GI) absorption of zipalertinib (such as inflammatory bowel disease, malabsorption syndrome, or prior significant bowel resection).\n-Participants with a history of any other cancer (except non-melanoma skin cancer or carcinoma in situ of the cervix), with no evidence of disease for >5 years following the end of treatment and which, in the opinion of the treating physician, do not have a substantial risk of recurrence of the prior malignancy.\n-Known history of hepatitis B, hepatitis C, or human immunodeficiency virus (HIV) that is unstable or not controlled with treatment. Screening not required\n-Active bleeding disorders."}

Endpoints

Primary endpoints

  • {"endpoint_text":"-Disease-free survival (DFS) by investigator assessment","definition_or_measurement_approach":"DFS assessed by investigator assessment (as stated: 'by investigator assessment'). No further definition provided in the available summary."}

Recruitment

Digital Remote Recruitment
Yes
Planned Sample Size
264
Recruitment Window Months
62
Consent Approach
Written informed consent is required from each participant (inclusion criterion: 'Provide written informed consent'). Participants must be ≥18 years (or meet country legal adult age). Country-specific informed consent/subject information forms are provided in multiple languages (documents listed include translations/ICFs in German, Italian, Polish, French, Spanish, Dutch, Greek, Romanian and bilingual country-specific versions). No separate assent process for minors is described (minors excluded by age criterion).

Methods

  • Site-based recruitment and HCP outreach — HCP (healthcare professional) letters to referring clinicians (country-specific HCP letters present e.g., Germany, Italy, Poland, Belgium, France, Spain, Netherlands, Romania, Greece).
  • Patient-targeted printed materials — Flyers and patient letters for distribution at sites (country-specific versions listed in documents).
  • Digital outreach — Facebook advertisements and digital outreach materials (country-specific Facebook ads and digital outreach documents exist for Germany, Italy, Poland, Spain, France, Belgium, Netherlands, Romania, Greece).
  • Information webpages / Info website — country-specific info website materials are listed (e.g., Italy, France, Spain).
  • Contact cards — small contact-card materials for some countries (e.g., Romania, Greece).
  • Recruitment procedures (K1/K2) — documented recruitment procedures per country (K1/K2 documents) guiding site-level recruitment processes.

Geography

Total Number Of Sites
99
Total Number Of Participants
141

Germany

Earliest CTIS Part Ii Submission Date
08-10-2025
Latest Decision Or Authorization Date
28-10-2025
Processing Time Days
20
Number Of Sites
4
Number Of Participants
22

Sites

Site Name
Kliniken der Stadt Koeln gGmbH
Department Name
Lungenkrebszentrum Krankenhaus Köln Merheim
Contact Person Name
Birgit Saers
Contact Person Email
saersb@kliniken-koeln.de
Site Name
Krankenhaus Nordwest GmbH
Department Name
Institut Fuer KlinischOnkologische Forschung (IKF)
Contact Person Name
Thorsten Goetze
Contact Person Email
goetze.thorsten@ikf-khnw.de
Site Name
SLK-Kliniken Heilbronn GmbH
Department Name
Fachklinik Loewenstein
Contact Person Name
Jonas Kuon
Contact Person Email
jonas.kuon@slk-kliniken.de
Site Name
Justus-Liebig-Universitaet Giessen
Department Name
Medizinische Klinik IV Organonkologie
Contact Person Name
Thomas Wehler

Italy

Earliest CTIS Part Ii Submission Date
06-10-2025
Latest Decision Or Authorization Date
12-01-2026
Processing Time Days
98
Number Of Sites
23
Number Of Participants
40

Sites

Site Name
Istituto Romagnolo Per Lo Studio Dei Tumori Dino Amadori IRST S.r.l.
Department Name
Unit of Thoracic Oncology
Contact Person Name
Angelo Delmonte
Contact Person Email
angelo.delmonte@irst.emr.it
Site Name
Azienda Ospedaliero-Universitaria Policlinico G. Rodolico-San Marco Di Catania
Department Name
Medical Oncology
Contact Person Name
Hector José Soto Parra
Contact Person Email
hsotoparra.ctu@gmail.com
Site Name
Azienda Unita Sanitaria Locale Della Romagna
Department Name
Ospedale Santa Maria delle Croci U.0. Oncologia, Dipartimento OncoEmatologico
Contact Person Name
Manolo D’Arcangelo
Site Name
ASST Grande Ospedale Metropolitano Niguarda
Department Name
S.C. Oncologia Falck, Niguarda Cancer Centre
Contact Person Name
Diego Signorelli
Site Name
Azienda Socio Sanitaria Territoriale Ovest Milanese
Department Name
Oncology
Contact Person Name
Andrea Luciani
Contact Person Email
andrea.luciani@asst-ovestmi.it

Poland

Earliest CTIS Part Ii Submission Date
10-10-2025
Latest Decision Or Authorization Date
05-12-2025
Processing Time Days
56
Number Of Sites
3
Number Of Participants
6

Sites

Site Name
Warminsko-Mazurskie Centrum Chorob Pluc W Olsztynie
Department Name
Oddział Onkologii z Pododdziałem Chemioterapii
Contact Person Name
Jarosław Kołb-Sielecki
Contact Person Email
j.kolbsielecki@gmail.com
Site Name
Mruk-Med I Sp. z o.o.
Department Name
Not applicable
Contact Person Name
Andrzej Mruk
Contact Person Email
mrukmed@o2.pl
Site Name
4 Wojskowy Szpital Kliniczny Z Poliklinika Samodzielny Publiczny Zaklad Opieki Zdrowotnej We Wroclaw
Department Name
Oddział Onkologii Klinicznej
Contact Person Name
Teresa Zarzycka
Contact Person Email
badaniakliniczne@4wsk.pl

Belgium

Earliest CTIS Part Ii Submission Date
06-10-2025
Latest Decision Or Authorization Date
05-12-2025
Processing Time Days
60
Number Of Sites
3
Number Of Participants
6

Sites

Site Name
Emmaues
Department Name
Department of Pulmonology
Contact Person Name
Annelies Leyssens
Contact Person Email
annelies.leyssens@emmaus.be
Site Name
Universitair Ziekenhuis Antwerpen
Department Name
Thoracic Oncology Unit
Contact Person Name
Reinier Wener
Contact Person Email
reinier.wener@uza.be
Site Name
UZ Leuven
Department Name
Respiratory Oncology Unit
Contact Person Name
Christophe Dooms
Contact Person Email
christophe.dooms@uzleuven.be

France

Earliest CTIS Part Ii Submission Date
13-10-2025
Latest Decision Or Authorization Date
08-12-2025
Processing Time Days
56
Number Of Sites
24
Number Of Participants
26

Sites

Site Name
Centre Hospitalier Intercommunal Creteil
Department Name
Pneumology Department
Contact Person Name
Gaelle Rousseau-Bussac
Site Name
Hopitaux Universitaires Pitie Salpetriere
Department Name
Medical Oncology
Contact Person Name
Baptiste Abbar
Contact Person Email
baptiste.abbar@aphp.fr
Site Name
Les Hopitaux Nord-Ouest
Department Name
Pneumology and thoracic cancerology
Contact Person Name
Lionel Falchero
Contact Person Email
lfalchero@hno.fr
Site Name
Groupe Hospitalier De La Region De Mulhouse Et Sud Alsace
Department Name
Pneumology
Contact Person Name
Didier Debieuvre
Contact Person Email
Debieuvred@ghrmsa.fr
Site Name
Centre Leon Berard
Department Name
Medical Oncology
Contact Person Name
Maurice Perol

Spain

Earliest CTIS Part Ii Submission Date
13-10-2025
Latest Decision Or Authorization Date
15-12-2025
Processing Time Days
63
Number Of Sites
24
Number Of Participants
26

Sites

Site Name
MD Anderson Cancer Center
Department Name
Medical Oncology
Contact Person Name
Fernando Fabio Franco Perez
Contact Person Email
ffranco@fundacionmdanderson.es
Site Name
Hospital Universitario Puerta De Hierro De Majadahonda
Department Name
Medical Oncology
Contact Person Name
Mariano Provencio Pulla
Site Name
Hospital Universitario 12 De Octubre
Department Name
Medical Oncology
Contact Person Name
Jon Zugazagoitia Fraile
Contact Person Email
j.zugazagoitia.imas12@h12o.es
Site Name
Hospital Universitari Vall D Hebron
Department Name
Medical Oncology
Contact Person Name
Alexandre Martínez Martí
Contact Person Email
amartinezmarti@vhio.net
Site Name
Hospital Universitario Y Politecnico La Fe
Department Name
Oncology
Contact Person Name
Oscar Jose Juan Vidal
Contact Person Email
juan_osc@gva.es

Greece

Earliest CTIS Part Ii Submission Date
05-02-2026
Latest Decision Or Authorization Date
05-02-2026
Number Of Sites
5
Number Of Participants
5

Sites

Site Name
Thoracic General Hospital Of Athens I Sotiria
Department Name
Oncology Unit, 3rd Department of Internal Medicine and Laboratory
Contact Person Name
Konstantinos Syrigos
Contact Person Email
ksyrigos.trials@gmail.com
Site Name
Athens Medical Center S.A.
Department Name
4th Departmentof Medical Oncology
Contact Person Name
Ippokratis Korantzis
Contact Person Email
ippokratis.korantzis@gmail.com
Site Name
Metaxa Cancer Center Hospital Of Piraeus
Department Name
Oncology/Inte rnal Medicine Department
Contact Person Name
Evangelos Georgios Fergadis
Contact Person Email
e.fergadis@windowslive.com
Site Name
Saint Savvas Oncology Hospital
Department Name
1 st Medical Oncology Department
Contact Person Name
Alexandros Ardavanis
Contact Person Email
ardavanis@yahoo.com
Site Name
Bioclinic S.A.
Department Name
Oncology Department
Contact Person Name
Ioannis Boukovinas
Contact Person Email
ibouk@otenet.gr

Romania

Earliest CTIS Part Ii Submission Date
09-03-2026
Latest Decision Or Authorization Date
09-03-2026
Number Of Sites
10
Number Of Participants
7

Sites

Site Name
Institutul Oncologic Prof. Dr. Alexandru Trestioreanu Bucuresti
Department Name
Medical Oncology II
Contact Person Name
Alexandru Aurelia
Contact Person Email
auralexandru@yahoo.com
Site Name
Spital Judetean De Urgenta Satu Mare
Department Name
Medical Oncology
Contact Person Name
Luchian Stefan Dan
Contact Person Email
luchiands@gmail.com
Site Name
Memorial Healthcare International S.R.L.
Department Name
Medical Oncology
Contact Person Name
Ingrid Adriana Iordan
Contact Person Email
mireliordan@yahoo.com
Site Name
Radiotherapy Center Cluj S.R.L.
Department Name
Medical Oncology
Contact Person Name
Andrei Ungureanu
Site Name
Oncocenter Oncologie Clinica S.R.L.
Department Name
Oncology Clinica
Contact Person Name
Roxana Ioana Scheusan
Contact Person Email
roxana.scheusan@gmail.com

Netherlands

Earliest CTIS Part Ii Submission Date
06-02-2026
Latest Decision Or Authorization Date
06-02-2026
Number Of Sites
3
Number Of Participants
3

Sites

Site Name
Leids Universitair Medisch Centrum (LUMC)
Department Name
Department of Pulmonary Diseases
Contact Person Name
Egbert Smit
Contact Person Email
E.F.Smit@lumc.nl
Site Name
Radboud universitair medisch centrum Stichting
Department Name
Pulmonary Department
Contact Person Name
Wouter Van Geffen
Site Name
Ziekenhuis St Jansdal
Department Name
Medical oncology
Contact Person Name
Lisenka Boom
Contact Person Email
LN.Boom@stjansdal.nl

Sponsor

Primary sponsor

Full Name
Taiho Oncology Inc.
Organisation Type
Pharmaceutical company
Country Of Registered Address
United States

Contract research organisations

Name
Icon Clinical Research Limited
Responsibilities
Regulatory, operational and sample storage responsibilities (detailed sponsor duties include storage samples and multiple operational codes)
Name
Imperial Clinical Research Services International Ltd.
Responsibilities
Printed materials
Name
Meeting Protocol Worldwide LP
Responsibilities
Patient reimbursement and materials
Name
Medidata Solutions Inc.
Responsibilities
Platform/medidata support (sponsor duties code listed)

Third parties

  • {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"sponsorDuties codes: 7","organisation_type":"Non-Pharmaceutical company"}
  • {"country":"United States","full_name":"Meeting Protocol Worldwide LP","duties_or_roles":"Patient reimbursement and materials","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Life Technologies Clinical Services Lab Inc.","duties_or_roles":"CtDNA/Tumor samples","organisation_type":"Laboratory/Research/Testing facility"}
  • {"country":"United States","full_name":"Icon Laboratory Services Inc.","duties_or_roles":"sponsorDuties code: 4","organisation_type":"Laboratory/Research/Testing facility"}
  • {"country":"United States","full_name":"Llx Solutions LLC","duties_or_roles":"sponsorDuties code: 6","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Suvoda LLC","duties_or_roles":"sponsorDuties code: 3","organisation_type":"Non-Pharmaceutical company"}
  • {"country":"United States","full_name":"Imperial Clinical Research Services International Ltd.","duties_or_roles":"Printed materials","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Icon Medical Imaging","duties_or_roles":"Scan repository","organisation_type":"Laboratory/Research/Testing facility"}
  • {"country":"United States","full_name":"Signant Health Global LLC","duties_or_roles":"Patient Reported Outcomes (PROs)","organisation_type":"Pharmaceutical company"}
  • {"country":"Ireland","full_name":"Icon Clinical Research Limited","duties_or_roles":"Extensive operational responsibilities including sample storage, regulatory and other codes (sponsorDuties codes: 1,12,15,2,3,4,5,8,9) and 'storage samples' listed","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Fisher Clinical Services Inc.","duties_or_roles":"sponsorDuties code: 14","organisation_type":"Pharmaceutical company"}

Investigational products

Investigational Product Name
Zipalertinib
Active Substance
ZIPALERTINIB
Modality
Small molecule
Routes Of Administration
ORAL
Route
ORAL
Authorisation Status
Not authorised (clinical investigational product, prodAuthStatus=1)
Maximum Dose
200 mg (max daily); max total 10400 mg (per product info)
Investigational Product Name
Zipalertinib Placebo Tablets
Modality
Other
Routes Of Administration
ORAL
Route
ORAL
Authorisation Status
Not applicable (placebo)
Investigational Product Name
Pemetrexed (Pemetrexed Fresenius Kabi)
Active Substance
PEMETREXED
Modality
Small molecule
Routes Of Administration
INTRAVENOUS INFUSION
Route
INTRAVENOUS INFUSION
Authorisation Status
Authorised (prodAuthStatus=2; marketing authorisation present)
Maximum Dose
500 mg/m2 (max daily per product info); max total 2000 mg
Investigational Product Name
Cisplatin (Cisplatin Hikma)
Active Substance
CISPLATIN
Modality
Small molecule
Routes Of Administration
INTRAVENOUS INFUSION
Route
INTRAVENOUS INFUSION
Authorisation Status
Authorised (prodAuthStatus=2)
Maximum Dose
75 mg/m2 (max daily per product info); max total 300 mg
Investigational Product Name
Carboplatin (Carboplatin Hikma)
Active Substance
CARBOPLATIN
Modality
Small molecule
Routes Of Administration
INTRAVENOUS INFUSION
Route
INTRAVENOUS INFUSION
Authorisation Status
Authorised (prodAuthStatus=2)
Maximum Dose
750 mg (max daily per product info); max total 3000 mg
Combination Treatment
Yes

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