REZILIENT3 (REsearching ZIpaLertinib In Egfr Non-small Cell Lung Cancer Tumors)
NCT ID: NCT05973773
Last Updated: 2025-10-31
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
RECRUITING
PHASE3
272 participants
INTERVENTIONAL
2023-06-30
2027-05-27
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
Related Clinical Trials
Explore similar clinical trials based on study characteristics and research focus.
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.
NCT05967689
A Study to Assess the Efficacy and Safety of Zipalertinib Versus Placebo for Adjuvant Treatment in Participants With Stage IB-IIIA NSCLC With Uncommon EGFR Mutations, Following Complete Tumor Resection
NCT07128199
Phase 2 Study of Poziotinib in Participants With NSCLC Having EGFR or HER2 Exon 20 Insertion Mutation
NCT03318939
A Study of Repotrectinib Versus Crizotinib in Participants With Locally Advanced or Metastatic Tyrosine Kinase Inhibitor (TKI)-naïve ROS1-positive Non-Small Cell Lung Cancer (NSCLC) (TRIDENT-3)
NCT06140836
SI-B001 Combined With Osimertinib Mesylate Tablets in the Treatment of Recurrent Metastatic Non-small Cell Lung Cancer.
NCT05020769
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
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. Patients randomized to the chemotherapy-only treatment arm in Part B may receive treatment with zipalertinib as monotherapy after BICR-assessed progressive disease (PD) is documented (optional "crossover arm").
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 260 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.
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
RANDOMIZED
SEQUENTIAL
TREATMENT
NONE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
Part A (Safety Lead in)
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.
TAS6417
oral tablets
Part B
Enrollment into the Phase 3 portion of the study will begin following completion of Part A.
Approximately 260 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.
TAS6417
oral tablets
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
TAS6417
oral tablets
Other Intervention Names
Discover alternative or legacy names that may be used to describe the listed interventions across different sources.
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
2. ≥18 years of age (or meets the country's regulatory definition for legal adult age, whichever is greater).
3. Pathologically confirmed, locally advanced or metastatic nonsquamous NSCLC
4. Has not received any prior systemic treatment for their locally advanced or metastatic nonsquamous NSCLC. Prior adjuvant/neoadjuvant treatment received \>6 months prior to first dose of study treatment is allowed for early-stage
NSCLC. Prior monotherapy with an approved EGFR TKI (ie, gefitinib, erlotinib, afatinib, dacomitinib, or osimertinib) as nonstandard first-line therapy for the treatment of locally advanced or metastatic disease is allowed if all of the following criteria are met:
1. Treatment duration did not exceed 8 weeks;
2. Lack of disease response was documented (radiographically) by an increase in tumor burden (a copy of the computerized tomography \[CT\] report showing increase in tumor burden from baseline should be submitted);
3. Associated toxicities have resolved to baseline; and
4. The EGFR TKI was discontinued at least 2 weeks or 4 half-lives prior to randomization, whichever is longer.
Prior therapy with EGFR TKI agents targeting exon20ins mutations including amivantamab, mobocertinib, sunvozertinib, furmonertinib, and poziotinib is not allowed.
5. Documented EGFR mutation status, as determined by local testing performed at a CLIA certified (US) or accredited (outside of the US) local laboratory, defined as follows:
1. Part A: EGFR ex20ins or other uncommon single or compound EGFR mutation
2. Part B: EGFR ex20ins mutation
6. Archival tumor tissue available for submission, with minimum quantity sufficient to evaluate EGFR mutation status and, where possible, other biomarkers. Patients with insufficient tissue (details provided in laboratory manual) may be eligible following discussion with the sponsor; a fresh biopsy will not be required.
7. Patients with brain metastasis(es) who have previously received definitive local treatment and have stable central nervous system (CNS) disease (defined as being neurologically stable and off corticosteroid for at least 2 weeks prior to enrollment) are eligible. If brain metastases are diagnosed on screening imaging, the patient may be rescreened for eligibility after definitive treatment.
b. Asymptomatic brain metastases ≤2 cm in size can be eligible for inclusion if, in the opinion of the Investigator, immediate definitive treatment is not indicated.
8. At least one measurable lesion as determined per RECIST 1.1 for patients enrolling to Part B. Patients enrolling to Part A may be enrolled without measurable disease.
9. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
10. Adequate organ function, as defined by the laboratory value
11. Have a life expectancy of at least 3 months as assessed by the investigator.
12. 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 postmenopausal (no menses for 12 months without an alternative medical cause) or permanently sterile (hysterectomy, bilateral salpingectomy, or bilateral oophorectomy).
13. Both males and females of reproductive potential must agree to use effective birth control during the study prior to the first dose and for 6 months after the last dose of study treatment or longer, based on local requirements.
Exclusion -
1. Is 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.
2. Prior treatment with any of the following within the specific time frame specified:
1. Zipalertinib (TAS6417/CLN-081) at any time.
2. Thoracic radiotherapy ≤28 days, palliative radiation of nonthoracic disease ≤14 days, or palliative radiation of a single lesion ≤7 days prior to first dose of study treatment.
3. Major surgery (excluding placement of vascular access) ≤28 days prior to first dose of study treatment.
4. All prescribed medication, over-the-counter medication, vitamin preparations and other food supplements, or herbal medications that are strong or moderate CYP3A4 inducers or inhibitors within 7 days prior to first dose.
3. Have any unresolved toxicity of Grade ≥2 from previous anticancer treatment in the neoadjuvant or adjuvant setting, 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 any 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 .
2. Serious cardiac arrhythmias requiring treatment.
3. Resting corrected QT interval (QTc) \>470 msec calculated using Fridericia's formula (QTcF).
6. 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 GI 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. Previously treated malignancy, if all treatment for that malignancy was completed at least 2 years prior to first dose of study treatment, and no current evidence of disease
4. Concurrent malignancy determined to be clinically stable and not requiring tumor directed treatment
8. Known history of hepatitis B, hepatitis C, or human immunodeficiency virus (HIV) that is unstable or not controlled with treatment.
9. History of COVID-19 infection within 4 weeks prior to enrolment and/or have 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. To platinum-containing drugs (ie, cisplatin, carboplatin), pemetrexed, or any known excipients of these drugs. b. Contraindications toning drugs (ie, cisplatin, carboplatin) or pemetrexed according to the respective local labels.
12. History of leptomeningeal disease and spinal cord compression.
13. Is unable or unwilling to take dexamethasone, folic acid, and/or vitamin B12 supplementation during treatment with pemetrexed.
14. Is pregnant or lactating or planning to become pregnant
15. The patient is, in the investigator's opinion, unable or unwilling to comply with the trial procedures.
18 Years
ALL
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
Taiho Oncology, Inc.
INDUSTRY
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
Comprehensive Cancer Centers of Nevada - Henderson
Henderson, Nevada, United States
Comprehensive Cancer Centers of Nevada - Horizon Ridge Henderson
Henderson, Nevada, United States
Comprehensive Cancer Centers of Nevada - Southeast Henderson - Stephanie
Henderson, Nevada, United States
Comprehensive Cancer Centers of Nevada - Summerlin Medical Center II
Las Vegas, Nevada, United States
Comprehensive Cancer Centers of Nevada - Southwest
Las Vegas, Nevada, United States
Comprehensive Cancer Centers of Nevada - Central Valley - Twain
Las Vegas, Nevada, United States
Comprehensive Cancer Centers of Nevada - Northwest
Las Vegas, Nevada, United States
Gabrail Cancer and Research Center
Canton, Ohio, United States
The Toledo Clinic Cancer Center
Toledo, Ohio, United States
University of Texas MD Anderson Cancer Center
Houston, Texas, United States
Universitair Ziekenhuis Leuven - Campus Gasthuisberg
Leuven, Flemish Brabant, Belgium
Algemeen Ziekenhuis Maria Middelares
Ghent, Oost-Vlaaderen, Belgium
Algemeen Ziekenhuis Delta - Campus Menen
Menen, West Flanders, Belgium
Algemeen Ziekenhuis Delta - Campus Rumbeke
Rosières, West-Vlaanderen, Belgium
Centro Regional Integrado de Oncologia
Fortaleza, Ceará, Brazil
Hospital Mãe de Deus - Centro Integrado de Oncologia
Porto Alegre, Rio Grande do Sul, Brazil
Hospital São Lucas da PUCRS
Porto Alegre, Rio Grande do Sul, Brazil
Clínica Neoplasias Litoral
Itajaí, Santa Catatina, Brazil
Hospital Amaral Carvalho
Jaú, São Paulo, Brazil
Multi-profile Hospital for Active Treatment Uni Hospital
Panagyurishte, Pazardzhik, Bulgaria
University Multiprofile Hospital for Active Treatment Tsaritsa Yoanna-ISUL
Sofia, , Bulgaria
BC Cancer Vancouver
Vancouver, British Columbia, Canada
William Osler Health System - Brampton Civic Hospital
Brampton, Ontario, Canada
Princess Margaret Cancer Centre
Toronto, Ontario, Canada
CentroEstudiosClinicosSAGA
Santiago, Region de Santiago, Chile
Hospital Clínico Universidad de Chile
Independencia, Santiago Metropolitan, Chile
Instituto Oncológico Fundación Arturo López Pérez
Providencia, Santiago Metropolitan, Chile
Les Hôpitaux Universitaires de Strasbourg
Strasbourg, Alsace, France
Hôpital Côte De Nacre
Caen, Basse-Normandie, France
Centre Hospitalier Universitaire Limoges
Limoges, Limousin, France
Hôpital Haut-Lévêque
Pessac, Nouvelle-Aquitaine, France
Centre Hospitalier Le Mans
Le Mans, Pays de la Loire Region, France
Gustave Roussy
Villejuif, Val-de-Marne, France
CH Cornouaille Quimper
Quimper, , France
Hôpital Ambroise-Paré
Boulogne-Billancourt, Île-de-France Region, France
Institut Curie
Paris, Île-de-France Region, France
Asklepios Klinik Altona
Hamburg, Hamburg (Hansestadt), Germany
Universitätsklinikum Gießen und Marburg - Gießen
Giessen, Hesse, Germany
LMU Klinikum - Campus Innenstadt
München, , Germany
Universitätsklinikum Regensburg
Regensburg, , Germany
General Hospital for Thoracic Diseases Sotiria
Athens, Attica, Greece
Metropolitan General
Piraeus, Attica, Greece
University General Hospital of Patras
Patra, Peloponnese, Greece
Metropolitan Hospital
Piraeus, Pireas, Greece
University General Hospital of Larissa
Larissa, Thessaly, Greece
BioClinic Thessaloniki
Thessaloniki, , Greece
Emek Medical Center
Afula, , Israel
Shaare Zedek Medical Center
Jerusalem, , Israel
Hadassah University Hospital Ein Kerem
Jerusalem, , Israel
Tel Aviv Sourasky Medical Center
Tel Aviv, , Israel
Assuta Hospital - Ramat HaHayal
Tel Aviv, , Israel
Istituto Romagnolo per lo Studio dei Tumori "Dino Amadori" - IRST
Meldola, Forli-Cesena, Italy
Istituto Romagnolo per lo Studio dei Tumori "Dino Amadori" - IRST
Meldola, Forlì-Cesena, Italy
Istituto Nazionale per la Ricerca sul Cancro
Genova, Genoa, Italy
Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) - Ospedale San Raffaele
Milan, , Italy
Azienda Ospedaliero - Universitaria di Modena
Modena, , Italy
Fondazione IRCCS Policlinico San Matteo
Pavia, , Italy
Azienda Unità Sanitaria Locale della Romagna
Ravenna, , Italy
IRCCS Istituto Nazionale Tumori Regina Elena
Roma, , Italy
Azienda Ospedaliera Universitaria Integrata Verona
Verona, , Italy
Aichi Cancer Center
Nagoya, Aiti [Aichi], Japan
Hirosaki University Hospital
Hirosaki-Shi, Aomori, Japan
Kyushu Cancer Center
Fukuoka, Hukuoka, Japan
Kitasato University Hospital
Sagamihara, Kanagawa, Japan
Kanagawa Cardiovascular and Respiratory Center
Yokohama, Kanagawa, Japan
Saiseikai Kumamoto Hospital
Kumamoto, Kumamoto, Japan
Sendai Kousei Hospital
Sendai, Miyagi, Japan
Okayama University Hospital
Okayama, Okayama-ken, Japan
Kansai Medical University Hospital
Hirakata, Osaka, Japan
National Hospital Organization Kinki-Chuo Chest Medical Center
Sakai-Shi, Osaka, Japan
Cancer Institute Hospital of JFCR
Koto, Tokyo, Japan
Keio University Hospital
Shinjuku-Ku, Tokyo, Japan
Kanazawa University Hospital
Kanazawa, , Japan
Osaka City General Hospital
Osaka, , Japan
Osaka Prefectural Hospital Organization - Osaka International Cancer Institute
Osaka, , Japan
Antiguo Hospital Civil de Guadalajara "Fray Antonio Alcalde"
Guadalajara, Jalisco, Mexico
Actualidad Basada en la Investigación del Cáncer
Guadalajara, Jalisco, Mexico
Health Pharma Professional Research S.A. De C.V
Mexico City, Mexico City, Mexico
Clínica Integral Internacional de Oncología S de RL de CV
Mirador, Puebla, Mexico
Investigacion Medica Galerias
Aguascalientes, , Mexico
FAICIC Clínical Research
Veracruz, , Mexico
Radboud Universitair Medisch Centrum
Nijmegen, Gelderland, Netherlands
Antoni Van Leeuwenhoek Ziekenhuis
Amsterdam, North Holland, Netherlands
Vrije Universiteit Medisch Centrum
Amsterdam, North Holland, Netherlands
St. Luke's Medical Center - Quezon City
Quezon City, Metropolitan Manila, Philippines
The Medical City
Pasig, National Capital Region, Philippines
Asian Hospital and Medical Center
City of Muntinlupa, , Philippines
Wielkopolskie Centrum Pulmonologii i Torakochirurgii im. Eugenii i Janusza Zeylandów
Pozna?, Greater Poland Voivodeship, Poland
Samodzielny Publiczny Szpital Kliniczny Nr 4 w Lublinie
Lublin, Lublin Voivodeship, Poland
Instytut MSF
Lodz, Lódzkie, Poland
Medisprof
Cluj-Napoca, Cluj, Romania
Centrul de Oncologie Sf Nectarie
Craiova, Dolj, Romania
Oncocenter - Oncologie Clinica
Timișoara, Timiș County, Romania
Clinica SIGMedical
Suceava, , Romania
National Cancer Centre Singapore
Singapore, , Singapore
Icon Cancer Centre - Mount Alvernia
Singapore, , Singapore
Tan Tock Seng Hospital
Singapore, , Singapore
Oncocare Cancer Centre
Singapore, , Singapore
Icon Cancer Centre Mount Elizabeth
Singapore, , Singapore
Seoul National University Bundang Hospital
Seongnam-si, Gyeonggi-do, South Korea
Catholic University of Korea Saint Vincent's Hospital
Suwon, Gyeonggi-do, South Korea
Ajou University Hospital
Suwon, Gyeonggi-do, South Korea
Gyeongsang National University Hospital
Jinju, Gyeongsangnamdo [Kyongsangnam-do], South Korea
Inha University Hospital
Incheon, Incheon Gwang'yeogsi [Inch'on-Kwangyokshi], South Korea
Korea University Anam Hospital
Seoul, Seoul Teugbyeolsi [Seoul-T'ukpyolshi], South Korea
Korea University Guro Hospital
Seoul, Seoul Teugbyeolsi [Seoul-T'ukpyolshi], South Korea
Complejo Hospitalario Universitario A Coruña
A Coruña, La Coruña, Spain
Clínica Mi Tres Torres
Barcelona, , Spain
Hospital Quirónsalud Barcelona
Barcelona, , Spain
Hospital Clinic de Barcelona
Barcelona, , Spain
Hospital Universitario de Jaén
Jaén, , Spain
MD Anderson Cancer Center Madrid
Madrid, , Spain
Hospital Universitario Fundación Jiménez Díaz
Madrid, , Spain
Hospital Universitario 12 de Octubre
Madrid, , Spain
Hospital Universitario La Paz
Madrid, , Spain
Hospital Regional Universitario de Málaga - Hospital General
Málaga, , Spain
Faculty of Medicine Siriraj Hospital
Bang Phlat, Bangkok, Thailand
King Chulalongkorn Memorial Hospital
Pathum Wan, Bangkok, Thailand
Navamindradhiraj University - Faculty of Medicine Vajira Hospital
Bangkok, Khet Dusit, Thailand
T.C. Saglik Bakanligi Adana Sehir Egitim ve Arastirma Hastanesi
Adana, , Turkey (Türkiye)
Medical Park Seyhan Hastanesi
Adana, , Turkey (Türkiye)
Hacettepe Üniversitesi Kanser Enstitüsü
Ankara, , Turkey (Türkiye)
Memorial Ankara Hastanesi
Ankara, , Turkey (Türkiye)
T.C. Saglik Bakanligi Ankara Bilkent Sehi?r Hastanesi?
Çankaya, , Turkey (Türkiye)
Trakya Üniversitesi Sa?l?k Ara?t?rma ve Uygulama Merkezi
Edirne, , Turkey (Türkiye)
Ankara Il Saglik Mudurlugu SBU Gulhane Egitim Ve Arastirma Hastanesi
Etlik, , Turkey (Türkiye)
Bagcilar Medipol Mega Universite Hastanesi
Istanbul, , Turkey (Türkiye)
T.C. Saglik Bakanligi - Istanbul Il Saglik Mudurlugu - Goztepe Prof. Dr. Suleyman Yalcin Sehir Hastanesi
Istanbul, , Turkey (Türkiye)
Royal Free London NHS Foundation Trust
London, England, United Kingdom
Nottingham University Hospitals NHS Trust
Nottingham, England, United Kingdom
Torbay and South Devon NHS Foundation Trust
Torquay, England, United Kingdom
Countries
Review the countries where the study has at least one active or historical site.
Central Contacts
Reach out to these primary contacts for questions about participation or study logistics.
References
Explore related publications, articles, or registry entries linked to this study.
Heymach JV, Yu HA, Besse B, Cheng Y, Tan DS, Wei L, Wacheck V, Nishio M. REZILIENT3: randomized phase III study of first-line zipalertinib plus chemotherapy in patients with EGFR exon 20 insertion-mutated NSCLC. Future Oncol. 2025 Feb;21(5):549-556. doi: 10.1080/14796694.2025.2457294. Epub 2025 Feb 16.
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
2023-503575-21
Identifier Type: EUDRACT_NUMBER
Identifier Source: secondary_id
TAS6417-301
Identifier Type: -
Identifier Source: org_study_id
More Related Trials
Additional clinical trials that may be relevant based on similarity analysis.