New pill shows promise for tough lung cancer mutation

NCT ID NCT05967689

Disease control Sponsor: Taiho Oncology, Inc. Source: ClinicalTrials.gov ↗

First seen Jun 27, 2026 · Last updated Sep 02, 2026 · Updated 2 times

Summary

This phase 2b trial tests an oral drug called zipalertinib in 220 people with advanced non-small cell lung cancer that has certain EGFR mutations. The goal is to see if the drug can shrink tumors and how safe it is. Participants take the drug daily, and researchers will monitor their response and any side effects.

What this could mean

Our plain-language read of the trial. This is informational only, not medical advice or a prediction.

Active substance: zipalertinib (oral tablet)
What this could lead to: If successful, this could provide a new targeted treatment option for people with a hard-to-treat form of lung cancer.
What could go wrong: This is a mid-stage trial, so the drug may not prove effective or safe enough for approval. Side effects are possible, and results may not apply to all patients.

This is an AI summary of the original study and may miss details. Read our disclaimer.

Study facts

What this study's own registry entry says, in plain language.

Phase

Phase 2

Tests whether the treatment actually works, and watches for side effects, in a larger group.

Participants

About 220 people

The number the study aims to enrol. It can still change while the study runs.

Started

Jul 2023

Expected to finish

Dec 2028

An estimate. End dates often move.

Lead sponsor

A company

The lead sponsor is a pharmaceutical, biotech, or medical-device company.

Who can take part

This study's own entry requirements. Only the study team can say for certain whether you qualify.

Ages

18 years and older

Sex

Anyone

Healthy volunteers

Not accepted

This study is not open to healthy volunteers. The entry requirements below say who it is open to.

Show the full entry requirements

Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.

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 participants: * 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. 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. * 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/or 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. Cohort B participants: * 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/neoadjuvant 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/or 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. Cohort C participants: * 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/or progressive brain metastasis(es) measurable by Response Assessment in Neuro-oncology Brain Metastases (RANO-BM) criteria and not subjected to CNS-directed therapy, AND/OR * LMD measurable or non-measurable by RANO-BM criteria and confirmed by a positive cerebrospinal fluid cytology, or unequivocal radiographic and/or 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. Cohort D participants: * 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/or 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/neoadjuvant 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/neoadjuvant 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. DDI Substudy: 1. Participant has pathologically confirmed, locally advanced or metastatic NSCLC: 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: * 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/or 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. Dose Optimization Substudy: 1. Has pathologically confirmed, locally advanced or metastatic NSCLC meeting all the following criteria: 1. Documented EGFR ex20ins status, as determined by local testing performed at a CLIA certified (US) or locally certified laboratory (outside the US) 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. Note: Progression on or after systemic therapy with amivantamab is permitted (eg, given as monotherapy or in combination with chemotherapy). 2. Participants with CNS metastases are eligible if both of the following criteria are met: 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. 3. Measurable disease per RECIST 1.1. 4. Has archival tumor tissue available for submission, with minimum quantity sufficient to evaluate EGFRmt status and, where possible, other biomarkers 5. ECOG PS of 0 or 1. 6. Has adequate organ function. Exclusion Criteria: 1. 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. 2. Has received any of the following within the specific time frame specified: 1. Participant has received Zipalertinib (TAS6417/CLN081) at any time 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 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. 5. Any prior treatment with an EGFR exon20ins- targeted TKI 6. Participants with leptomeningeal CNS disease. 3. 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. 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. 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 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 in situ of the breast or cervix 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 4. Participants 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 Coronavirus disease 2019 (COVID-19) infection within 4 weeks prior to enrollment 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, lactating, or planning to become pregnant. 13. The participant is, in the Investigator's opinion, unable or unwilling to comply with the trial procedures.

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Conditions

The condition(s) this trial relates to.

carcinoma lung disorder non-small cell lung carcinoma

As listed by the trial registrant

The condition terms exactly as the trial's registrant entered them.

Advanced or metastatic NSCLC harboring epidermal growth factor receptor (EGFR) exon 20 insertion (EX20INS) mutations

How to take part

Only the study team decides who joins. These are the ways to reach them.

The study's own enquiry address

This study publishes an address for enquiries. See it below .
The places running it

70 sites in 12 countries. The list below names each one and where it is.
The official record

ClinicalTrials.gov lists the study team's own contact details, including names and phone numbers. We don't republish those.

Open the record ↗
A doctor treating you

A doctor who knows your case can contact a study site on your behalf, and can tell you whether this study is worth pursuing at all.

Contacts and locations

Show contact details

Study contacts

Contact

Email: •••••@•••••

Locations

Aichi Cancer Center
RECRUITING

Nagoya, Aichi-ken, 464-8681, Japan
Ajou University Hospital
RECRUITING

Suwon, Gyeonggi-do, 16499, South Korea
Asan Medical Center
RECRUITING

Seoul, Seoul Teugbyeolsi [Seoul-T'ukpyolshi], 05505, South Korea
Azienda Ospedaliero - Universitaria Careggi
RECRUITING

Florence, Florence, 50134, Italy
Azienda Ospedaliero-Universitaria di Parma
RECRUITING

Parma, 43126, Italy
Azienda Socio-Sanitaria Territoriale di Cremona
RECRUITING

Cremona, 26100, Italy
Bagcilar Medipol Mega Universite Hastanesi
WITHDRAWN

Istanbul, 34214, Turkey (Türkiye)
Bankstown-Lidcombe Hospital
RECRUITING

Bankstown, New South Wales, 2200, Australia
Beth Israel Deaconess Medical Center
RECRUITING

Boston, Massachusetts, 02215, United States
CHU Caen Normandie
RECRUITING

Caen, Basse-Normandie, 14033, France
Cancer Institute Hospital of JFCR
RECRUITING

Koto-ku, Tokyo, 135-8550, Japan
Centre Hospitalier Universitaire Limoges
RECRUITING

Limoges, Limousin, 87042, France
Centre Leon Berard
RECRUITING

Lyon, Auvergne-Rhône-Alpes, 69008, France
Chonnam National University Hwasun Hospital
WITHDRAWN

Hwasun-gun, Jeollanam-do, 58128, South Korea
City of Hope - Duarte
RECRUITING

Duarte, California, 91010, United States
Complejo Hospitalario de Jaen
RECRUITING

Jaén, 23007, Spain
Comprehensive Cancer Centers of Nevada - Central Valley - Twain
RECRUITING

Las Vegas, Nevada, 89169, United States
Gabrail Cancer and Research Center
RECRUITING

Canton, Ohio, 44718, United States
Genesis Care North Shore
RECRUITING

Saint Leonards, New South Wales, 2065, Australia
Gesundheit Nordhessen Holding AG
RECRUITING

Kassel, Hassen, 34125, Germany
Gyeongsang National University Hospital
RECRUITING

Jinju, Gyeongsangnamdo [Kyongsangnam-do], 52727, South Korea
Hopital Ambroise Pare
RECRUITING

Boulogne-Billancourt, Île-de-France Region, 92100, France
Hopital Haut Leveque
RECRUITING

Pessac, New Aquitaine, 33604, France
Hopital Nord Laennec
RECRUITING

Saint-Herblain, 44800, France
Hospital Clinic de Barcelona
RECRUITING

Barcelona, 08036, Spain
Hospital La Paz
RECRUITING

Madrid, 28046, Spain
Hospital Quirónsalud Barcelona
RECRUITING

Barcelona, 08023, Spain
Hospital Regional Universitario de Málaga - Hospital General
RECRUITING

Málaga, Malaga, 29010, Spain
Hospital Universitario 12 de Octubre
RECRUITING

Madrid, 28041, Spain
Hospital Universitario Fundación Jiménez Díaz
RECRUITING

Madrid, 28040, Spain
Hôpital Nord de Marseille
RECRUITING

Marseille, Provence-Alpes-Côte d'Azur Region, 13015, France
IDS Pharmacy
RECRUITING

Milwaukee, Wisconsin, 53226, United States
Inha University Hospital
RECRUITING

Incheon, Incheon Gwang'yeogsi [Inch'on-Kwangyokshi], 22332, South Korea
Institut Curie
RECRUITING

Paris, Île-de-France Region, 75005, France
Istinye Üniversite Hastanesi Liv Hospital Bahcesehir
RECRUITING

Esenyurt, Istanbul, 34517, Turkey (Türkiye)
Istituto Romagnolo per lo Studio dei Tumori "Dino Amadori" - IRST
RECRUITING

Meldola, Forli-Cesena, 47014, Italy
Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) - Ospedale San Raffaele
RECRUITING

Milan, 20132, Italy
Joondalup Hospital Pharmacy
WITHDRAWN

Joondalup, Western Australia, 6027, Australia
Kindai University Hospital
RECRUITING

Sayama, Osaka, 589-8511, Japan
Korea University Guro Hospital
RECRUITING

Seoul, Seoul Teugbyeolsi [Seoul-T'ukpyolshi], 08308, South Korea
MD Anderson Cancer Center Madrid
RECRUITING

Madrid, 28033, Spain
MSK Cancer Center
RECRUITING

Long Island City, New York, 11101, United States
Medical Park Seyhan Hastanesi
RECRUITING

Adana, 01140, Turkey (Türkiye)
Memorial Sloan Kettering Cancer Center - Basking Ridge
RECRUITING

Basking Ridge, New Jersey, 07920, United States
Memorial Sloan Kettering Cancer Center - Bergen
RECRUITING

Montvale, New Jersey, 07645, United States
Memorial Sloan Kettering Cancer Center - Commack
RECRUITING

Commack, New York, 11725, United States
Memorial Sloan Kettering Cancer Center - Monmouth
RECRUITING

Middletown, New Jersey, 07748, United States
Memorial Sloan Kettering Cancer Center - Nassau
RECRUITING

Uniondale, New York, 11553, United States
Memorial Sloan Kettering Cancer Center - Westchester
RECRUITING

Harrison, New York, 10604, United States
NHO Kyushu Cancer Center
RECRUITING

Fukuoka, Hukuoka, 811-1395, Japan
National Cancer Center - Korea
WITHDRAWN

Goyang-si, Gyeonggi-do, 10408, South Korea
National Cancer Center Hospital
RECRUITING

Chuo Ku, Tokyo, 104-0045, Japan
National Cancer Center Hospital East
RECRUITING

Kashiwa-shi, Chiba, 277-8577, Japan
Niigata Cancer Center Hospital
RECRUITING

Niigata, Niigata, 951-8566, Japan
Nottingham University Hospitals NHS Trust
RECRUITING

Nottingham, England, NG5 1PB, United Kingdom
Nouvel Hôpital Civil
WITHDRAWN

Strasbourg, Aslace, 67091, France
Okayama University Hospital
RECRUITING

Okayama, 700-8558, Japan
Ospedale S. Maria delle Croci
RECRUITING

Ravenna, 48121, Italy
Prof. Dr. Suleyman Yalcin Sehir Hastanesi
RECRUITING

Istanbul, 34722, Turkey (Türkiye)
Queen Mary Hospital
RECRUITING

Pok Fu Lam, Hong Kong Island, Hong Kong
Royal Free London NHS Foundation Trust
RECRUITING

London, England, NW3 2QG, United Kingdom
SCRI Oncology Partners
RECRUITING

Nashville, Tennessee, 37203, United States
Saint Vincent's Hospital
RECRUITING

Suwon, Gyeonggi-do, 16247, South Korea
Sendai Kousei Hospital
RECRUITING

Sendai, Miyagi, 980-0873, Japan
Seoul National University Hospital
RECRUITING

Seoul, Seoul Teugbyeolsi [Seoul-T'ukpyolshi], 03080, South Korea
Seoul St. Mary's Hospital
WITHDRAWN

Soeul, Seoul Teugbyeolsi [Seoul-T'ukpyolshi], 06591, South Korea
Shizuoka Cancer Center
RECRUITING

Sunto-gun, Shizuoka, 411-8777, Japan
The Christie NHS Foundation Trust
RECRUITING

Manchester, England, M20 4BX, United Kingdom
The Royal Free Hospital NHS Foundation Trust
RECRUITING

Barnet, England, EN5 3DJ, United Kingdom
The Toledo Clinic Cancer Center
WITHDRAWN

Toledo, Ohio, 43623, United States
Trakya Üniversitesi Saglik Arastirma ve Uygulama Merkezi
RECRUITING

Edirne, 22030, Turkey (Türkiye)
UKGM Studienzentrale
RECRUITING

Giessen, 35392, Germany
UKR Innere Med II Pneumologie
WITHDRAWN

Regensburg, 93053, Germany
UOMi Clinica Mi Tres Torres
RECRUITING

Barcelona, 08017, Spain
Uniklinik Dresden
RECRUITING

Dresden, 01307, Germany
University of Alabama at Birmingham
WITHDRAWN

Birmingham, Alabama, 35294, United States
University of Texas MD Anderson Cancer Center
RECRUITING

Houston, Texas, 77030, United States
Virginia Cancer Specialists
RECRUITING

Fairfax, Virginia, 22031, United States
William Osler Health System - Brampton Civic Hospital
RECRUITING

Brampton, L6R 3J7, Canada
Zangmeister Cancer Center
WITHDRAWN

Columbus, Ohio, 43219, United States