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 | Recruiting Phase 2 FDA Drug

• 2 other identifiers: TAS6417-2012023-503865-48
• Study Type: interventional
• Target: 220
• Locations: 12 countries
• Sites: 80

Brief Summary

The purpose of this study is to evaluate the safety, efficacy and pharmacokinetics (PK) of zipalertinib in participants with locally advanced or metastatic Non-Small Cell Lung Cancer (NSCLC) harboring EGFR ex20ins mutations and other mutations.

Conditions

Advanced or Metastatic NSCLC Harboring Epidermal Growth Factor Receptor (EGFR) Exon 20 Insertion (ex20ins) Mutations

Keywords

NSCLC; Carcinoma; Non-Small Cell Lung; Lung disease; locally advanced/ metastatic; ex20ins mutation; Insertion Mutations; EGFR uncommon/ single mutation Phase 2, Phase 2b, Phase II Exon 20; TAS6417/ CLN-081

Outcome Measures

Primary Outcomes (2)

• Cohorts 1-4: Objective Response Rate (ORR)

  Up to approximately 2 years

• Dose Optimization Substudy: ORR as Assessed by Blinded Independent Central Review (BICR)

  Up to approximately 2 years

Secondary Outcomes (29)

• Cohorts 1-4: Number of Participants With Treatment Emergent Adverse Events (TEAEs) Graded According to the National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (CTCAE v5.0)

  Up to approximately 2 years

• Cohorts 1-4: Number of Participants with Clinically Significant Changes in Clinical Laboratory Parameters

  Up to approximately 2 years

• Cohorts 1-4: Number of Participants with Clinically Significant Changes in Vital Signs

  Up to approximately 2 years

• Cohorts 1-4: Number of Participants with Clinically Significant Changes in Electrocardiogram (ECG) Parameters

  Up to approximately 2 years

• Cohorts 1-4: Number of participants With Change in Left Ventricular Ejection Fraction (LVEF) Evaluated Using Electrocardiography (ECHO) and Multigated Acquisition (MUGA) Scan

  Up to approximately 2 years

Study Arms (8)

Cohort A ("prior ex20ins treatment")

EXPERIMENTAL

Cohort A ("prior ex20ins treatment") participants will receive zipalertinib orally twice a day (BID) continuously until documentation of progressive disease (PD) or until other withdrawal criteria are met, whichever comes first.

Drug: TAS6417

Cohort B ("first-line treatment")

EXPERIMENTAL

Cohort B participants will receive zipalertinib orally, BID continuously until documentation of PD or until other withdrawal criteria are met, whichever comes first.

Drug: TAS6417

Cohort C ("active brain mets")

EXPERIMENTAL

Cohort C participants will receive zipalertinib orally, BID continuously until documentation of PD or until other withdrawal criteria are met, whichever comes first.

Drug: TAS6417

Cohort D ("other uncommon EGFRmts").

EXPERIMENTAL

Cohort D participants will receive zipalertinib orally, BID continuously until documentation of PD or until other withdrawal criteria are met, whichever comes first.

Drug: TAS6417

DDI Substudy: CYP Cocktail Group

EXPERIMENTAL

Participants will receive a single dose of CYP enzyme probe substrates (CYP cocktail) alone prior to the start of zipalertinib dosing and a single dose of CYP cocktail in combination with zipalertinib at steady state. Zipalertinib will be dosed, orally BID in Cycle 1 (cycle length = 21 days), followed by continuous treatment with zipalertinib until documentation of PD or until other withdrawal criteria are met, whichever comes first.

Drug: TAS6417; Drug: CYP Cocktail

DDI Substudy: Transporter Cocktail Group

EXPERIMENTAL

Participants will receive a single dose of transporter probe substrates (Transporter cocktail) alone prior to the start of zipalertinib dosing and a single dose of Transporter cocktail in combination with zipalertinib at steady state. Zipalertinib will be dosed, orally BID in Cycle 1 (cycle length = 21 days), followed by continuous treatment with zipalertinib until documentation of PD or until other withdrawal criteria are met, whichever comes first.

Drug: TAS6417; Drug: Transporter Cocktail

Dose Optimization Substudy: Arm A

EXPERIMENTAL

Participants will receive zipalertinib, orally, at Arm A dose, BID, continuously in 21-day treatment cycles until the participant meets any of the treatment discontinuation criteria.

Drug: TAS6417

Dose Optimization Substudy: Arm B

EXPERIMENTAL

Participants will receive zipalertinib, orally, at Arm B dose, BID, continuously in 21-day treatment cycles until the participant meets any of the treatment discontinuation criteria.

Drug: TAS6417

Interventions

Transporter Cocktail DRUG

Single dose of transporter probe substrates (Transporter cocktail) alone prior to the start of zipalertinib dosing and a single dose of Transporter cocktail in combination with zipalertinib at steady state.

DDI Substudy: Transporter Cocktail Group

TAS6417 DRUG

Oral tablets

Also known as: CLN-081, zipalertinib

Cohort A ("prior ex20ins treatment"); Cohort B ("first-line treatment"); Cohort C ("active brain mets"); Cohort D ("other uncommon EGFRmts").; DDI Substudy: CYP Cocktail Group; DDI Substudy: Transporter Cocktail Group; Dose Optimization Substudy: Arm A; Dose Optimization Substudy: Arm B

CYP Cocktail DRUG

Single dose of CYP enzyme probe substrates (CYP cocktail) alone prior to the start of zipalertinib dosing and a single dose of CYP cocktail in combination with zipalertinib at steady state.

DDI Substudy: CYP Cocktail Group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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.
• Has received any of the following within the specific time frame specified:
• Participant has received Zipalertinib (TAS6417/CLN081) at any time
• 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
• Anticancer immunotherapy ≤28 days prior to the first dose of study treatment
• Major surgery (excluding placement of vascular access) ≤28 days prior to the first dose of study treatment.
• Any prior treatment with an EGFR exon20ins- targeted TKI
• Participants with leptomeningeal CNS disease.
• 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.
• Past medical history of interstitial lung disease, treatment-related pneumonitis (any grade), or evidence of clinically active interstitial lung disease.
• Impaired cardiac function or clinically significant cardiac disease including any of the following:
• History of congestive heart failure (CHF) Class III/IV according to the New York Heart Association (NYHA) Functional Classification.
• Serious cardiac arrhythmias requiring treatment.
• Resting corrected QT interval (QTc) \>470 msec using Fridericia's formula (QTcF).
• 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).

Sponsors & Collaborators

• Taiho Oncology, Inc.: lead

Study Sites (80)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

WITHDRAWN

City of Hope - Duarte

Duarte, California, 91010, United States

RECRUITING

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

RECRUITING

Comprehensive Cancer Centers of Nevada - Central Valley - Twain

Las Vegas, Nevada, 89169, United States

RECRUITING

Memorial Sloan Kettering Cancer Center - Basking Ridge

Basking Ridge, New Jersey, 07920, United States

RECRUITING

Memorial Sloan Kettering Cancer Center - Monmouth

Middletown, New Jersey, 07748, United States

RECRUITING

Memorial Sloan Kettering Cancer Center - Bergen

Montvale, New Jersey, 07645, United States

RECRUITING

Memorial Sloan Kettering Cancer Center - Commack

Commack, New York, 11725, United States

RECRUITING

Memorial Sloan Kettering Cancer Center - Westchester

Harrison, New York, 10604, United States

RECRUITING

MSK Cancer Center

Long Island City, New York, 11101, United States

RECRUITING

Memorial Sloan Kettering Cancer Center - Nassau

Uniondale, New York, 11553, United States

RECRUITING

Gabrail Cancer and Research Center

Canton, Ohio, 44718, United States

ACTIVE NOT RECRUITING

Zangmeister Cancer Center

Columbus, Ohio, 43219, United States

WITHDRAWN

The Toledo Clinic Cancer Center

Toledo, Ohio, 43623, United States

WITHDRAWN

SCRI Oncology Partners

Nashville, Tennessee, 37203, United States

RECRUITING

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Virginia Cancer Specialists

Fairfax, Virginia, 22031, United States

RECRUITING

IDS Pharmacy

Milwaukee, Wisconsin, 53226, United States

RECRUITING

Bankstown-Lidcombe Hospital

Bankstown, New South Wales, 2200, Australia

RECRUITING

Genesis Care North Shore

Saint Leonards, New South Wales, 2065, Australia

RECRUITING

Joondalup Hospital Pharmacy

Joondalup, Western Australia, 6027, Australia

RECRUITING

William Osler Health System - Brampton Civic Hospital

Brampton, L6R 3J7, Canada

RECRUITING

Nouvel Hôpital Civil

Strasbourg, Aslace, 67091, France

RECRUITING

Centre Leon Berard

Lyon, Auvergne-Rhône-Alpes, 69008, France

RECRUITING

CHU Caen Normandie

Caen, Basse-Normandie, 14033, France

RECRUITING

Centre Hospitalier Universitaire Limoges

Limoges, Limousin, 87042, France

RECRUITING

Hopital Haut Leveque

Pessac, Nouvelle-Aquitaine, 33604, France

RECRUITING

Hôpital Nord de Marseille

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

RECRUITING

Hopital Nord Laennec

Saint-Herblain, 44800, France

RECRUITING

Hopital Ambroise Pare

Boulogne-Billancourt, Île-de-France Region, 92100, France

RECRUITING

Institut Curie

Paris, Île-de-France Region, 75005, France

RECRUITING

Gesundheit Nordhessen Holding AG

Kassel, Hassen, 34125, Germany

RECRUITING

Uniklinik Dresden

Dresden, 01307, Germany

RECRUITING

UKGM Studienzentrale

Giessen, 35392, Germany

RECRUITING

UKR Innere Med II Pneumologie

Regensburg, 93053, Germany

WITHDRAWN

Queen Mary Hospital

Pok Fu Lam, Hong Kong Island, Hong Kong

ACTIVE NOT RECRUITING

Azienda Ospedaliero - Universitaria Careggi

Florence, Florence, 50134, Italy

RECRUITING

Istituto Romagnolo per lo Studio dei Tumori "Dino Amadori" - IRST

Meldola, Forli-Cesena, 47014, Italy

RECRUITING

Azienda Socio-Sanitaria Territoriale di Cremona

Cremona, 26100, Italy

RECRUITING

Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) - Ospedale San Raffaele

Milan, 20132, Italy

RECRUITING

Azienda Ospedaliero-Universitaria di Parma

Parma, 43126, Italy

RECRUITING

Ospedale S. Maria delle Croci

Ravenna, 48121, Italy

RECRUITING

Aichi Cancer Center

Nagoya, Aichi-ken, 464-8681, Japan

RECRUITING

National Cancer Center Hospital East

Kashiwa-shi, Chiba, 277-8577, Japan

RECRUITING

NHO Kyushu Cancer Center

Fukuoka, Hukuoka, 811-1395, Japan

RECRUITING

Sendai Kousei Hospital

Sendai, Miyagi, 980-0873, Japan

RECRUITING

Niigata Cancer Center Hospital

Niigata, Niigata, 951-8566, Japan

RECRUITING

Kindai University Hospital

Sayama, Osaka, 589-8511, Japan

RECRUITING

Shizuoka Cancer Center

Sunto-gun, Shizuoka, 411-8777, Japan

RECRUITING

National Cancer Center Hospital

Chuo Ku, Tokyo, 104-0045, Japan

RECRUITING

Cancer Institute Hospital of JFCR

Koto-ku, Tokyo, 135-8550, Japan

RECRUITING

Okayama University Hospital

Okayama, 700-8558, Japan

RECRUITING

National Cancer Center - Korea

Goyang-si, Gyeonggi-do, 10408, South Korea

WITHDRAWN

Saint Vincent's Hospital

Suwon, Gyeonggi-do, 16247, South Korea

RECRUITING

Ajou University Hospital

Suwon, Gyeonggi-do, 16499, South Korea

RECRUITING

Gyeongsang National University Hospital

Jinju, Gyeongsangnamdo [Kyongsangnam-do], 52727, South Korea

RECRUITING

Inha University Hospital

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

RECRUITING

Chonnam National University Hwasun Hospital

Hwasun-gun, Jeollanam-do, 58128, South Korea

RECRUITING

Seoul National University Hospital

Seoul, Seoul Teugbyeolsi [Seoul-T'ukpyolshi], 03080, South Korea

ACTIVE NOT RECRUITING

Asan Medical Center

Seoul, Seoul Teugbyeolsi [Seoul-T'ukpyolshi], 05505, South Korea

RECRUITING

Korea University Guro Hospital

Seoul, Seoul Teugbyeolsi [Seoul-T'ukpyolshi], 08308, South Korea

RECRUITING

Seoul St. Mary's Hospital

Soeul, Seoul Teugbyeolsi [Seoul-T'ukpyolshi], 06591, South Korea

WITHDRAWN

Hospital Regional Universitario de Málaga - Hospital General

Málaga, Malaga, 29010, Spain

RECRUITING

UOMi Clinica Mi Tres Torres

Barcelona, 08017, Spain

RECRUITING

Hospital Quirónsalud Barcelona

Barcelona, 08023, Spain

RECRUITING

Hospital Clinic de Barcelona

Barcelona, 08036, Spain

RECRUITING

Complejo Hospitalario de Jaen

Jaén, 23007, Spain

RECRUITING

MD Anderson Cancer Center Madrid

Madrid, 28033, Spain

RECRUITING

Hospital Universitario Fundación Jiménez Díaz

Madrid, 28040, Spain

RECRUITING

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

RECRUITING

Hospital La Paz

Madrid, 28046, Spain

RECRUITING

Istinye Üniversite Hastanesi Liv Hospital Bahcesehir

Esenyurt, Istanbul, 34517, Turkey (Türkiye)

RECRUITING

Medical Park Seyhan Hastanesi

Adana, 01140, Turkey (Türkiye)

RECRUITING

Trakya Üniversitesi Saglik Arastirma ve Uygulama Merkezi

Edirne, 22030, Turkey (Türkiye)

RECRUITING

Bagcilar Medipol Mega Universite Hastanesi

Istanbul, 34214, Turkey (Türkiye)

RECRUITING

Prof. Dr. Suleyman Yalcin Sehir Hastanesi

Istanbul, 34722, Turkey (Türkiye)

RECRUITING

The Royal Free Hospital NHS Foundation Trust

Barnet, England, EN5 3DJ, United Kingdom

RECRUITING

Royal Free London NHS Foundation Trust

London, England, NW3 2QG, United Kingdom

RECRUITING

The Christie NHS Foundation Trust

Manchester, England, M20 4BX, United Kingdom

RECRUITING

Nottingham University Hospitals NHS Trust

Nottingham, England, NG5 1PB, United Kingdom

RECRUITING

MeSH Terms

Conditions

Carcinoma; Lung Diseases

Interventions

zipalertinib

Condition Hierarchy (Ancestors)

Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Respiratory Tract Diseases

Central Study Contacts

Taiho Oncology, INC

CONTACT

+1 844-878-2446; medicalinformation@taihooncology.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 6 Cohorts based on eligibility criteria

Study Record Dates

• First Submitted: July 11, 2023
• First Posted: August 1, 2023
• Study Start: July 31, 2023
• Primary Completion (Estimated): August 31, 2028
• Study Completion (Estimated): December 31, 2028
• Last Updated: March 10, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

GB (4); AU (3); FR (9); DE (4); ES (9); US (18); CA (1); IT (6); KR (10); HK (1); TU (5); JP (10)