AzTrials
AzTrials

Advanced or Metastatic NSCLC Harboring Epidermal Growth Factor Receptor (EGFR) Exon 20 Insertion (ex20ins) MutationsPhase 2REZILIENT2NCT05967689

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.

A Phase 2 study testing TAS6417, CYP Cocktail and Transporter Cocktail in people with Advanced or Metastatic NSCLC Harboring Epidermal Growth Factor Receptor (EGFR) Exon 20 Insertion (ex20ins) Mutations, run by Taiho Oncology, Inc. at 80 sites in 12 countries.

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Sites and contacts
Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
TAS6417, CYP Cocktail and Transporter Cocktail
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
220 participants
Where
80 sitesin 12 countries
Study dates
31 Jul 2023to 31 Dec 2028
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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).
  • Measurable disease per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1).
  • 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.
  • Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0 or 17.
  • Adequate organ function, as defined by the hematologic, renal and hepatic laboratory values.
  • 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).
  • 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:
  • Participant has pathologically confirmed, locally advanced or metastatic NSCLC:
  • 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)
  • 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).
  • 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.
  • ECOG PS of 0 or 1.
  • Dose Optimization Substudy:
  • Has pathologically confirmed, locally advanced or metastatic NSCLC meeting all the following criteria:
  • Documented EGFR ex20ins 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 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).
  • Participants with CNS metastases are eligible if both of the following criteria are met:
  • 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.
  • Measurable disease per RECIST 1.1.
  • Has archival tumor tissue available for submission, with minimum quantity sufficient to evaluate EGFRmt status and, where possible, other biomarkers
  • ECOG PS of 0 or 1.
  • Has adequate organ function.

Who cannot join

  • 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.
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  • 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).
  • 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:
  • Adequately treated basal or squamous cell carcinoma of the skin
  • Cancer in situ of the breast or cervix
  • 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
  • Participants with concurrent malignancy clinically stable and not requiring tumor-directed treatment
  • Known history of hepatitis B, hepatitis C, or human immunodeficiency virus (HIV) that is not controlled with treatment.
  • 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.
  • Active bleeding disorders.
  • Known hypersensitivity to the ingredients in zipalertinib or any drugs similar in structure or class.
  • Is pregnant, lactating, or planning to become pregnant.
  • The participant is, in the Investigator's opinion, unable or unwilling to comply with the trial procedures.

Trial locations and contacts

80 sites in 12 countries. Contact the study team or a site near you to ask about taking part.

Taiho Oncology, INC contact

+1 844-878-2446

medicalinformation@taihooncology.com

80 sites in 12 countries

United States18 sites, 14 recruiting

  • Memorial Sloan Kettering Cancer Center - Basking Ridge

    Basking Ridge, New Jersey, 07920

    Recruiting

  • University of Alabama at Birmingham

    Birmingham, Alabama, 35294

    Withdrawn

  • Beth Israel Deaconess Medical Center

    Boston, Massachusetts, 02215

    Recruiting

  • Gabrail Cancer and Research Center

    Canton, Ohio, 44718

    Recruiting

  • Zangmeister Cancer Center

    Columbus, Ohio, 43219

    Withdrawn

  • Memorial Sloan Kettering Cancer Center - Commack

    Commack, New York, 11725

    Recruiting

  • City of Hope - Duarte

    Duarte, California, 91010

    Recruiting

  • Virginia Cancer Specialists

    Fairfax, Virginia, 22031

    Recruiting

  • Memorial Sloan Kettering Cancer Center - Westchester

    Harrison, New York, 10604

    Recruiting

  • University of Texas MD Anderson Cancer Center

    Houston, Texas, 77030

    Recruiting

  • Comprehensive Cancer Centers of Nevada - Central Valley - Twain

    Las Vegas, Nevada, 89169

    Recruiting

  • MSK Cancer Center

    Long Island City, New York, 11101

    Recruiting

  • Memorial Sloan Kettering Cancer Center - Monmouth

    Middletown, New Jersey, 07748

    Recruiting

  • IDS Pharmacy

    Milwaukee, Wisconsin, 53226

    Recruiting

  • Memorial Sloan Kettering Cancer Center - Bergen

    Montvale, New Jersey, 07645

    Recruiting

  • SCRI Oncology Partners

    Nashville, Tennessee, 37203

    Withdrawn

  • The Toledo Clinic Cancer Center

    Toledo, Ohio, 43623

    Withdrawn

  • Memorial Sloan Kettering Cancer Center - Nassau

    Uniondale, New York, 11553

    Recruiting

Other trials in United States

Japan10 sites, 10 recruiting

  • National Cancer Center Hospital

    Chuo Ku, Tokyo, 104-0045

    Recruiting

  • NHO Kyushu Cancer Center

    Fukuoka, Hukuoka, 811-1395

    Recruiting

  • National Cancer Center Hospital East

    Kashiwa-shi, Chiba, 277-8577

    Recruiting

  • Cancer Institute Hospital of JFCR

    Koto-ku, Tokyo, 135-8550

    Recruiting

  • Aichi Cancer Center

    Nagoya, Aichi-ken, 464-8681

    Recruiting

  • Niigata Cancer Center Hospital

    Niigata, Niigata, 951-8566

    Recruiting

  • Okayama University Hospital

    Okayama, 700-8558

    Recruiting

  • Kindai University Hospital

    Sayama, Osaka, 589-8511

    Recruiting

  • Sendai Kousei Hospital

    Sendai, Miyagi, 980-0873

    Recruiting

  • Shizuoka Cancer Center

    Sunto-gun, Shizuoka, 411-8777

    Recruiting

Other trials in Japan

South Korea10 sites, 7 recruiting

  • National Cancer Center - Korea

    Goyang-si, Gyeonggi-do, 10408

    Withdrawn

  • Chonnam National University Hwasun Hospital

    Hwasun-gun, Jeollanam-do, 58128

    Withdrawn

  • Inha University Hospital

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

    Recruiting

  • Gyeongsang National University Hospital

    Jinju, Gyeongsangnamdo [Kyongsangnam-do], 52727

    Recruiting

  • Seoul National University Hospital

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

    Recruiting

  • Asan Medical Center

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

    Recruiting

  • Korea University Guro Hospital

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

    Recruiting

  • Seoul St. Mary's Hospital

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

    Withdrawn

  • Saint Vincent's Hospital

    Suwon, Gyeonggi-do, 16247

    Recruiting

  • Ajou University Hospital

    Suwon, Gyeonggi-do, 16499

    Recruiting

Other trials in South Korea

France9 sites, 8 recruiting

  • Hopital Ambroise Pare

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

    Recruiting

  • CHU Caen Normandie

    Caen, Basse-Normandie, 14033

    Recruiting

  • Centre Hospitalier Universitaire Limoges

    Limoges, Limousin, 87042

    Recruiting

  • Centre Leon Berard

    Lyon, Auvergne-Rhône-Alpes, 69008

    Recruiting

  • Hôpital Nord de Marseille

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

    Recruiting

  • Institut Curie

    Paris, Île-de-France Region, 75005

    Recruiting

  • Hopital Haut Leveque

    Pessac, New Aquitaine, 33604

    Recruiting

  • Hopital Nord Laennec

    Saint-Herblain, 44800

    Recruiting

  • Nouvel Hôpital Civil

    Strasbourg, Aslace, 67091

    Withdrawn

Other trials in France

Spain9 sites, 9 recruiting

  • UOMi Clinica Mi Tres Torres

    Barcelona, 08017

    Recruiting

  • Hospital Quirónsalud Barcelona

    Barcelona, 08023

    Recruiting

  • Hospital Clinic de Barcelona

    Barcelona, 08036

    Recruiting

  • Complejo Hospitalario de Jaen

    Jaén, 23007

    Recruiting

  • MD Anderson Cancer Center Madrid

    Madrid, 28033

    Recruiting

  • Hospital Universitario Fundación Jiménez Díaz

    Madrid, 28040

    Recruiting

  • Hospital Universitario 12 de Octubre

    Madrid, 28041

    Recruiting

  • Hospital La Paz

    Madrid, 28046

    Recruiting

  • Hospital Regional Universitario de Málaga - Hospital General

    Málaga, Malaga, 29010

    Recruiting

Other trials in Spain

Italy6 sites, 6 recruiting

  • Azienda Socio-Sanitaria Territoriale di Cremona

    Cremona, 26100

    Recruiting

  • Azienda Ospedaliero - Universitaria Careggi

    Florence, Florence, 50134

    Recruiting

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

    Meldola, Forli-Cesena, 47014

    Recruiting

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

    Milan, 20132

    Recruiting

  • Azienda Ospedaliero-Universitaria di Parma

    Parma, 43126

    Recruiting

  • Ospedale S. Maria delle Croci

    Ravenna, 48121

    Recruiting

Other trials in Italy

Turkey (Türkiye)5 sites, 4 recruiting

  • Medical Park Seyhan Hastanesi

    Adana, 01140

    Recruiting

  • Trakya Üniversitesi Saglik Arastirma ve Uygulama Merkezi

    Edirne, 22030

    Recruiting

  • Istinye Üniversite Hastanesi Liv Hospital Bahcesehir

    Esenyurt, Istanbul, 34517

    Recruiting

  • Bagcilar Medipol Mega Universite Hastanesi

    Istanbul, 34214

    Withdrawn

  • Prof. Dr. Suleyman Yalcin Sehir Hastanesi

    Istanbul, 34722

    Recruiting

Other trials in Turkey (Türkiye)

Germany4 sites, 3 recruiting

  • Uniklinik Dresden

    Dresden, 01307

    Recruiting

  • UKGM Studienzentrale

    Giessen, 35392

    Recruiting

  • Gesundheit Nordhessen Holding AG

    Kassel, Hassen, 34125

    Recruiting

  • UKR Innere Med II Pneumologie

    Regensburg, 93053

    Withdrawn

Other trials in Germany

United Kingdom4 sites, 4 recruiting

  • The Royal Free Hospital NHS Foundation Trust

    Barnet, England, EN5 3DJ

    Recruiting

  • Royal Free London NHS Foundation Trust

    London, England, NW3 2QG

    Recruiting

  • The Christie NHS Foundation Trust

    Manchester, England, M20 4BX

    Recruiting

  • Nottingham University Hospitals NHS Trust

    Nottingham, England, NG5 1PB

    Recruiting

Other trials in United Kingdom

Australia3 sites, 2 recruiting

  • Bankstown-Lidcombe Hospital

    Bankstown, New South Wales, 2200

    Recruiting

  • Joondalup Hospital Pharmacy

    Joondalup, Western Australia, 6027

    Withdrawn

  • Genesis Care North Shore

    Saint Leonards, New South Wales, 2065

    Recruiting

Other trials in Australia

Canada1 site, 1 recruiting

  • William Osler Health System - Brampton Civic Hospital

    Brampton, L6R 3J7

    Recruiting

Other trials in Canada

Hong Kong1 site, 1 recruiting

  • Queen Mary Hospital

    Pok Fu Lam, Hong Kong Island

    Recruiting

Other trials in Hong Kong

About this study

Official title: 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, 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.

Read the detailed description

This study will evaluate the safety and efficacy of zipalertinib in participants with locally advanced or metastatic NSCLC harboring EGFR ex20ins mutations or other uncommon/single or compound Epidermal Growth Factor Receptor Proteins Mutations (EGFRmts). The drug-drug interaction (DDI) substudy will assess the potential DDI effects of zipalertinib on the pharmacokinetics (PK) of cytochrome P450 (CYP) enzyme substrates and transporter substrates and also evaluate the relationship between zipalertinib concentration and QT interval change from baseline. Additionally, dose optimization substudy will be conducted to confirm an optimized dose of zipalertinib monotherapy.

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

  • Cohort A ("prior ex20ins treatment") will include participants harboring EGFR ex20ins who have progressed on or after initial treatment with standard platinum-based chemotherapy and prior treatment with an ex20ins agent for their advanced disease (administered together or separately).
  • Cohort B ("first-line") will include participants harboring EGFR ex20ins who have not received prior treatment for advanced or metastatic disease and are not appropriate candidates for first-line doublet platinum-based chemotherapy or have refused first-line doublet platinum-based chemotherapy.
  • Cohort C ("active brain mets") will include participants harboring EGFR ex20ins or other uncommon single or compound EGFRmts and active brain metastases and/or leptomeningeal disease (LMD). Participants may or may not have had prior treatment for advanced disease.
  • Cohort D ("other uncommon EGFRmts") will include participants harboring other non-ex20ins, excluding C797S (uncommon single or compound) EGFRmts who have not received prior systemic therapy for their locally advanced or metastatic NSCLC disease.

For DDI substudy, participants will be enrolled in two groups:

  • CYP Cocktail Group will receive a single dose of cocktail 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.
  • Transporter Cocktail Group 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.

For dose-optimization substudy, participants with locally advanced or metastatic NSCLC harboring epidermal growth factor receptor protein ex20ins mutations (EGFRmts) will be randomized to receive zipalertinib at different doses with continuous daily dosing until any discontinuation criterion is met. Participants will be enrolled into two groups: Arm A and Arm B, in which they will receive different doses of zipalertinib.

Being tested
TAS6417, CYP Cocktail, Transporter Cocktail
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
Medical subject headings
Carcinoma, Lung Diseases

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • TAS6417Drug

    Also called CLN-081, zipalertinib

    Oral tablets

  • CYP CocktailDrug

    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.

  • Transporter CocktailDrug

    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.

Study groups in NCT05967689
Study groupRoleWhat they receive
Cohort A ("prior ex20ins treatment")ExperimentalCohort 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.
Receives: Drug: TAS6417
Cohort B ("first-line treatment")ExperimentalCohort B participants will receive zipalertinib orally, BID continuously until documentation of PD or until other withdrawal criteria are met, whichever comes first.
Receives: Drug: TAS6417
Cohort C ("active brain mets")ExperimentalCohort C participants will receive zipalertinib orally, BID continuously until documentation of PD or until other withdrawal criteria are met, whichever comes first.
Receives: Drug: TAS6417
Cohort D ("other uncommon EGFRmts").ExperimentalCohort D participants will receive zipalertinib orally, BID continuously until documentation of PD or until other withdrawal criteria are met, whichever comes first.
Receives: Drug: TAS6417
DDI Substudy: CYP Cocktail GroupExperimentalParticipants 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.
Receives: Drug: TAS6417; Drug: CYP Cocktail
DDI Substudy: Transporter Cocktail GroupExperimentalParticipants 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.
Receives: Drug: TAS6417; Drug: Transporter Cocktail
Dose Optimization Substudy: Arm AExperimentalParticipants 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.
Receives: Drug: TAS6417
Dose Optimization Substudy: Arm BExperimentalParticipants 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.
Receives: Drug: TAS6417

What is being measured

The primary outcome is the main question the study is designed to answer.

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

    Measured: Up to approximately 2 years

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

    Measured: Up to approximately 2 years

Secondary outcomes (29)

  1. 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)

    Measured: Up to approximately 2 years

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

    Measured: Up to approximately 2 years

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

    Measured: Up to approximately 2 years

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

    Measured: Up to approximately 2 years

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

    Measured: Up to approximately 2 years

  6. Cohorts 1-4: Disease Control Rate (DCR)

    Measured: Up to approximately 2 years

  7. Cohorts 1-4: Duration of Response (DoR)

    Measured: Up to approximately 2 years

  8. Cohorts 1-4: Progression-free Survival (PFS)

    Measured: Up to approximately 2 years

  9. Cohorts 1-4: Overall Survival (OS)

    Measured: Up to approximately 2 years

  10. Cohort C: Intracranial (i) Overall Response Rate (iORR)

    Measured: Up to approximately 2 years

  11. Cohort C: Intracranial Duration of Complete Response (iDCR)

    Measured: Up to approximately 2 years

  12. Cohort C: Intracranial Duration of Response (iDoR)

    Measured: Up to approximately 2 years

  13. Cohorts 1-4: Minimum Plasma Concentration (Cmin) of Zipalertinib

    Measured: Up to approximately 2 years

  14. DDI Substudy: Change From Baseline in QT interval Corrected for Heart Rate using Fridericia's formula (QTcF) Interval Following Zipalertinib Administration in CYP Cocktail Group

    Measured: Cycle 1 (cycle length = 21 days)

  15. DDI Substudy: Geometric Mean Maximum Plasma Concentration (Cmax) After Multiple Dose Administration of Zipalertinib in CYP Group and Transporter Cocktail Groups

    Measured: Cycle 1 (cycle length = 21 days)

  16. DDI Substudy: Geometric Mean Area Under Curve (AUC) After Multiple Dose Administration of Zipalertinib in CYP Group and Transporter Cocktail Groups

    Measured: Cycle 1 (cycle length = 21 days)

  17. DDI Substudy: Number of Participants with Treatment-Emergent Adverse Events (TEAEs) in CYP Group and Transporter Cocktail

    Measured: Cycle 1 (cycle length = 21 days)

  18. Dose Optimization Substudy: Duration of Response (DoR) as Assessed by BICR and Investigator

    Measured: Up to approximately 2 years

  19. Dose Optimization Substudy: Time to Response as Assessed by BICR and Investigator

    Measured: Up to approximately 2 years

  20. Dose Optimization Substudy: Percent Change in Tumor Size From Baseline as Assessed by BICR and Investigator

    Measured: Up to approximately 2 years

  21. Dose Optimization Substudy: DCR as Assessed by BICR and Investigator

    Measured: Up to approximately 2 years

  22. Dose Optimization Substudy: PFS as Assessed by BICR and Investigator

    Measured: Up to approximately 2 years

  23. Dose Optimization Substudy: 6 Month PFS Rate

    Measured: Up to approximately 2 years

  24. Dose Optimization Substudy: ORR as Assessed by Investigator

    Measured: Up to approximately 2 years

  25. Dose Optimization Substudy: Overall Survival (OS)

    Measured: Up to approximately 2 years

  26. Dose Optimization Substudy: Intracranial ORR (iORR) per Response Assessment in Neuro-oncology Brain Metastases (RANO-BM) Criteria

    Measured: Up to approximately 2 years

  27. Dose Optimization Substudy: Intracranial Duration of Response (iDOR)

    Measured: Up to approximately 2 years

  28. Dose Optimization Substudy: Intracranial Disease Control Rate (iDCR)

    Measured: Up to approximately 2 years

  29. Dose Optimization Substudy: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

    Measured: Up to approximately 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted1 Aug 2023
  2. Study start31 Jul 2023
  3. Primary completion31 Aug 2028 (estimated)
  4. Study completion31 Dec 2028 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
6 Cohorts based on eligibility criteria
Masking
None (open label)
Enrolment
220 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05967689
Sponsor's protocol ID
TAS6417-201
Other IDs
2023-503865-48, 2023
Acronym
REZILIENT2
Status last verified
Oct 2026
First submitted
11 Jul 2023
Last updated
6 Oct 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing TAS6417, CYP Cocktail and Transporter Cocktail in people with Advanced or Metastatic NSCLC Harboring Epidermal Growth Factor Receptor (EGFR) Exon 20 Insertion (ex20ins) Mutations, run by Taiho Oncology, Inc. at 80 sites in 12 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 55 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 6 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 80 sites in United States, Japan, South Korea, France, Spain and 7 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Taiho Oncology, INC (+1 844-878-2446, medicalinformation@taihooncology.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Cohorts 1-4: Objective Response Rate (ORR) (time frame: Up to approximately 2 years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05967689.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Oct 2026.

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