Actively Recruiting

Phase 2
Age: 18Years +
All Genders
NCT05967689

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.

Led by Taiho Oncology, Inc. · Updated on 2026-04-03

220

Participants Needed

80

Research Sites

282 weeks

Total Duration

On this page

AI-Summary

What this Trial Is About

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

Official Title

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.

Who Can Participate

Age: 18Years +
All Genders

Eligibility Criteria

Eligible

You may qualify if you...

  • Provide written informed consent.
  • Be 18 years or older (or meet legal adult age in your country).
  • Have pathologically confirmed locally advanced or metastatic NSCLC with EGFR exon 20 insertion or other uncommon EGFR mutations confirmed by certified local testing.
  • For Cohort A: Have progressed after prior systemic therapy including ex20ins-targeted agents and chemotherapy; stable brain metastases if present.
  • For Cohort B: No prior treatment for advanced disease and not suitable or refused first-line doublet platinum-based chemotherapy; stable brain metastases if present.
  • For Cohort C: Have active brain metastases or leptomeningeal disease measurable by standard criteria; may have had prior treatment.
  • For Cohort D: Have other uncommon EGFR mutations excluding C797S; no prior systemic therapy for advanced disease; stable brain metastases if present.
  • Have measurable disease per RECIST 1.1.
  • Have archival tumor tissue available for mutation status evaluation.
  • Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1.
  • Adequate organ function as defined by laboratory tests.
  • Women of childbearing potential must have a negative pregnancy test before treatment.
  • Both males and females of reproductive potential must agree to use effective contraception during and for one month after treatment.
  • For DDI substudy: Confirmed advanced NSCLC with specified EGFR mutations and prior systemic therapy unless no approved therapy or intolerant/refused.
  • For dose optimization substudy: Confirmed EGFR exon 20 insertion NSCLC with progression after platinum-based chemotherapy; measurable CNS lesions stable or asymptomatic; ECOG PS 0 or 1; adequate organ function.
Not Eligible

You will not qualify if you...

  • Currently receiving an investigational drug or participating in incompatible medical research.
  • Prior treatment with zipalertinib (TAS6417/CLN081).
  • Recent CNS radiotherapy (within 12 weeks), thoracic radiotherapy (within 28 days), or other palliative radiation (within 14 days).
  • Recent anticancer immunotherapy or major surgery within 28 days before first dose.
  • Prior treatment with any EGFR exon 20 insertion-targeted tyrosine kinase inhibitor.
  • Presence of leptomeningeal CNS disease.
  • Unresolved toxicity grade 2 or higher from previous cancer treatment except alopecia or skin pigmentation.
  • History of interstitial lung disease, treatment-related pneumonitis, or active interstitial lung disease.
  • Significant cardiac disease including advanced congestive heart failure, serious arrhythmias, or prolonged QT interval over 470 msec.
  • Unable to swallow tablets or conditions affecting drug absorption.
  • History of another primary malignancy within 2 years unless adequately treated and stable.
  • Uncontrolled hepatitis B, hepatitis C, or HIV infection.
  • COVID-19 infection within 4 weeks prior to enrollment or persistent pulmonary symptoms.
  • Active bleeding disorders.
  • Known allergy to zipalertinib or similar drugs.
  • Pregnant, breastfeeding, or planning pregnancy.
  • Unable or unwilling to comply with study procedures.

AI-Screening

AI-Powered Screening

Complete this quick 3-step screening to check your eligibility

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Trial Site Locations

Total: 80 locations

1

University of Alabama at Birmingham

Birmingham, Alabama, United States, 35294

Withdrawn

2

City of Hope - Duarte

Duarte, California, United States, 91010

Actively Recruiting

3

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States, 02215

Actively Recruiting

4

Comprehensive Cancer Centers of Nevada - Central Valley - Twain

Las Vegas, Nevada, United States, 89169

Actively Recruiting

5

Memorial Sloan Kettering Cancer Center - Basking Ridge

Basking Ridge, New Jersey, United States, 07920

Actively Recruiting

6

Memorial Sloan Kettering Cancer Center - Monmouth

Middletown, New Jersey, United States, 07748

Actively Recruiting

7

Memorial Sloan Kettering Cancer Center - Bergen

Montvale, New Jersey, United States, 07645

Actively Recruiting

8

Memorial Sloan Kettering Cancer Center - Commack

Commack, New York, United States, 11725

Actively Recruiting

9

Memorial Sloan Kettering Cancer Center - Westchester

Harrison, New York, United States, 10604

Actively Recruiting

10

MSK Cancer Center

Long Island City, New York, United States, 11101

Actively Recruiting

11

Memorial Sloan Kettering Cancer Center - Nassau

Uniondale, New York, United States, 11553

Actively Recruiting

12

Gabrail Cancer and Research Center

Canton, Ohio, United States, 44718

Active, Not Recruiting

13

Zangmeister Cancer Center

Columbus, Ohio, United States, 43219

Withdrawn

14

The Toledo Clinic Cancer Center

Toledo, Ohio, United States, 43623

Withdrawn

15

SCRI Oncology Partners

Nashville, Tennessee, United States, 37203

Actively Recruiting

16

University of Texas MD Anderson Cancer Center

Houston, Texas, United States, 77030

Actively Recruiting

17

Virginia Cancer Specialists

Fairfax, Virginia, United States, 22031

Actively Recruiting

18

IDS Pharmacy

Milwaukee, Wisconsin, United States, 53226

Actively Recruiting

19

Bankstown-Lidcombe Hospital

Bankstown, New South Wales, Australia, 2200

Actively Recruiting

20

Genesis Care North Shore

Saint Leonards, New South Wales, Australia, 2065

Actively Recruiting

21

Joondalup Hospital Pharmacy

Joondalup, Western Australia, Australia, 6027

Actively Recruiting

22

William Osler Health System - Brampton Civic Hospital

Brampton, Canada, L6R 3J7

Actively Recruiting

23

Nouvel Hôpital Civil

Strasbourg, Aslace, France, 67091

Actively Recruiting

24

Centre Leon Berard

Lyon, Auvergne-Rhône-Alpes, France, 69008

Actively Recruiting

25

CHU Caen Normandie

Caen, Basse-Normandie, France, 14033

Actively Recruiting

26

Centre Hospitalier Universitaire Limoges

Limoges, Limousin, France, 87042

Actively Recruiting

27

Hopital Haut Leveque

Pessac, New Aquitaine, France, 33604

Actively Recruiting

28

Hôpital Nord de Marseille

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

Actively Recruiting

29

Hopital Nord Laennec

Saint-Herblain, France, 44800

Actively Recruiting

30

Hopital Ambroise Pare

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

Actively Recruiting

31

Institut Curie

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

Actively Recruiting

32

Gesundheit Nordhessen Holding AG

Kassel, Hassen, Germany, 34125

Actively Recruiting

33

Uniklinik Dresden

Dresden, Germany, 01307

Actively Recruiting

34

UKGM Studienzentrale

Giessen, Germany, 35392

Actively Recruiting

35

UKR Innere Med II Pneumologie

Regensburg, Germany, 93053

Withdrawn

36

Queen Mary Hospital

Pok Fu Lam, Hong Kong Island, Hong Kong

Active, Not Recruiting

37

Azienda Ospedaliero - Universitaria Careggi

Florence, Florence, Italy, 50134

Actively Recruiting

38

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

Meldola, Forli-Cesena, Italy, 47014

Actively Recruiting

39

Azienda Socio-Sanitaria Territoriale di Cremona

Cremona, Italy, 26100

Actively Recruiting

40

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

Milan, Italy, 20132

Actively Recruiting

41

Azienda Ospedaliero-Universitaria di Parma

Parma, Italy, 43126

Actively Recruiting

42

Ospedale S. Maria delle Croci

Ravenna, Italy, 48121

Actively Recruiting

43

Aichi Cancer Center

Nagoya, Aichi-ken, Japan, 464-8681

Actively Recruiting

44

National Cancer Center Hospital East

Kashiwa-shi, Chiba, Japan, 277-8577

Actively Recruiting

45

NHO Kyushu Cancer Center

Fukuoka, Hukuoka, Japan, 811-1395

Actively Recruiting

46

Sendai Kousei Hospital

Sendai, Miyagi, Japan, 980-0873

Actively Recruiting

47

Niigata Cancer Center Hospital

Niigata, Niigata, Japan, 951-8566

Actively Recruiting

48

Kindai University Hospital

Sayama, Osaka, Japan, 589-8511

Actively Recruiting

49

Shizuoka Cancer Center

Sunto-gun, Shizuoka, Japan, 411-8777

Actively Recruiting

50

National Cancer Center Hospital

Chuo Ku, Tokyo, Japan, 104-0045

Actively Recruiting

51

Cancer Institute Hospital of JFCR

Koto-ku, Tokyo, Japan, 135-8550

Actively Recruiting

52

Okayama University Hospital

Okayama, Japan, 700-8558

Actively Recruiting

53

National Cancer Center - Korea

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

Withdrawn

54

Saint Vincent's Hospital

Suwon, Gyeonggi-do, South Korea, 16247

Actively Recruiting

55

Ajou University Hospital

Suwon, Gyeonggi-do, South Korea, 16499

Actively Recruiting

56

Gyeongsang National University Hospital

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

Actively Recruiting

57

Inha University Hospital

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

Actively Recruiting

58

Chonnam National University Hwasun Hospital

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

Actively Recruiting

59

Seoul National University Hospital

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

Active, Not Recruiting

60

Asan Medical Center

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

Actively Recruiting

61

Korea University Guro Hospital

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

Actively Recruiting

62

Seoul St. Mary's Hospital

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

Withdrawn

63

Hospital Regional Universitario de Málaga - Hospital General

Málaga, Malaga, Spain, 29010

Actively Recruiting

64

UOMi Clinica Mi Tres Torres

Barcelona, Spain, 08017

Actively Recruiting

65

Hospital Quirónsalud Barcelona

Barcelona, Spain, 08023

Actively Recruiting

66

Hospital Clinic de Barcelona

Barcelona, Spain, 08036

Actively Recruiting

67

Complejo Hospitalario de Jaen

Jaén, Spain, 23007

Actively Recruiting

68

MD Anderson Cancer Center Madrid

Madrid, Spain, 28033

Actively Recruiting

69

Hospital Universitario Fundación Jiménez Díaz

Madrid, Spain, 28040

Actively Recruiting

70

Hospital Universitario 12 de Octubre

Madrid, Spain, 28041

Actively Recruiting

71

Hospital La Paz

Madrid, Spain, 28046

Actively Recruiting

72

Istinye Üniversite Hastanesi Liv Hospital Bahcesehir

Esenyurt, Istanbul, Turkey (Türkiye), 34517

Actively Recruiting

73

Medical Park Seyhan Hastanesi

Adana, Turkey (Türkiye), 01140

Actively Recruiting

74

Trakya Üniversitesi Saglik Arastirma ve Uygulama Merkezi

Edirne, Turkey (Türkiye), 22030

Actively Recruiting

75

Bagcilar Medipol Mega Universite Hastanesi

Istanbul, Turkey (Türkiye), 34214

Withdrawn

76

Prof. Dr. Suleyman Yalcin Sehir Hastanesi

Istanbul, Turkey (Türkiye), 34722

Actively Recruiting

77

The Royal Free Hospital NHS Foundation Trust

Barnet, England, United Kingdom, EN5 3DJ

Actively Recruiting

78

Royal Free London NHS Foundation Trust

London, England, United Kingdom, NW3 2QG

Actively Recruiting

79

The Christie NHS Foundation Trust

Manchester, England, United Kingdom, M20 4BX

Actively Recruiting

80

Nottingham University Hospitals NHS Trust

Nottingham, England, United Kingdom, NG5 1PB

Actively Recruiting

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Research Team

T

Taiho Oncology, INC

CONTACT

How is the study designed?

Study Type

INTERVENTIONAL

Masking

NONE

Allocation

RANDOMIZED

Model

PARALLEL

Primary Purpose

TREATMENT

Number of Arms

8

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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. | DecenTrialz