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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05967689




Registration number
NCT05967689
Ethics application status
Date submitted
11/07/2023
Date registered
1/08/2023

Titles & IDs
Public 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.
Scientific 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.
Secondary ID [1] 0 0
2023-503865-48
Secondary ID [2] 0 0
TAS6417-201
Universal Trial Number (UTN)
Trial acronym
REZILIENT2
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Advanced or Metastatic NSCLC Harboring Epidermal Growth Factor Receptor (EGFR) Exon 20 Insertion (ex20ins) Mutations 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lung - Non small cell

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - TAS6417

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

Experimental: Cohort B ("first-line treatment") - Cohort B participants will receive zipalertinib orally twice a day (BID) continuously until documentation of PD or until other withdrawal criteria are met, whichever comes first.

Experimental: Cohort C ("active brain mets") - Cohort C participants will receive zipalertinib orally twice a day (BID) continuously until documentation of PD or until other withdrawal criteria are met, whichever comes first.

Experimental: Cohort D ("other uncommon EGFRmts"). - Cohort D participants will receive zipalertinib orally twice a day (BID) continuously until documentation of PD or until other withdrawal criteria are met, whichever comes first.


Treatment: Drugs: TAS6417
Oral tablets
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
All Cohorts: Objective Response Rate (ORR)
Timepoint [1] 0 0
Up to approximately 2 years
Secondary outcome [1] 0 0
All Cohorts: 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)
Timepoint [1] 0 0
Up to approximately 2 years
Secondary outcome [2] 0 0
All Cohorts: Number of Participants with Clinically Significant Changes in Clinical Laboratory Parameters
Timepoint [2] 0 0
Up to approximately 2 years
Secondary outcome [3] 0 0
All Cohorts: Number of Participants with Clinically Significant Changes in Vital Signs
Timepoint [3] 0 0
Up to approximately 2 years
Secondary outcome [4] 0 0
All Cohorts: Number of Participants with Clinically Significant Changes in Electrocardiogram (ECG) Parameters
Timepoint [4] 0 0
Up to approximately 2 years
Secondary outcome [5] 0 0
All Cohorts: Number of participants With Change in Left Ventricular Ejection Fraction (LVEF) Evaluated Using Electrocardiography (ECHO) and Multigated Acquisition (MUGA) Scan
Timepoint [5] 0 0
Up to approximately 2 years
Secondary outcome [6] 0 0
All Cohorts: Disease control rate (DCR)
Timepoint [6] 0 0
Up to approximately 2 years
Secondary outcome [7] 0 0
All Cohorts: Duration of response (DoR)
Timepoint [7] 0 0
Up to approximately 2 years
Secondary outcome [8] 0 0
All Cohorts: Progression-free survival (PFS)
Timepoint [8] 0 0
Up to approximately 2 years
Secondary outcome [9] 0 0
All Cohorts: Overall Survival (OS)
Timepoint [9] 0 0
Up to approximately 2 years
Secondary outcome [10] 0 0
Cohort C: Intracranial (i) Overall Response Rate (iORR)
Timepoint [10] 0 0
Up to approximately 2 years
Secondary outcome [11] 0 0
Cohort C: Intracranial Duration of Complete Response (iDCR)
Timepoint [11] 0 0
Up to approximately 2 years
Secondary outcome [12] 0 0
Cohort C: Intracranial Duration of Response (iDoR)
Timepoint [12] 0 0
Up to approximately 2 years
Secondary outcome [13] 0 0
All Cohorts: Minimum Plasma Concentration (Cmin) of Zipalertinib
Timepoint [13] 0 0
Up to approximately 2 years

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Patient 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. Patient has received Zipalertinib (TAS6417/CLN081) at any time
2. Thoracic radiotherapy =28 days or palliative radiation (gamma knife radiotherapy is allowed) =14 days prior to the first dose of study treatment
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. 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 of study treatment
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 of the breast or cervix in situ
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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
27/07/2023
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
31/08/2026
Actual
Sample size
Target
160
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,WA
Recruitment hospital [1] 0 0
Bankstown-Lidcombe Hospital - Bankstown
Recruitment hospital [2] 0 0
Genesis Care North Shore - Saint Leonards
Recruitment hospital [3] 0 0
Joondalup Hospital Pharmacy - Joondalup
Recruitment postcode(s) [1] 0 0
2200 - Bankstown
Recruitment postcode(s) [2] 0 0
2065 - Saint Leonards
Recruitment postcode(s) [3] 0 0
6027 - Joondalup
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Massachusetts
Country [4] 0 0
United States of America
State/province [4] 0 0
Nevada
Country [5] 0 0
United States of America
State/province [5] 0 0
New Jersey
Country [6] 0 0
United States of America
State/province [6] 0 0
New York
Country [7] 0 0
United States of America
State/province [7] 0 0
Ohio
Country [8] 0 0
United States of America
State/province [8] 0 0
Tennessee
Country [9] 0 0
United States of America
State/province [9] 0 0
Texas
Country [10] 0 0
United States of America
State/province [10] 0 0
Virginia
Country [11] 0 0
United States of America
State/province [11] 0 0
Wisconsin
Country [12] 0 0
Canada
State/province [12] 0 0
Quebec
Country [13] 0 0
Canada
State/province [13] 0 0
Brampton
Country [14] 0 0
France
State/province [14] 0 0
Aslace
Country [15] 0 0
France
State/province [15] 0 0
Basse-Normandie
Country [16] 0 0
France
State/province [16] 0 0
Ile-de-France
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France
State/province [17] 0 0
Limousin
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France
State/province [18] 0 0
Nouvelle-Aquitaine
Country [19] 0 0
France
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Provence Alpes Cote d´Azur
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France
State/province [20] 0 0
Rhone-Alpes
Country [21] 0 0
France
State/province [21] 0 0
Avignon
Country [22] 0 0
France
State/province [22] 0 0
Saint-Herblain
Country [23] 0 0
France
State/province [23] 0 0
Île-de-France
Country [24] 0 0
Germany
State/province [24] 0 0
Baden-Wuerttemberg
Country [25] 0 0
Germany
State/province [25] 0 0
Hassen
Country [26] 0 0
Germany
State/province [26] 0 0
Dresden
Country [27] 0 0
Germany
State/province [27] 0 0
Gießen
Country [28] 0 0
Germany
State/province [28] 0 0
Hamburg
Country [29] 0 0
Germany
State/province [29] 0 0
München
Country [30] 0 0
Germany
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Regensburg
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Hong Kong
State/province [31] 0 0
Hong Kong Island
Country [32] 0 0
Hong Kong
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Sha Tin
Country [33] 0 0
Italy
State/province [33] 0 0
Florence
Country [34] 0 0
Italy
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Forli-Cesena
Country [35] 0 0
Italy
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Alessandria
Country [36] 0 0
Italy
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Bologna
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Italy
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Catania
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Italy
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Cremona
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Italy
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Genova
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Italy
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Milan
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Italy
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Modena
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Italy
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Parma
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Italy
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Piacenza
Country [44] 0 0
Italy
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Ravenna
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Italy
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Roma
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Japan
State/province [46] 0 0
Aichi
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Japan
State/province [47] 0 0
Chiba
Country [48] 0 0
Japan
State/province [48] 0 0
Hukuoka
Country [49] 0 0
Japan
State/province [49] 0 0
Miyagi
Country [50] 0 0
Japan
State/province [50] 0 0
Niigata
Country [51] 0 0
Japan
State/province [51] 0 0
Osaka
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Japan
State/province [52] 0 0
Sizuoka
Country [53] 0 0
Japan
State/province [53] 0 0
Tokyo
Country [54] 0 0
Japan
State/province [54] 0 0
Okayama
Country [55] 0 0
Korea, Republic of
State/province [55] 0 0
Gyeonggi-Do
Country [56] 0 0
Korea, Republic of
State/province [56] 0 0
Gyeonggi-do
Country [57] 0 0
Korea, Republic of
State/province [57] 0 0
Gyeongsangnamdo [Kyongsangnam-do]
Country [58] 0 0
Korea, Republic of
State/province [58] 0 0
Incheon Gwang'yeogsi [Inch'on-Kwangyokshi]
Country [59] 0 0
Korea, Republic of
State/province [59] 0 0
Jeollanam-do
Country [60] 0 0
Korea, Republic of
State/province [60] 0 0
Seoul Teugbyeolsi [Seoul-T'ukpyolshi]
Country [61] 0 0
Spain
State/province [61] 0 0
Malaga
Country [62] 0 0
Spain
State/province [62] 0 0
Barcelona
Country [63] 0 0
Spain
State/province [63] 0 0
Jaén
Country [64] 0 0
Spain
State/province [64] 0 0
Madrid
Country [65] 0 0
Turkey
State/province [65] 0 0
Ankara
Country [66] 0 0
Turkey
State/province [66] 0 0
Istanbul
Country [67] 0 0
Turkey
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Adana
Country [68] 0 0
Turkey
State/province [68] 0 0
Edirne
Country [69] 0 0
United Kingdom
State/province [69] 0 0
England

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Taiho Oncology, Inc.
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Taiho Oncology, INC
Address 0 0
Country 0 0
Phone 0 0
+1 844-878-2446
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries

Data sharing statement


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT05967689