Informations générales (source: ClinicalTrials.gov)
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. (REZILIENT2)
Interventional
Phase 2
Taiho Oncology, Inc. (Voir sur ClinicalTrials)
juillet 2023
août 2026
05 avril 2025
The purpose of this study is to evaluate the safety and efficacy of zipalertinib in
participants with locally advanced or metastatic Non-Small Cell Lung Cancer (NSCLC)
harboring EGFR ex20ins mutations and other mutations.
Etablissements
| Les établissements d'Île-de-France ayant mis à jour leurs données Origine et niveau de fiabilité des données | |||||
|---|---|---|---|---|---|
| CLCC INSTITUT CURIE | 10/04/2025 13:12:08 | Contact (sur clinicalTrials) | |||
| Les établissements d'Île-de-France dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données | |||||
| CLCC INSTITUT GUSTAVE ROUSSY | Contact (sur clinicalTrials) | ||||
| Les établissements sans correspondance certaine dans le répertoire FINESS dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données | |||||
| Centre Hospitalier Universitaire De Nantes - Hôpital Nord Laennec - 44805 - Saint-Herblain - Loire-Atlantique - France | Contact (sur clinicalTrials) | ||||
| Centre Hospitalier Universitaire Limoges - 87042 - Limoges cedex - Limousin - France | Contact (sur clinicalTrials) | ||||
| Centre Léon Bérard - 69008 - Lyon - Rhone-Alpes - France | Contact (sur clinicalTrials) | ||||
| Hôpital Ambroise-Paré - 92100 - Boulogne-Billancourt - Île-de-France - France | Contact (sur clinicalTrials) | ||||
| Hôpital Côte De Nacre - 14033 - Caen cedex 9 - Basse-Normandie - France | Contact (sur clinicalTrials) | ||||
| Hôpital Haut-Lévêque - 33604 - Pessac - Nouvelle-Aquitaine - France | Contact (sur clinicalTrials) | ||||
| Hôpital Nord de Marseille - 13015 - Marseille - Provence Alpes Cote d´Azur - France | Contact (sur clinicalTrials) | ||||
| Les Hôpitaux Universitaires de Strasbourg - 67091 - Strasbourg cedex - Aslace - France | Contact (sur clinicalTrials) | ||||
Critères
Tous
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.
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.
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.