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
octobre 2025
28 décembre 2024
The purpose of this study is to evaluate the safety and efficacy of zipalertinib in
patients with locally advanced or metastatic 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 | 04/12/2024 12:44:13 | 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 patients:
- Documented EGFR ex20ins mutation 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 with an agent targeting ex20ins, either
alone or in combination with standard platinum-based chemotherapy for the
treatment of advanced disease. Patients who discontinued previous treatment due
to unacceptable toxicity are eligible.
- Patients with brain metastasis must be neurologically stable. Patients 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. Patients with history of uncontrolled seizures or
leptomeningeal disease are not eligible.
Cohort B patients:
- Documented EGFR ex20ins mutation status, as determined by local testing
performed at a CLIA certified (US) or locally certified laboratory (outside the
US).
- Not received prior systemic therapy for locally advanced or metastatic disease.
Prior adjuvant/neoadjuvant treatment for early-stage disease must have been
completed >6 months prior to the first dose of study treatment.
- Patients with brain metastasis must be neurologically stable. Patients 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. Patients with history of uncontrolled seizures or
leptomeningeal disease are not eligible.
Cohort C patients:
- Documented EGFR ex20ins mutation status, as determined by local testing
performed at a CLIA certified (US) or locally certified laboratory (outside the
US).
- Presence of brain metastasis(es), which may be measurable or nonmeasurable by
RANO-BM criteria, characterized as one of the following:
- Newly diagnosed and/or progressive brain metastasis (es) not subjected to
CNS-directed therapy, OR
- Leptomeningeal disease (LMD) confirmed by a positive cerebrospinal fluid
cytology, or unequivocal radiographic and/or clinical determination.
Cohort D patients:
- Documented other non-ex20ins uncommon single or compound EGFRmt status, 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 manual.
- Patients with brain metastasis must be neurologically stable. Patients 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. Patients with history of uncontrolled seizures or
leptomeningeal disease are not eligible.
4. Measurable disease per 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). Patients with insufficient tissue may be eligible following
discussion with the sponsor.
6. Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0 or 17. Adequate
organ function, as defined by the hematologic, renal and hepatic laboratory values
4. Women of childbearing potential (WOCBP) must have a negative serum pregnancy test
prior to administration of the first dose of study treatment. Female patients 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).
5. 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 6 months
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 patients:
- Documented EGFR ex20ins mutation 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 with an agent targeting ex20ins, either
alone or in combination with standard platinum-based chemotherapy for the
treatment of advanced disease. Patients who discontinued previous treatment due
to unacceptable toxicity are eligible.
- Patients with brain metastasis must be neurologically stable. Patients 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. Patients with history of uncontrolled seizures or
leptomeningeal disease are not eligible.
Cohort B patients:
- Documented EGFR ex20ins mutation status, as determined by local testing
performed at a CLIA certified (US) or locally certified laboratory (outside the
US).
- Not received prior systemic therapy for locally advanced or metastatic disease.
Prior adjuvant/neoadjuvant treatment for early-stage disease must have been
completed >6 months prior to the first dose of study treatment.
- Patients with brain metastasis must be neurologically stable. Patients 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. Patients with history of uncontrolled seizures or
leptomeningeal disease are not eligible.
Cohort C patients:
- Documented EGFR ex20ins mutation status, as determined by local testing
performed at a CLIA certified (US) or locally certified laboratory (outside the
US).
- Presence of brain metastasis(es), which may be measurable or nonmeasurable by
RANO-BM criteria, characterized as one of the following:
- Newly diagnosed and/or progressive brain metastasis (es) not subjected to
CNS-directed therapy, OR
- Leptomeningeal disease (LMD) confirmed by a positive cerebrospinal fluid
cytology, or unequivocal radiographic and/or clinical determination.
Cohort D patients:
- Documented other non-ex20ins uncommon single or compound EGFRmt status, 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 manual.
- Patients with brain metastasis must be neurologically stable. Patients 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. Patients with history of uncontrolled seizures or
leptomeningeal disease are not eligible.
4. Measurable disease per 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). Patients with insufficient tissue may be eligible following
discussion with the sponsor.
6. Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0 or 17. Adequate
organ function, as defined by the hematologic, renal and hepatic laboratory values
4. Women of childbearing potential (WOCBP) must have a negative serum pregnancy test
prior to administration of the first dose of study treatment. Female patients 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).
5. 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 6 months
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 ≤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.
3. Have any unresolved toxicity of Grade ≥2 from previous anticancer treatment, except
for Grade 2 alopecia or skin pigmentation. Patients 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 (Appendix A)
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/capsules 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. Patients 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. Patients 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 COVID-19 infection within 4 weeks prior to enrolment 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 or lactating.