Informations générales (source: ClinicalTrials.gov)
Randomized, Controlled, Open-label, Phase 3, Global Multi - Center Trial to Assess the Efficacy and Safety of Zipalertinib Plus Chemotherapy Versus Chemotherapy Alone, in Patients with Previously Untreated, Locally Advanced or Metastatic Nonsquamous Non-Small Cell Lung Cancer (NSCLC) with Epidermal Growth Factor Receptor (EGFR) Exon 20 Insertion (ex20ins) Mutations (REZILIENT3)
Interventional
Phase 3
Taiho Oncology, Inc. (Voir sur ClinicalTrials)
juin 2023
août 2026
26 septembre 2024
The purpose of this study is to evaluate the safety and efficacy of zipalertinib in
combination with standard first-line platinum-based chemotherapy compared to chemotherapy
alone, in patients with locally advanced or metastatic NSCLC with EGFR ex20ins mutations.
Etablissements
| Les établissements d'Île-de-France ayant mis à jour leurs données Origine et niveau de fiabilité des données | |||||
|---|---|---|---|---|---|
| CLCC INSTITUT CURIE | 04/09/2024 13:49:38 | 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 Le Mans - 72037 - Le Mans cedex 9 - Pays De La Loire - France | Contact (sur clinicalTrials) | ||||
| Centre Hospitalier Universitaire Limoges - 87042 - Limoges - Limousin - 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) | ||||
| Les Hôpitaux Universitaires de Strasbourg - 67091 - Strasbourg cedex - Alsace - France | Contact (sur clinicalTrials) | ||||
Critères
Tous
Inclusion-
1. Provide written informed consent.
2. ≥18 years of age (or meets the country's regulatory definition for legal adult age,
whichever is greater).
3. Pathologically confirmed, locally advanced or metastatic nonsquamous NSCLC
4. Has not received any prior systemic treatment for their locally advanced or
metastatic nonsquamous NSCLC. Prior adjuvant/neoadjuvant treatment received >6
months prior to first dose of study treatment is allowed for early-stage
NSCLC. Prior monotherapy with an approved EGFR TKI (ie, gefitinib, erlotinib,
afatinib, dacomitinib, or osimertinib) as nonstandard first-line therapy for the
treatment of locally advanced or metastatic disease is allowed if all of the
following criteria are met:
1. Treatment duration did not exceed 8 weeks;
2. Lack of disease response was documented (radiographically) by an increase in
tumor burden (a copy of the computerized tomography [CT] report showing
increase in tumor burden from baseline should be submitted);
3. Associated toxicities have resolved to baseline; and
4. The EGFR TKI was discontinued at least 2 weeks or 4 half-lives prior to
randomization, whichever is longer.
Prior therapy with EGFR TKI agents targeting exon20ins mutations including
amivantamab, mobocertinib, sunvozertinib, furmonertinib, and poziotinib is not
allowed.
5. Documented EGFR mutation status, as determined by local testing performed at a CLIA
certified (US) or accredited (outside of the US) local laboratory, defined as
follows:
1. Part A: EGFR ex20ins or other uncommon single or compound EGFR mutation
2. Part B: EGFR ex20ins mutation
6. Archival tumor tissue available for submission, with minimum quantity sufficient to
evaluate EGFR mutation status and, where possible, other biomarkers. Patients with
insufficient tissue (details provided in laboratory manual) may be eligible
following discussion with the sponsor; a fresh biopsy will not be required.
7. Patients with brain metastasis(es) who have previously received definitive local
treatment and have stable central nervous system (CNS) disease (defined as being
neurologically stable and off corticosteroid for at least 2 weeks prior to
enrollment) are eligible. If brain metastases are diagnosed on screening imaging,
the patient may be rescreened for eligibility after definitive treatment.
b. Asymptomatic brain metastases ≤2 cm in size can be eligible for inclusion if, in
the opinion of the Investigator, immediate definitive treatment is not indicated.
8. At least one measurable lesion as determined per RECIST 1.1 for patients enrolling
to Part B. Patients enrolling to Part A may be enrolled without measurable disease.
9. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
10. Adequate organ function, as defined by the laboratory value
11. Have a life expectancy of at least 3 months as assessed by the investigator.
12. 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 postmenopausal (no menses
for 12 months without an alternative medical cause) or permanently sterile
(hysterectomy, bilateral salpingectomy, or bilateral oophorectomy).
13. Both males and females of reproductive potential must agree to use effective birth
control during the study prior to the first dose and for 6 months after the last
dose of study treatment or longer, based on local requirements.
Exclusion -
1. Is currently receiving an investigational drug in a clinical trial or participating
in any other type of medical research judged not to be scientifically or medically
compatible with this study.
2. Prior treatment with any of the following within the specific time frame specified:
1. Zipalertinib (TAS6417/CLN-081) at any time.
2. Thoracic radiotherapy ≤28 days, palliative radiation of nonthoracic disease ≤14
days, or palliative radiation of a single lesion ≤7 days prior to first dose of
study treatment.
3. Major surgery (excluding placement of vascular access) ≤28 days prior to first
dose of study treatment.
4. 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.
3. Have any unresolved toxicity of Grade ≥2 from previous anticancer treatment in the
neoadjuvant or adjuvant setting, 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 any 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 calculated using Fridericia's
formula (QTcF).
6. Unable to swallow tablets or has any disease or condition that may significantly
affect gastrointestinal (GI) absorption of zipalertinib (such as inflammatory bowel
disease, malabsorption syndrome, or prior GI 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. Previously treated malignancy, if all treatment for that malignancy was
completed at least 2 years prior to first dose of study treatment, and no
current evidence of disease
4. Concurrent malignancy determined to be clinically stable and not requiring
tumor directed treatment
8. Known history of hepatitis B, hepatitis C, or human immunodeficiency virus (HIV)
that is unstable or not controlled with treatment.
9. History of COVID-19 infection within 4 weeks prior to enrolment and/or have
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. To platinum-containing drugs (ie, cisplatin, carboplatin),
pemetrexed, or any known excipients of these drugs. b. Contraindications toning
drugs (ie, cisplatin, carboplatin) or pemetrexed according to the respective local
labels.
12. History of leptomeningeal disease and spinal cord compression.
13. Is unable or unwilling to take dexamethasone, folic acid, and/or vitamin B12
supplementation during treatment with pemetrexed.
14. Is pregnant or lactating or planning to become pregnant
15. The patient is, in the investigator's opinion, unable or unwilling to comply with
the trial procedures.
1. Provide written informed consent.
2. ≥18 years of age (or meets the country's regulatory definition for legal adult age,
whichever is greater).
3. Pathologically confirmed, locally advanced or metastatic nonsquamous NSCLC
4. Has not received any prior systemic treatment for their locally advanced or
metastatic nonsquamous NSCLC. Prior adjuvant/neoadjuvant treatment received >6
months prior to first dose of study treatment is allowed for early-stage
NSCLC. Prior monotherapy with an approved EGFR TKI (ie, gefitinib, erlotinib,
afatinib, dacomitinib, or osimertinib) as nonstandard first-line therapy for the
treatment of locally advanced or metastatic disease is allowed if all of the
following criteria are met:
1. Treatment duration did not exceed 8 weeks;
2. Lack of disease response was documented (radiographically) by an increase in
tumor burden (a copy of the computerized tomography [CT] report showing
increase in tumor burden from baseline should be submitted);
3. Associated toxicities have resolved to baseline; and
4. The EGFR TKI was discontinued at least 2 weeks or 4 half-lives prior to
randomization, whichever is longer.
Prior therapy with EGFR TKI agents targeting exon20ins mutations including
amivantamab, mobocertinib, sunvozertinib, furmonertinib, and poziotinib is not
allowed.
5. Documented EGFR mutation status, as determined by local testing performed at a CLIA
certified (US) or accredited (outside of the US) local laboratory, defined as
follows:
1. Part A: EGFR ex20ins or other uncommon single or compound EGFR mutation
2. Part B: EGFR ex20ins mutation
6. Archival tumor tissue available for submission, with minimum quantity sufficient to
evaluate EGFR mutation status and, where possible, other biomarkers. Patients with
insufficient tissue (details provided in laboratory manual) may be eligible
following discussion with the sponsor; a fresh biopsy will not be required.
7. Patients with brain metastasis(es) who have previously received definitive local
treatment and have stable central nervous system (CNS) disease (defined as being
neurologically stable and off corticosteroid for at least 2 weeks prior to
enrollment) are eligible. If brain metastases are diagnosed on screening imaging,
the patient may be rescreened for eligibility after definitive treatment.
b. Asymptomatic brain metastases ≤2 cm in size can be eligible for inclusion if, in
the opinion of the Investigator, immediate definitive treatment is not indicated.
8. At least one measurable lesion as determined per RECIST 1.1 for patients enrolling
to Part B. Patients enrolling to Part A may be enrolled without measurable disease.
9. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
10. Adequate organ function, as defined by the laboratory value
11. Have a life expectancy of at least 3 months as assessed by the investigator.
12. 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 postmenopausal (no menses
for 12 months without an alternative medical cause) or permanently sterile
(hysterectomy, bilateral salpingectomy, or bilateral oophorectomy).
13. Both males and females of reproductive potential must agree to use effective birth
control during the study prior to the first dose and for 6 months after the last
dose of study treatment or longer, based on local requirements.
Exclusion -
1. Is currently receiving an investigational drug in a clinical trial or participating
in any other type of medical research judged not to be scientifically or medically
compatible with this study.
2. Prior treatment with any of the following within the specific time frame specified:
1. Zipalertinib (TAS6417/CLN-081) at any time.
2. Thoracic radiotherapy ≤28 days, palliative radiation of nonthoracic disease ≤14
days, or palliative radiation of a single lesion ≤7 days prior to first dose of
study treatment.
3. Major surgery (excluding placement of vascular access) ≤28 days prior to first
dose of study treatment.
4. 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.
3. Have any unresolved toxicity of Grade ≥2 from previous anticancer treatment in the
neoadjuvant or adjuvant setting, 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 any 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 calculated using Fridericia's
formula (QTcF).
6. Unable to swallow tablets or has any disease or condition that may significantly
affect gastrointestinal (GI) absorption of zipalertinib (such as inflammatory bowel
disease, malabsorption syndrome, or prior GI 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. Previously treated malignancy, if all treatment for that malignancy was
completed at least 2 years prior to first dose of study treatment, and no
current evidence of disease
4. Concurrent malignancy determined to be clinically stable and not requiring
tumor directed treatment
8. Known history of hepatitis B, hepatitis C, or human immunodeficiency virus (HIV)
that is unstable or not controlled with treatment.
9. History of COVID-19 infection within 4 weeks prior to enrolment and/or have
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. To platinum-containing drugs (ie, cisplatin, carboplatin),
pemetrexed, or any known excipients of these drugs. b. Contraindications toning
drugs (ie, cisplatin, carboplatin) or pemetrexed according to the respective local
labels.
12. History of leptomeningeal disease and spinal cord compression.
13. Is unable or unwilling to take dexamethasone, folic acid, and/or vitamin B12
supplementation during treatment with pemetrexed.
14. Is pregnant or lactating or planning to become pregnant
15. The patient is, in the investigator's opinion, unable or unwilling to comply with
the trial procedures.