Informations générales (source: ClinicalTrials.gov)
A Phase II Study of the BRAF Inhibitor Encorafenib in Combination with the MEK Inhibitor Binimetinib in Patients with BRAFV600E-mutant Metastatic Non-small Cell Lung Cancer (ENCO-BRAF)
Interventional
Phase 2
Intergroupe Francophone de Cancerologie Thoracique (Voir sur ClinicalTrials)
janvier 2021
mars 2026
17 octobre 2024
A Phase II study of the BRAF inhibitor Encorafenib in combination with the MEK inhibitor
Binimetinib in Patients with BRAFV600E-mutant metastatic Non-small Cell Lung Cancer
Etablissements
| Les établissements d'Île-de-France ayant mis à jour leurs données Origine et niveau de fiabilité des données | |||||
|---|---|---|---|---|---|
| CHI DE CRETEIL | Jean Bernard AULIAC | 29/03/2024 01:29:31 | Contacter | ||
| CLCC INSTITUT CURIE | 04/09/2024 13:49:42 | Contacter | |||
| CLCC INSTITUT GUSTAVE ROUSSY | David PLANCHARD | 10/04/2024 12:53:50 | Contacter | ||
| HOPITAL FOCH | ANNE CECILE METIVIER | 21/10/2024 07:07:18 | Contacter | ||
| Les établissements d'Île-de-France dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données | |||||
| AP-HP - Hôpital Bichat | Gérard ZALCMAN, Pr | Contact (sur clinicalTrials) | |||
| AP-HP - Hôpital Cochin | Marie Wislez, Pr | Contact (sur clinicalTrials) | |||
| IFSI AP-HP DE L'HÔPITAL TENON | Vincent Fallet, Dr | Contact (sur clinicalTrials) | |||
| Les établissements hors Île-de-France dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données | |||||
| Brest - CHU - Brest - France | Margaux GEIER, Dr | Contact (sur clinicalTrials) | |||
| Centre Georges François Leclerc - Dijon - France | Aurélie LAGRANGE | Contact (sur clinicalTrials) | |||
| CH - Colmar - France | Lionel MOREAU | 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 | |||||
| Angers - CHU - Angers - France | José Hureaux, Dr | Contact (sur clinicalTrials) | |||
| Annemasse - CH - 74100 - Ambilly - France | Philippe ROMAND, Dr | Contact (sur clinicalTrials) | |||
| AP-HM Hôpital Nord - Marseille - France | Pascale TOMASINI | Contact (sur clinicalTrials) | |||
| Avignon - Institut Sainte-Catherine - 84918 - Avignon - France | Alma STANCU, MD | Contact (sur clinicalTrials) | |||
| Bordeaux - Institut Bergonié - Bordeaux - France | Sophie COUSIN, Dr | Contact (sur clinicalTrials) | |||
| Boulogne - Ambroise Paré - Boulogne-Billancourt - France | Etienne GIROUX-LEPRIEUR, MD | Contact (sur clinicalTrials) | |||
| Caen - CHU Côte de Nacre - 14000 - Caen - France | Jeannick MADELAINE, Dr | Contact (sur clinicalTrials) | |||
| Centre Antoine LACASSAGNE - Nice - France | Josiane OTTO, Dr | Contact (sur clinicalTrials) | |||
| Centre Hospitalier Général - Pau - 64000 - Pau - France | Aldo RENAULT, Dr | Contact (sur clinicalTrials) | |||
| Centre Léon Bérard - 69000 - Lyon - France | Maurice Pérol, Dr | Contact (sur clinicalTrials) | |||
| CH Le Mans - Le Mans - France | Camille GUGUEN, Dr | Contact (sur clinicalTrials) | |||
| CHRU de Lille - Lille - France | Alexis CORTOT, Pr | Contact (sur clinicalTrials) | |||
| CHU Charles Nicolle - Rouen - France | Florian GUISIER | Contact (sur clinicalTrials) | |||
| CHU Dupuytren - 87042 - Limoges - France | Thomas Egenod, Dr | Contact (sur clinicalTrials) | |||
| CHU Rennes - Hôpital Pontchaillou - 35033 - Rennes - France | Charles Ricordel, Dr | Contact (sur clinicalTrials) | |||
| CHU Toulouse - Pneumologie - Toulouse - France | Julien Mazieres, Pr | Contact (sur clinicalTrials) | |||
| Hôpital Privé d'Antony - Antony - France | Contact (sur clinicalTrials) | ||||
| Institut Paoli Calmettes - 13273 - Marseille - France | Anne Madroszyk, Dr | Contact (sur clinicalTrials) | |||
| La Roche Sur Yon - CH - 85925 - La Roche Sur Yon - France | Cyril GUIBERT, Dr | Contact (sur clinicalTrials) | |||
| Lyon - URCOT - Pierre-Bénite - France | Sébastien COURAUD, Dr | Contact (sur clinicalTrials) | |||
| Montpellier - CHRU - 34295 - Montpellier - France | Benoit ROCH, Dr | Contact (sur clinicalTrials) | |||
| Mulhouse - GHRMSA - Mulhouse - France | Didier DEBIEUVRE, Dr | Contact (sur clinicalTrials) | |||
| Nancy - Institut de Cancérologie de Lorraine - Nancy - France | Christelle CLEMENT-DUCHENE, Dr | Contact (sur clinicalTrials) | |||
| Nouvel Hôpital Civil - Hôpitaux Universitaires de Strasbourg - 67091 - Strasbourg - France | Céline Mascaux, Pr | Contact (sur clinicalTrials) | |||
| Saint Quentin - CH - 02100 - Saint Quentin - France | Charles Dayen, Dr | Contact (sur clinicalTrials) | |||
| Tours - CHU - 37000 - Tours - France | Delphine CARMIER, Dr | Contact (sur clinicalTrials) | |||
| Villefranche-Sur-Saône - Hôpital Nord-Ouest - Villefranche-Sur-Saône - France | Luc ODIER, Dr | Contact (sur clinicalTrials) | |||
Critères
Tous
Inclusion Criteria:
1. Subjects must have signed and dated an IRB/IEC approved written informed consent
form in accordance with regulatory and institutional guidelines. This must be
obtained before the performance of any protocol related procedures that are not part
of normal subject care.
Subjects must be willing and able to comply with scheduled visits, treatment
schedule, and laboratory testing.
2. Male or female aged at least 18 years old.
3. Histologically confirmed diagnosis of NSCLC that is currently Stage IV (M1a, M1b or
M1c AJCC 8th edition).
4. ECOG performance status of 0-1.
5. Able to swallow and retain oral medication.
6. Presence of a BRAFV600E mutation in lung cancer tissue as determined by a local
laboratory assay.
7. The Investigator must confirm prior to enrolment that the patient has adequate tumor
tissue available to determine BRAFV600E mutation status by central laboratory for
confirmation.
Note: Tumor tissue collected after the patient was diagnosed with metastatic disease
is preferred.
Tumor tissue sample must not be from locations previously radiated. Tumor sample
must be 1 block or 10 to 15 unstained slides of analyzable tissue and one H&E slide.
8. Patients i) (COHORT A) who are either treatment-naïve (e.g., no prior systemic
therapy for advanced/metastatic disease), ii) (COHORT B) who are in progression
after having received 1) first-line platinum-based chemotherapy OR 2) first-line
treatment with an anti-PD-1/L-1 inhibitor given alone or in combination with
platinum-based chemotherapy or in combination with immunotherapy (e.g, ipilimumab)
with or without platinum-based chemotherapy.
Note: Alternative chemotherapy regimens are acceptable if the patient was platinum
intolerant or ineligible.
Patients with early stage disease (e.g., Stages I-III) who have had surgery followed
by chemotherapy (e.g., treatment in the adjuvant setting), and present with new
lesions or evidence of disease recurrence (e.g., metastatic disease), within 12
months of completing chemotherapy, would be considered as had received a first-line
therapy.
Maintenance therapy given after first-line therapy in the metastatic setting will
not be considered a separate regimen, provided there was no documentation of disease
progression between completion of first-line therapy and the start of maintenance
therapy.
9. Presence of measurable disease based on RECIST v1.1.
10. Adequate bone marrow function characterized by the following at screening:
i) ANC ≥ 1.5 × 109/L; ii) Platelets ≥ 100 × 109/L; iii) Hemoglobin ≥ 8.5 g/dL (with
or without blood transfusions).
11. Adequate hepatic and renal function characterized by the following at screening:
i) Total bilirubin ≤ 1.5 × ULN and < 2 mg/dL; OR total bilirubin >1.5 × ULN with
indirect bilirubin < 1.5 × ULN; ii) ALT and AST ≤ 2.5 × ULN, or ≤ 5 × ULN in
presence of liver metastases; iii) Serum creatinine ≤ 1.5 × ULN; or calculated
creatinine clearance ≥ 50 mL/min by Cockcroft-Gault formula; or estimated glomerular
filtration rate>50 mL/min/1.73m2.
12. Female patients of childbearing potential as described in Appendix 1, must have a
negative serum β HCG test result.
13. Female patients of childbearing potential must agree to use methods of contraception
that are highly effective or acceptable, as described in Appendix 1, and to not
donate ova from Screening until 30 days after the last dose of study treatment.
14. Male patients must agree to use methods of contraception that are highly effective
or acceptable, as described in Appendix 1, and to not donate sperm from Screening
until 90 days after the last dose of encorafenib and binimetinib.
15. Patient covered by a national health insurance
1. Subjects must have signed and dated an IRB/IEC approved written informed consent
form in accordance with regulatory and institutional guidelines. This must be
obtained before the performance of any protocol related procedures that are not part
of normal subject care.
Subjects must be willing and able to comply with scheduled visits, treatment
schedule, and laboratory testing.
2. Male or female aged at least 18 years old.
3. Histologically confirmed diagnosis of NSCLC that is currently Stage IV (M1a, M1b or
M1c AJCC 8th edition).
4. ECOG performance status of 0-1.
5. Able to swallow and retain oral medication.
6. Presence of a BRAFV600E mutation in lung cancer tissue as determined by a local
laboratory assay.
7. The Investigator must confirm prior to enrolment that the patient has adequate tumor
tissue available to determine BRAFV600E mutation status by central laboratory for
confirmation.
Note: Tumor tissue collected after the patient was diagnosed with metastatic disease
is preferred.
Tumor tissue sample must not be from locations previously radiated. Tumor sample
must be 1 block or 10 to 15 unstained slides of analyzable tissue and one H&E slide.
8. Patients i) (COHORT A) who are either treatment-naïve (e.g., no prior systemic
therapy for advanced/metastatic disease), ii) (COHORT B) who are in progression
after having received 1) first-line platinum-based chemotherapy OR 2) first-line
treatment with an anti-PD-1/L-1 inhibitor given alone or in combination with
platinum-based chemotherapy or in combination with immunotherapy (e.g, ipilimumab)
with or without platinum-based chemotherapy.
Note: Alternative chemotherapy regimens are acceptable if the patient was platinum
intolerant or ineligible.
Patients with early stage disease (e.g., Stages I-III) who have had surgery followed
by chemotherapy (e.g., treatment in the adjuvant setting), and present with new
lesions or evidence of disease recurrence (e.g., metastatic disease), within 12
months of completing chemotherapy, would be considered as had received a first-line
therapy.
Maintenance therapy given after first-line therapy in the metastatic setting will
not be considered a separate regimen, provided there was no documentation of disease
progression between completion of first-line therapy and the start of maintenance
therapy.
9. Presence of measurable disease based on RECIST v1.1.
10. Adequate bone marrow function characterized by the following at screening:
i) ANC ≥ 1.5 × 109/L; ii) Platelets ≥ 100 × 109/L; iii) Hemoglobin ≥ 8.5 g/dL (with
or without blood transfusions).
11. Adequate hepatic and renal function characterized by the following at screening:
i) Total bilirubin ≤ 1.5 × ULN and < 2 mg/dL; OR total bilirubin >1.5 × ULN with
indirect bilirubin < 1.5 × ULN; ii) ALT and AST ≤ 2.5 × ULN, or ≤ 5 × ULN in
presence of liver metastases; iii) Serum creatinine ≤ 1.5 × ULN; or calculated
creatinine clearance ≥ 50 mL/min by Cockcroft-Gault formula; or estimated glomerular
filtration rate>50 mL/min/1.73m2.
12. Female patients of childbearing potential as described in Appendix 1, must have a
negative serum β HCG test result.
13. Female patients of childbearing potential must agree to use methods of contraception
that are highly effective or acceptable, as described in Appendix 1, and to not
donate ova from Screening until 30 days after the last dose of study treatment.
14. Male patients must agree to use methods of contraception that are highly effective
or acceptable, as described in Appendix 1, and to not donate sperm from Screening
until 90 days after the last dose of encorafenib and binimetinib.
15. Patient covered by a national health insurance
1. Patients with nonsquamous carcinoma who have documentation of any of the following:
EGFR mutation, ALK fusion oncogene or ROS1 rearrangement.
2. Previous treatment with any other BRAF inhibitor (e.g., dabrafenib, vemurafenib...),
or any other MEK inhibitor (e.g., trametinib, cobimetinib...) prior to screening and
enrolment.
4. Patients who have received more than 1 prior line of systemic therapy in the
advanced/metastatic setting for Cohort B.
Note: Generally, treatments that are separated by an event of progression are considered
to represent another line of therapy.
Any therapeutic intervention including systemic therapy, surgery concurrent with or
followed by systemic therapy, radiation concurrent with systemic therapy, or stereotactic
radiation/radiosurgery, initiated or added to an existing therapy for oligometastatic
disease will be considered a new line of therapy.
Palliative radiation to solitary lesions is permitted and will not be considered a new
line of therapy.
Surgery/radiosurgery for CNS metastases is permitted and will not be considered a line of
therapy as long as the surgery/radiosurgery was not given with systemic therapy
(neoadjuvant or adjuvant).
Surgery followed by chemotherapy in the metastatic setting will be considered a line of
therapy.
5. Receipt of anticancer therapies or investigational drugs within the following
intervals before the first administration of study treatment: i) ≤14 days for
chemotherapy, targeted small molecule therapy, radiation therapy, immunotherapy, or
antineoplastic biologic therapy (e.g., erlotinib, crizotinib, bevacizumab etc.).
ii) ≤14 days or 5 half-lives (minimum of 14 days) for investigational agents or devices.
For investigational agents with long half-lives (e.g., > 5 days), enrolment before the
fifth half-life requires sponsor approval.
iii) Palliative radiation therapy must be complete 7 days prior to the first dose of
study treatment.
6. Patients who have had major surgery (e.g., inpatient procedure with regional or
general anesthesia) ≤ 6 weeks prior to start of study treatment.
7. For cohort B : Patient has not recovered to ≤Grade 1 from toxic effects of prior
therapy and/or complications from prior surgical intervention before starting study
treatment.
Note: Stable chronic conditions (≤ Grade 2) that are not expected to resolve (e.g.,
neuropathy, myalgia, alopecia, and prior therapy-related endocrinopathies) are
exceptions.
8. Current use of a prohibited medication (including herbal medications, supplements,
or foods), or use of a prohibited medication ≤1 week prior to the start of study
treatment.
9. Impairment of gastrointestinal function or disease which may significantly alter the
absorption of oral study treatment (e.g., uncontrolled nausea, vomiting or diarrhea,
malabsorption syndrome, small bowel resection).
10. Impaired cardiovascular function or clinically significant cardiovascular diseases,
including any of the following: i) History of acute myocardial infarction, acute
coronary syndromes (including unstable angina, coronary artery bypass graft,
coronary angioplasty or stenting) ≤ 6 months prior to start of study treatment; ii)
Congestive heart failure requiring treatment (New York Heart Association Grade ≥2);
iii) LVEF < 50% as determined by MUGA or ECHO; iv) Uncontrolled hypertension defined
as persistent systolic blood pressure ≥150 mmHg or diastolic blood pressure ≥100
mmHg despite optimal therapy; v) History or presence of clinically significant
cardiac arrhythmias (including uncontrolled atrial fibrillation or uncontrolled
paroxysmal supraventricular tachycardia); vi) Baseline QTcF interval ≥480 ms or a
history of prolonged QT syndrome. 11. History of thromboembolic or cerebrovascular
events ≤12 weeks prior to the first dose of study treatment. Examples include
transient ischemic attacks, cerebrovascular accidents, hemodynamically significant
(i.e. massive or sub-massive) deep vein thrombosis or pulmonary emboli. Note:
Patients with either deep vein thrombosis or pulmonary emboli that does not result
in hemodynamic instability are allowed to enrol as long as they are on a stable dose
of anticoagulants for at least 4 weeks. Note: Patients with thromboembolic events
related to indwelling catheters or other procedures may be enrolled.
12. History or current evidence of RVO (Retinal Vein Occlusion) or current risk factors
for RVO (e.g., uncontrolled glaucoma or ocular hypertension, history of hyper
viscosity or hypercoagulability syndromes); history of retinal degenerative disease.
13. Concurrent neuromuscular disorder that is associated with the potential of elevated
CK (e.g., inflammatory myopathies, muscular dystrophy, amyotrophic lateral
sclerosis, spinal muscular atrophy).
14. Evidence of active, noninfectious pneumonitis, history of interstitial lung disease
that required oral or intravenous glucocorticoid steroids for management.
15. Evidence of HBV or HCV infection. Note: Patients with laboratory evidence of cleared
HBV or HCV infection may be enrolled. Note: Patients with no prior history of HBV
infection who have been vaccinated against HBV and who have a positive antibody
against hepatitis B surface antigen as the only evidence of prior exposure may
enrol.
16. Patient who aas has a known history of a positive test for HIV or known AIDS.
17. Active infection requiring systemic therapy. 18. Patients with symptomatic brain
metastasis, leptomeningeal disease or other active CNS metastases are not eligible.
Note: Patients with previously treated or not treated brain metastases may participate
provided they are stable (e.g., without evidence of progression by radiographic imaging
for at least 28 days before the first dose of study treatment and neurologic symptoms
have returned to baseline) Patients must have no evidence of new or enlarging brain
metastases or CNS edema.
Patient must have discontinued use of steroids at least 7 days before the first dose of
study treatment.
19. Concurrent or previous other malignancy within 2 years of study entry, except
curatively treated basal or squamous cell skin cancer, prostate intraepithelial
neoplasm, carcinoma in-situ of the cervix, Bowen's disease and Gleason 6 prostate
cancer.
20. Known sensitivity or contraindication to any component of study treatment or their
excipients.
21. Pregnancy confirmed by a positive β-HCG laboratory test result, or breastfeeding
(lactating).
22. Other severe, acute or chronic medical or psychiatric condition(s) or laboratory
abnormality that may increase the risk associated with study participation or study
treatment administration or that may interfere with the interpretation of study
results and, in the judgment of the Investigator, would make the patient an
inappropriate candidate for the study.