ENCOrafenib With Binimetinib in bRAF NSCLC (ENCO-BRAF)

  • STATUS
    Recruiting
  • End date
    Mar 14, 2026
  • participants needed
    119
  • sponsor
    Intergroupe Francophone de Cancerologie Thoracique
Updated on 14 July 2022
systemic therapy
measurable disease
BRAF
docetaxel
cancer chemotherapy
platinum-based chemotherapy
kidney function test
lung carcinoma

Summary

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

Details
Condition Non Small Cell Lung Cancer, BRAF V600E
Treatment docetaxel, Encorafenib 75 MG, Binimetinib 15 MG
Clinical Study IdentifierNCT04526782
SponsorIntergroupe Francophone de Cancerologie Thoracique
Last Modified on14 July 2022

Eligibility

Yes No Not Sure

Inclusion Criteria

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
Male or female aged at least 18 years old
Histologically confirmed diagnosis of NSCLC that is currently Stage IV (M1a, M1b or M1c AJCC 8th edition)
ECOG performance status of 0-1
Able to swallow and retain oral medication
Presence of a BRAFV600E mutation in lung cancer tissue as determined by a local laboratory assay
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
sample must be 1 block or 10 to 15 unstained slides of analyzable tissue and
Note: Tumor tissue collected after the patient was diagnosed with metastatic
one H&E slide
disease is preferred
Patients i) (COHORT A) who are either treatment-naïve (e.g., no prior systemic therapy for advanced/metastatic disease), ii) (COHORT B) who have 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
Tumor tissue sample must not be from locations previously radiated. Tumor
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
Presence of measurable disease based on RECIST v1.1
present with new lesions or evidence of disease recurrence (e.g., metastatic
Adequate bone marrow function characterized by the following at screening
disease), within 12 months of completing chemotherapy, would be considered as
ANC ≥ 1.5 × 109/L; ii) Platelets ≥ 100 × 109/L; iii) Hemoglobin ≥ 8.5 g/dL (with or without blood transfusions)
had received a first-line therapy
Adequate hepatic and renal function characterized by the following at screening
Maintenance therapy given after first-line therapy in the metastatic setting
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
will not be considered a separate regimen, provided there was no documentation
Female patients of childbearing potential as described in Appendix 1, must have a negative serum β HCG test result
of disease progression between completion of first-line therapy and the start
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
of maintenance therapy
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
Patient covered by a national health insurance

Exclusion Criteria

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
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
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
Patients with nonsquamous carcinoma who have documentation of any of the following: EGFR mutation, ALK fusion oncogene or ROS1 rearrangement
fifth half-life requires sponsor approval
iii) Palliative radiation therapy must be complete 7 days prior to the first dose of study
treatment
Patients who have received more than 1 prior line of systemic therapy in the advanced/metastatic setting for Cohort B
Patients who have had major surgery (e.g., inpatient procedure with regional or general
anesthesia) ≤ 6 weeks prior to start of study treatment
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
Current use of a prohibited medication (including herbal medications, supplements, or
therapy
foods), or use of a prohibited medication ≤1 week prior to the start of study treatment
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)
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
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
Concurrent neuromuscular disorder that is associated with the potential of elevated CK
(e.g., inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis, spinal
muscular atrophy)
Evidence of active, noninfectious pneumonitis, history of interstitial lung disease
that required oral or intravenous glucocorticoid steroids for management
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
Patient who aas has a known history of a positive test for HIV or known AIDS
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
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
Known sensitivity or contraindication to any component of study treatment or their
excipients
Pregnancy confirmed by a positive β-HCG laboratory test result, or breastfeeding
(lactating)
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
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