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Non Small Cell Lung CancerPhase 2ENCO-BRAFNCT04526782

ENCOrafenib With Binimetinib in bRAF NSCLC

A Phase 2 study testing Encorafenib 75 MG and Binimetinib 15 MG in people with Non Small Cell Lung Cancer and BRAF V600E, run by Intergroupe Francophone de Cancerologie Thoracique at 36 sites in France.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial 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 Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Non Small Cell Lung Cancer, BRAF V600E
What is being tested?
Encorafenib 75 MG and Binimetinib 15 MG
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
119 participants
Where
36 sitesFrance
Study dates
19 Jan 2021to Mar 2027
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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.
  • 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.
  • 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.
  • Presence of measurable disease based on RECIST v1.1.
  • Adequate bone marrow function characterized by the following at screening:
  • ANC ≥ 1.5 × 109/L; ii) Platelets ≥ 100 × 109/L; iii) Hemoglobin ≥ 8.5 g/dL (with or without blood transfusions).
  • Adequate hepatic and renal function characterized by the following at screening:
  • 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.
  • Female patients of childbearing potential as described in Appendix 1, must have a negative serum β HCG test result.
  • 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.
  • 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

Who cannot join

  • Patients with nonsquamous carcinoma who have documentation of any of the following: EGFR mutation, ALK fusion oncogene or ROS1 rearrangement.
  • 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.
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  • 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.).
  • ≤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.
  • 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.

Trial locations and contacts

36 sites in 1 country.

36 sites in 1 country

France36 sites

  • Annemasse - CH

    Ambilly, 74100

  • Angers - CHU

    Angers

  • Avignon - Institut Sainte-Catherine

    Avignon, 84918

  • Bordeaux - Institut Bergonié

    Bordeaux

  • Boulogne - Ambroise Paré

    Boulogne-Billancourt

  • Brest - CHU

    Brest

  • Caen - CHU Côte de Nacre

    Caen, 14000

  • CH

    Colmar

  • Centre Hospitalier Intercommunal de Créteil

    Créteil, 94000

  • Centre Georges François Leclerc

    Dijon

  • CHRU Grenoble

    Grenoble

  • La Roche Sur Yon - CH

    La Roche-sur-Yon, 85925

  • CH Le Mans

    Le Mans

  • CHRU de Lille

    Lille

  • CHU Dupuytren

    Limoges, 87042

  • Centre Léon Bérard

    Lyon, 69000

  • Institut Paoli Calmettes

    Marseille, 13273

  • AP-HM Hôpital Nord

    Marseille

  • Montpellier - CHRU

    Montpellier, 34295

  • Mulhouse - GHRMSA

    Mulhouse

  • Nancy - Institut de Cancérologie de Lorraine

    Nancy

  • Centre Antoine LACASSAGNE

    Nice

  • AP-HP Hôpital Cochin

    Paris, 75014

  • AP-HP Hôpital Tenon

    Paris, 75970

  • Hôpital BICHAT

    Paris

  • Paris - Institut Curie

    Paris

  • Centre Hospitalier Général - Pau

    Pau, 64000

  • Lyon - URCOT

    Pierre-Bénite

  • CHU Rennes - Hôpital Pontchaillou

    Rennes, 35033

  • CHU Charles Nicolle

    Rouen

  • Saint Quentin - CH

    Saint-Quentin, 02100

  • Nouvel Hôpital Civil - Hôpitaux Universitaires de Strasbourg

    Strasbourg, 67091

  • CHU Toulouse - Pneumologie

    Toulouse

  • Tours - CHU

    Tours, 37000

  • Villefranche-Sur-Saône - Hôpital Nord-Ouest

    Villefranche-sur-Saône

  • Gustave Roussy

    Villejuif, 94805

Other trials in France

About this study

Official title: 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

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

Being tested
Encorafenib 75 MG, Binimetinib 15 MG
Keywords
encorafenib, binimetinib, NSCLC, IFCT
Medical subject headings
Carcinoma, Non-Small-Cell Lung

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Encorafenib 75 MGDrug

    450 mg (6 × 75 mg capsule) per day

  • Binimetinib 15 MGDrug

    45 mg (3 × 15 mg tablet) twice daily

Study groups in NCT04526782
Study groupRoleWhat they receive
Cohort 1 (1st line)ExperimentalEncorafenib: 450 mg (6 × 75 mg capsule) QD Binimetinib: 45 mg (3 × 15 mg tablet) BID
Receives: Drug: Encorafenib 75 MG; Drug: Binimetinib 15 MG
Cohort 2 (2nd line)ExperimentalEncorafenib: 450 mg (6 × 75 mg capsule) QD Binimetinib: 45 mg (3 × 15 mg tablet) BID
Receives: Drug: Encorafenib 75 MG; Drug: Binimetinib 15 MG

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Objective response rate

    Objective Response Rate at 6 months using RECIST1.1 criteria

    Measured: 6 months

Secondary outcomes (4)

  1. Duration Response Rate

    Time from the date of the first documented response (CR or PR) to the earliest date of disease progression (RECIST 1.1), or death due to any cause.

    Measured: about 12 months

  2. Progression-free Survival

    Time from enrollment to first observation of progression (RECIST1.1) or date of death (from any cause)

    Measured: about 24 months

  3. Overall Survival

    Time from enrollment until death due to any cause

    Measured: about 24 months

  4. Incidence, type and severity of adverse events

    Descriptive statistics of safety will be presented using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 5.0

    Measured: From time of informed consent through treatment period and up to 30 days post last dose of study treatment (about 24 months)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted26 Aug 2020
  2. Study start19 Jan 2021
  3. Primary completion16 Jul 2025
  4. Study completionMar 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Model description
This is an open-label, multicenter, multi-cohort Phase 2 study of the combination of encorafenib and binimetinib in patients with previously treated and untreated BRAFV600E-mutant NSCLC.
Masking
None (open label)
Enrolment
119 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04526782
Sponsor's protocol ID
IFCT-1904
Acronym
ENCO-BRAF
Status last verified
Jul 2026
First submitted
21 Aug 2020
Last updated
11 Aug 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: The individual participant data underlying the results reported in this article, as well as the study protocol and statistical analysis plan, will be made available after deidentification immediately following publication and for three years. Researchers who provide a methodologically sound proposal for any purpose may direct proposals to contact@ifct.fr. To gain access, data requestors will need to sign a data access agreement that requires approval by the French Cooperative Thoracic Intergroup.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Encorafenib 75 MG and Binimetinib 15 MG in people with Non Small Cell Lung Cancer and BRAF V600E, run by Intergroupe Francophone de Cancerologie Thoracique at 36 sites in France.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 23 inclusion and 29 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 11 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 36 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Objective response rate (time frame: 6 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04526782.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Aug 2026.

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