NCT04526782

Brief 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

Trial Health

55
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
119

participants targeted

Target at P50-P75 for phase_2

Timeline
Completed

Started Jan 2021

Longer than P75 for phase_2

Geographic Reach
1 country

36 active sites

Status
active not recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

August 21, 2020

Completed
5 days until next milestone

First Posted

Study publicly available on registry

August 26, 2020

Completed
5 months until next milestone

Study Start

First participant enrolled

January 19, 2021

Completed
4.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 16, 2025

Completed
8 months until next milestone

Study Completion

Last participant's last visit for all outcomes

March 1, 2026

Completed
Last Updated

November 18, 2025

Status Verified

November 1, 2025

Enrollment Period

4.5 years

First QC Date

August 21, 2020

Last Update Submit

November 14, 2025

Conditions

Keywords

encorafenibbinimetinibNSCLCIFCT

Outcome Measures

Primary Outcomes (1)

  • Objective response rate

    Objective Response Rate at 6 months using RECIST1.1 criteria

    6 months

Secondary Outcomes (4)

  • Duration Response Rate

    about 12 months

  • Progression-free Survival

    about 24 months

  • Overall Survival

    about 24 months

  • Incidence, type and severity of adverse events

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

Study Arms (2)

Cohort 1 (1st line)

EXPERIMENTAL

Encorafenib: 450 mg (6 × 75 mg capsule) QD Binimetinib: 45 mg (3 × 15 mg tablet) BID

Drug: Encorafenib 75 MGDrug: Binimetinib 15 MG

Cohort 2 (2nd line)

EXPERIMENTAL

Encorafenib: 450 mg (6 × 75 mg capsule) QD Binimetinib: 45 mg (3 × 15 mg tablet) BID

Drug: Encorafenib 75 MGDrug: Binimetinib 15 MG

Interventions

450 mg (6 × 75 mg capsule) per day

Cohort 1 (1st line)Cohort 2 (2nd line)

45 mg (3 × 15 mg tablet) twice daily

Cohort 1 (1st line)Cohort 2 (2nd line)

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.
  • 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.
  • +8 more criteria

You may not qualify if:

  • 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.
  • \. 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.
  • \. 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.
  • \. 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 foods), or use of a prohibited medication ≤1 week prior to the start of study treatment.
  • +14 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (36)

Annemasse - CH

Ambilly, 74100, France

Location

Angers - CHU

Angers, France

Location

Avignon - Institut Sainte-Catherine

Avignon, 84918, France

Location

Bordeaux - Institut Bergonié

Bordeaux, France

Location

Boulogne - Ambroise Paré

Boulogne-Billancourt, France

Location

Brest - CHU

Brest, France

Location

Caen - CHU Côte de Nacre

Caen, 14000, France

Location

CH

Colmar, France

Location

Centre Hospitalier Intercommunal de Créteil

Créteil, 94000, France

Location

Centre Georges François Leclerc

Dijon, France

Location

CHRU Grenoble

Grenoble, France

Location

La Roche Sur Yon - CH

La Roche-sur-Yon, 85925, France

Location

CH Le Mans

Le Mans, France

Location

CHRU de Lille

Lille, France

Location

CHU Dupuytren

Limoges, 87042, France

Location

Centre Léon Bérard

Lyon, 69000, France

Location

Institut Paoli Calmettes

Marseille, 13273, France

Location

AP-HM Hôpital Nord

Marseille, France

Location

Montpellier - CHRU

Montpellier, 34295, France

Location

Mulhouse - GHRMSA

Mulhouse, France

Location

Nancy - Institut de Cancérologie de Lorraine

Nancy, France

Location

Centre Antoine LACASSAGNE

Nice, France

Location

AP-HP Hôpital Cochin

Paris, 75014, France

Location

AP-HP Hôpital Tenon

Paris, 75970, France

Location

Hôpital BICHAT

Paris, France

Location

Paris - Institut Curie

Paris, France

Location

Centre Hospitalier Général - Pau

Pau, 64000, France

Location

Lyon - URCOT

Pierre-Bénite, France

Location

CHU Rennes - Hôpital Pontchaillou

Rennes, 35033, France

Location

CHU Charles Nicolle

Rouen, France

Location

Saint Quentin - CH

Saint-Quentin, 02100, France

Location

Nouvel Hôpital Civil - Hôpitaux Universitaires de Strasbourg

Strasbourg, 67091, France

Location

CHU Toulouse - Pneumologie

Toulouse, France

Location

Tours - CHU

Tours, 37000, France

Location

Villefranche-Sur-Saône - Hôpital Nord-Ouest

Villefranche-sur-Saône, France

Location

Gustave Roussy

Villejuif, 94805, France

Location

Related Links

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

encorafenibbinimetinib

Condition Hierarchy (Ancestors)

Carcinoma, BronchogenicBronchial NeoplasmsLung NeoplasmsRespiratory Tract NeoplasmsThoracic NeoplasmsNeoplasms by SiteNeoplasmsLung DiseasesRespiratory Tract Diseases

Study Officials

  • David Planchard

    Gustave Roussy (Villejuif - France)

    PRINCIPAL INVESTIGATOR
  • Charles Ricordel

    CHU Rennes,France

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Model Details: 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.
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

August 21, 2020

First Posted

August 26, 2020

Study Start

January 19, 2021

Primary Completion

July 16, 2025

Study Completion

March 1, 2026

Last Updated

November 18, 2025

Record last verified: 2025-11

Data Sharing

IPD Sharing
Will share

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.

Locations