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COMPLETEDPHASE1/PHASE2

Encorafenib + Binimetinib + Pembrolizumab in Patients With Unresectable or Metastatic BRAF V600 Mutant Melanoma

A Randomized Phase I / II Open Label, Multicentre Study of Encorafenib Plus Binimetinib and PD-1 Antibody Pembrolizumab in Patients With Unresectable or Metastatic BRAF V600 Mutant Melanoma

NCT02902042•Prof. Dr. med. Dirk Schadendorf

View on ClinicalTrials.gov

Summary

This study will investigate the influence of maintenance therapy on progression-free survival (PFS) and overall survival (OS) after combination therapy with BRAF/MEK (MAP-ERK kinase) inhibitors and PD-1 antibody pembrolizumab. In the safety phase I part the optimal dose of pembrolizumab in combination with BRAF inhibitor and MEK inhibitor and the safety of this three-drugs-combination regime will be determined. In the randomized part 2 different maintenance therapies will be tested for toxicity and efficacy. Patients with disease control after 6 months of triple therapy will be randomized to receive 2 different maintenance therapies further on, either continuation of triple therapy or administration of pembrolizumab alone.

Detailed Description

There is growing interest to understand the best strategies to use targeted therapies and novel immunotherapy for the treatment of advanced melanoma. This study will explore the combination of encorafenib plus binimetinib with the PD-1 antibody pembrolizumab in patients with BRAF mutant melanoma. Combination of two clinically effective approaches, targeting the mutant BRAF pathway by BRAF/MEK inhibition and modulating immunological checkpoint control by administration of a PD-1 antibody, should prolong PFS and OS even further. This study will investigate the influence of maintenance therapy on PFS and OS after triple therapy. Patients with disease control after 6 months of triple therapy will be randomized to receive 2 different maintenance therapies further on to investigate if administration of pembrolizumab only is sufficient for maintenance of disease control. For reasons of safety a phase I study is performed to determine the optimal dosing and schedule of the combination therapy (encorafenib, binimetinib, pembrolizumab). In the phase II-part, patient will receive triple therapy with the doses defined in phase I for a 6 months induction period. Patients with complete or partial response or stable disease after the 6 months period will be randomized for maintenance therapy: Arm A: Therapy as in induction period. Arm B: Therapy with pembrolizumab only with a dose of 200 mg every 3 weeks.

Eligibility

Age

18 - No limit years

Sex

ALL

Healthy Volunteers

Inclusion Criteria

•Willing and able to provide written informed consent/assent for the trial.
•Being ≥ 18 years of age on day of signing informed consent.
•Histologically confirmed diagnosis of locally advanced, unresectable or metastatic melanoma AJCC (2017) Stage IIIB, IIIC, IIID or IV with no active brain metastasis. All known CNS lesions must have been only treated with stereotactic therapy or surgery at least 4 weeks prior to the first dose of trial treatment AND they are stable (without evidence of progression by imaging for at least 4 weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline); there is no evidence of new or enlarging brain metastases, and the patient must not have used steroids in dosing exceeding 10 mg daily of prednisone equivalent for at least 3 weeks prior to trial treatment.
•Treatment naive patient for locally advanced unresectable or metastatic melanoma. Prior adjuvant or neoadjuvant systemic therapy is permitted (in stage II, III and IV with no evidence of disease) if all related adverse events have either returned to baseline or stabilized.
•(i) Anti-PD-1, anti-CTLA-4, BRAF/MEK inhibitor therapy with at least 6 months between the last dose and date of recurrence.
•(ii) Interferon therapy and chemotherapy with the last dose at least 6 weeks prior to registration.
•(iii) Radiotherapy with the last radiation at least 28 days prior to registration. Participants must have recovered from all radiation-related toxicities. Note: radiated lesions cannot be used as measurable lesions unless there is clear evidence of progression.
•Patients who are in follow-up period of a clinical trial in adjuvant setting may be enrolled.
•Measurable disease, i.e., present with at least one measurable lesion per RECIST, version 1.1, for the definition of a measureable lesion.
•Presence of BRAF mutation V600 in tumor tissue from an archival tissue sample or newly obtained core or excisional biopsy of a tumor lesion prior to enrollment.
+9 more criteria

Exclusion Criteria

•Currently participating in or having participated in a study of an investigational agent or using an investigational device within 4 weeks of the first dose of treatment.
•Diagnosis of immunodeficiency or receiving systemic steroid therapy in dosing exceeding 10 mg daily of prednisone equivalent or any other form of immunosuppressive therapy within 7 days prior to study Day 1.
•Prior therapy (except if given as adjuvant or neoadjuvant therapy for melanoma) with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, anti-CTLA-4 antibody or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways (except for interferon given as adjuvant or neoadjuvant therapy for melanoma).
•Prior therapy (except if given as adjuvant or neoadjuvant therapy for melanoma) with a BRAF inhibitor (including but not limited to vemurafenib, dabrafenib, encorafenib) and / or MEK inhibitor (including but not limited to trametinib, AZD6244, binimetinib, cobimetinib).
•Any previous anti-cancer treatment, extensive radiotherapy or investigational agent for locally advanced unresectable or metastatic melanoma.
•Known additional malignancy that is progressing or required active treatment within 3 years prior to the study.
•Known active CNS metastases and/or carcinomatous meningitis.
•Presence of uveal melanoma.
•History of leptomeningeal metastases.
•History or current evidence of CSR or RVO or predisposing factors to RVO or CSR (e.g. uncontrolled glaucoma or ocular hypertension, uncontrolled diabetes mellitus, history of hyperviscosity or hypercoagulability syndromes).
+16 more criteria

Locations (11)

Universitätsklinikum Freiburg

Freiburg im Breisgau, Baden-Wurttemberg, Germany

Klinikum Augsburg Süd

Augsburg, Bavaria, Germany

Klinikum rechts der Isar

München, Bavaria, Germany

Klinikum Nürnberg Nord

Nuremberg, Bavaria, Germany

Universitätsklinikum Gießen und Marburg GmbH, Klinik für Dermatologie und Allergologie

Giessen, Hesse, Germany

Universitätsklinikum der RWTH Aachen

Aachen, North Rhine-Westphalia, Germany

University Hospital Essen, Department of Dermatology, Skin Cancer Center

Essen, North Rhine-Westphalia, Germany

HELIOS Klinikum Krefeld

Krefeld, North Rhine-Westphalia, Germany

Gesellschaft für Klinische Forschung Ludwigshafen mbH

Ludwigshafen am Rhein, Rhineland-Palatinate, Germany

Städtisches Klinikum Dessau

Dessau, Saxony-Anhalt, Germany

Key Dates

Start Date

April 24, 2018

Primary Completion Date

November 30, 2020

Completion Date

November 30, 2020

Last Updated

February 16, 2021

Enrollment

ACTUAL participants

Conditions

Malignant Melanoma

Interventions

Encorafenib

DRUG

Binimetinib

DRUG

Pembrolizumab

DRUG

Pembrolizumab alone

DRUG

An Phase Ib/II Clinical Trial of TCC1727 Combination Therapy in Advanced Solid Tumors

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Solid CancersNSCLC (Advanced Non-small Cell Lung Cancer)+3 more

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RECRUITINGPHASE1/PHASE2

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Malignant Melanoma

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Data Source & Attribution

This clinical trial information is sourced from ClinicalTrials.gov, a service of the U.S. National Institutes of Health.

ClinicalTrials.gov last update: February 16, 2021Data synced to Clareo: March 29, 2026

Modifications: This data has been reformatted for display purposes. Eligibility criteria have been parsed into inclusion/exclusion sections. Location data has been geocoded to enable distance-based search. For the authoritative and most current information, please visit ClinicalTrials.gov.

Neither the United States Government nor Clareo Health make any warranties regarding the data. Check ClinicalTrials.gov frequently for updates.

View ClinicalTrials.gov Terms and Conditions

Encorafenib + Binimetinib + Pembrolizumab in Patients With Unresectable or Metastatic BRAF V600 Mutant Melanoma

Inclusion Criteria

Exclusion Criteria

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