Encorafenib + Binimetinib + Pembrolizumab in Patients With Unresectable or Metastatic BRAF V600 Mutant Melanoma (IMMU-TARGET)
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|ClinicalTrials.gov Identifier: NCT02902042|
Recruitment Status : Recruiting
First Posted : September 15, 2016
Last Update Posted : November 1, 2019
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.
|Condition or disease||Intervention/treatment||Phase|
|Malignant Melanoma||Drug: Encorafenib Drug: Binimetinib Drug: Pembrolizumab Drug: Pembrolizumab alone||Phase 1 Phase 2|
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||145 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||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|
|Actual Study Start Date :||April 24, 2018|
|Estimated Primary Completion Date :||September 2023|
|Estimated Study Completion Date :||October 2023|
Experimental: Arm A: Triple therapy
Encorafenib, binimetinib and pembrolizumab. Doses as determined in phase I
Dose determined in phase I. Start dose: 450 mg qd
Other Name: Braftovi
Dose determined in phase I. Start dose: 45 mg bid
Other Name: Mektovi
Dose determined in phase I. Start dose: 200 mg q3w
Other Name: Keytruda
Experimental: Arm B: Pembrolizumab alone
Pembrolizumab with a dose of 200 mg every 3 weeks.
Drug: Pembrolizumab alone
200 mg q3w
Other Name: Keytruda
- Phase I: Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability of the triple combination treatment] [ Time Frame: 42 days ]Dose limiting toxicities (DLT) will be determined within 42 days of therapy start (first pembrolizumab injection) and are defined as all ≥ grade 4 hematological toxicities and certain non-hematological toxicities ≥ CTCAE grade 3.
- Phase II: Progression-free survival (PFS) [ Time Frame: 24 months ]Time from administration of first study drug to the date of first documented progression (according Recist criteria version 1.1) or death due to any cause, whichever occurs first.
- Phase II: PFS rate at 12 months [ Time Frame: 12 months ]Rate of patients with PFS after 12 months of therapy
- Phase II: PFS rate at 18 months [ Time Frame: 18 months ]Rate of patients with PFS after 18 months of therapy
- Phase II: PFS rate at 24 months [ Time Frame: 24 months ]Number of patients with PFS after 24 months of therapy
- Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] [ Time Frame: 24 months ]All adverse events (AEs) / serious adverse events (SAEs) NCI CTCEA (Common Terminology Criteria for Adverse Events) Grade ≥ 3
- Objective response rate [ Time Frame: 24 months ]Number of patients with complete response (CR), partial response (PR) and stable disease (SD) as best response.
- Overall survival time [ Time Frame: 24 months ]Time from the date of first administration of study drug to the date of death due to any cause.
- 1-year survival rate [ Time Frame: 12 months ]Number of patients alive in the time period from date of first administration of study drug until 1 year after date of first administration
- 2-year survival rate [ Time Frame: 24 months ]Number of patients alive in the time period from date of first administration of study drug until 2 years after date of first administration
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02902042
|Contact: Dirk Schadendorf, Prof. Dr.||+49 (0) 201-723 ext firstname.lastname@example.org|
|Universitätsklinikum Freiburg||Active, not recruiting|
|Freiburg, Baden-Württemberg, Germany, 79106|
|Klinikum Augsburg Süd||Not yet recruiting|
|Augsburg, Bavaria, Germany, 86179|
|Principal Investigator: Christiane Pfeiffer, PD Dr. med.|
|Klinikum rechts der Isar||Recruiting|
|München, Bavaria, Germany, 81675|
|Principal Investigator: Angela Krackhardt, Prof.Dr.med.|
|Klinikum Nürnberg Nord||Recruiting|
|Nürnberg, Bavaria, Germany, 90419|
|Principal Investigator: Erwin S. Schultz, Prof.Dr.med.|
|Vivantes Klinikum im Friedrichshain||Active, not recruiting|
|Berlin Friedrichshain, Berlin, Germany, 10249|
|Universitätsklinikum Gießen und Marburg GmbH, Klinik für Dermatologie und Allergologie||Recruiting|
|Gießen, Hessen, Germany, 35392|
|Principal Investigator: Göppner Daniela, PD Dr. med.|
|Universitätsklinikum der RWTH Aachen||Not yet recruiting|
|Aachen, Nordrhein-Westfalen, Germany, 52074|
|Principal Investigator: Albert Rübben, Prof.Dr.med.|
|University Hospital Essen, Department of Dermatology, Skin Cancer Center||Recruiting|
|Essen, North Rhine-Westphalia, Germany, 45122|
|Contact: Dirk Schadendorf, Prof. Dr. +49 (0) 201-723 ext 4342 email@example.com|
|Principal Investigator: Dirk Schadendorf, Prof. Dr.|
|Sub-Investigator: Lisa Zimmer, Dr. med.|
|Sub-Investigator: Elisabeth Livingstone, Dr. med.|
|HELIOS Klinikum Krefeld||Active, not recruiting|
|Krefeld, North Rhine-Westphalia, Germany, 47805|
|Gesellschaft für Klinische Forschung Ludwigshafen mbH||Not yet recruiting|
|Ludwigshafen am Rhein, Rheinland-Pfalz, Germany, 67063|
|Principal Investigator: Edgar Dippel, Prof.Dr.med.|
|Städtisches Klinikum Dessau||Active, not recruiting|
|Dessau, Saxony-Anhalt, Germany, 06847|
|Principal Investigator:||Dirk Schadendorf, Prof. Dr.||University Hospital, Essen|