Binimetinib Plus Encorafenib Real Life Investigation of Next Generation Melanoma Treatment

Study Overview
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Brief Summary
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BERING-MELANOMA - designed as a prospective, longitudinal, non-interventional study - investigates real-world effectiveness, quality of life, safety and tolerability of encorafenib plus binimetinib in unresectable advanced or metastatic BRAF(Rapidly Accelerated Fibrosarcoma isoform B)-V600-mutant malignant melanoma after commercial availability of these two products in Germany, Austria and Switzerland. The study focusses on the documentation of the first and second line setting (i.e. after one line of prior checkpoint inhibition) by documenting patients treated according to the SmPC (Summary of Product Characteristics).

Official Title
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Encorafenib Plus Binimetinib in Patients With Locally Advanced, Unresectable or Metastatic BRAFV600-mutated Melanoma: a Multi-centric, Multinational, Prospective, Longitudinal, Non-interventional Study in Germany, Austria and Switzerland - BERING MELANOMA

Conditions
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Melanoma Stage IV, Melanoma Stage III

Intervention / Treatment
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* Drug: Encorafenib
* Drug: Binimetinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent of the patient with regard to the pseudonymized documentation as well as the transfer and processing of his/her data within the study and the ADOREG [Cancer Registry of German Working Group of Dermato-Oncology] registry (data transfer to ADOREG registry only for patients from German sites); Legally capable male or female patient ≥ 18 years of age (no upper limit); Decision was taken to treat the patient with encorafenib plus binimetinib in accordance with the current SmPC [Summary of Product Characteristics] and by prescription; this decision was taken prior to and independent from the inclusion into the study; Treatment with encorafenib plus binimetinib has been started ≤ 6 months prior to providing written informed consent for this study or is planned to be started in the near future; Unresectable advanced or metastatic malignant melanoma with BRAF [Rapidly Accelerated Fibrosarcoma isoform B] V600 mutation; Treatment-naive or after one prior line of checkpoint inhibitor treatment (anti-CTLA4 [Cytotoxic T-Lymphocyte Antigen-4] and/or anti-PD(L)1 [Programmed cell Death protein 1]) in the unresectable advanced or metastatic setting. Exclusion Criteria: Previous treatment with a BRAF- and/or MEK [Mitogen-Activated Protein/Extracellular-signal Regulated Kinase]- inhibitor except for: -- prior adjuvant treatment with BRAF+MEK-inhibitor combination therapy that ended > 6 months prior start of Encorafenib/Binimetinib treatment; More than one prior line of checkpoint inhibitor treatment in the unresectable advanced or metastatic setting; Any previous chemotherapeutic treatment of the melanoma disease; Presence of any contraindication with regard to the encorafenib-binimetinib-treatment as specified in the corresponding SmPCs; Current or upcoming participation in an interventional clinical trial; Current or upcoming systemic treatment of any other tumor than melanoma; Prisoners or persons who are compulsorily detained (involuntarily incarcerated).

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Encorafenib|Observation of real-life treatment with encorafenib and binimetinib|
|Drug: Binimetinib|Observation of real-life treatment with encorafenib and binimetinib|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival | Progression-free survival rate | At 12 months after start of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patient and disease profiles at start of treatment with encorafenib plus binimetinib | Demographic and disease characteristics | Baseline | 
| Type of treatments before and after encorafenib plus binimetinib | Treatment sequence prior to and after encorafenib plus binimetinib; by documenting pre-treatments with adjuvant therapy and systemic therapy in palliative setting; and by documenting subsequent systemic treatment lines after administration of encorafenib plus binimetinib | Complete observation time-frame (the total observation period of this study will amount to 90 months). | 
| Sequence of treatments before and after encorafenib plus binimetinib | Treatment sequence prior to and after encorafenib plus binimetinib; by documenting pre-treatments with adjuvant therapy and systemic therapy in palliative setting; and by documenting subsequent systemic treatment lines after administration of encorafenib plus binimetinib | Complete observation time-frame (the total observation period of this study will amount to 90 months). | 
| Characteristics of treatment with encorafenib plus binimetinib | Evaluation of reason for treatment selection (efficacy, safety profile, quality of life, patients preference, physician's preference, comorbidities, other) | From start to end of treatment (anticipated median treatment duration ca. 12 months) | 
| Effectiveness of treatment with encorafenib plus binimetinib | Further progression-free survival parameters | From start to end of treatment (anticipated median treatment duration ca. 12 months) | 
| Effectiveness of treatment with encorafenib plus binimetinib | Time-to-progression | From start to end of treatment (anticipated median treatment duration ca. 12 months) | 
| Effectiveness of treatment with encorafenib plus binimetinib | Best observed tumor response | From start to end of treatment (anticipated median treatment duration ca. 12 months) | 
| Effectiveness of treatment with encorafenib plus binimetinib | Overall response rate | From start to end of treatment (anticipated median treatment duration ca. 12 months) | 
| Effectiveness of treatment with encorafenib plus binimetinib | Duration of response | From start to end of treatment (anticipated median treatment duration ca. 12 months) | 
| Effectiveness of treatment with encorafenib plus binimetinib | Disease control rate | From start to end of treatment (anticipated median treatment duration ca. 12 months) | 
| Effectiveness of treatment with encorafenib plus binimetinib | Duration of disease control | From start to end of treatment (anticipated median treatment duration ca. 12 months) | 
| Effectiveness of treatment with encorafenib plus binimetinib | Overall survival | Complete observation time-frame (the total observation period of this study will amount to 90 months). | 
| Patient reported outcomes during treatment with encorafenib plus binimetinib - evaluated with EORTC QLQ C-30 | EORTC QLQ C-30 questionnaires (European Organisation for Research and Treatment of Cancer Quality of Life C-30 questionnaires) to assess quality of life of cancer patients; comprises 30 items, 24 of which are aggregated into nine multi-item scales, that is, five functioning scales (physical, role, cognitive, emotional and social), three symptom scales (fatigue, pain and nausea/vomiting) and one global health status scale. The remaining six single-item (dyspnoea, appetite loss, sleep disturbance, constipation, diarrhoea and the financial impact) scales assess symptoms. | From start to end of treatment (anticipated median treatment duration ca. 12 months) | 
| Patient reported outcomes during treatment with encorafenib plus binimetinib evaluated with WPAI | WPAI questionnaires (Work Productivity and Activity Impairment questionnaires). The following questions ask about the effect of patients melanoma on the ability to work and perform regular activities. Are you currently employed (working for pay)? During the past seven days, how many hours did you miss from work because of problems associated with your melanoma? During the past seven days, how many hours did you miss from work because of any other reason? During the past seven days, how many hours did you actually work? During the past seven days, how much did your melanoma affect your productivity while you were working? During the past seven days, how much did your melanoma affect your ability to do your regular daily activities, other than work at a job? | From start to end of treatment (anticipated median treatment duration ca. 12 months) | 
| Patient reported outcomes during treatment with encorafenib plus binimetinib evaluated with CTSQ | CTSQ questionnaires (Cancer Therapy Satisfaction Questionnaire) to assess patients' opinions and feelings concerning their cancer therapy and associated adverse events: Questions to patients thoughts about cancer therapy (IV/pills). Scale: [Always, Most of the time, Some-times, Rarely, Never]; Questions to patients satisfaction with the most recent cancer therapy (IV/pills): Scale reg. benefit: [Much better than my expectations Somewhat better than my expectations, Met my expectations, Somewhat worse than my expectations, Much worse than my expectations]; Scale reg. side effects: [Much better than I expected, Somewhat better than I expected, Exactly as I expected, Somewhat worse than I expected, Much worse than I expected]; Scale reg. satisfaction: [Very satisfied, Satisfied, Neither satisfied nor dissatisfied, Dissatisfied, Very dissatisfied]; Scale reg. choice of therapy: [Yes, definitely, Probably Yes, I don't know, Probably not, Definitely not] | From start to end of treatment (anticipated median treatment duration ca. 12 months) | 
| Physicians' satisfaction with regard the treatment with encorafenib plus binimetinib | Physicians' satisfaction questionnaires (measuring Physician's Satisfaction with regard to Effictiveness and Safety, as well as Physician's Overall Treatment Satisfaction) using the following scale construct: Physician's Satisfaction with regard to Efficiency Physician's Satisfaction with regard to Safety Physician's Overall Treatment Satisfaction Scale: very dissatisfied dissatisfied moderately satisfied satisfied very satisfied | From start to end of treatment (anticipated median treatment duration ca. 12 months) | 
| Safety and tolerability of treatment with encorafenib plus binimetinib - Adverse events and adverse reactions including time to onset and time to resolution | Number of patients with Adverse Events and maximum grade per patient, Adverse Drug Reactions, Adverse Drug Reactions grade 3/4, Serious Adverse Events, Serious Adverse Drug Reactions. | Complete observation time-frame (the total observation period of this study will amount to 90 months). | 
| Prognostic factors | Influence of prognostic factors on quality of life outcome parameters | Complete observation time-frame (the total observation period of this study will amount to 90 months). | 
| Prognostic factors | Influence of prognostic factors on effectiveness | Complete observation time-frame (the total observation period of this study will amount to 90 months). | 
| Prognostic factors | Influence of prognostic factors on safety | Complete observation time-frame (the total observation period of this study will amount to 90 months). | 
| Treatment duration | From date of first treatment (encorafenib or binimetinib, whichever occurs first) until date of last treatment (encorafenib or binimetinib, whichever occurs last) | From start to end of treatment (anticipated median treatment duration ca. 12 months) | 
| Treatment dose intensity | From date of first treatment (encorafenib or binimetinib, whichever occurs first) until date of last treatment (encorafenib or binimetinib, whichever occurs last) | From start to end of treatment (anticipated median treatment duration ca. 12 months) | 
| Number of treatment interruptions | From date of first treatment (encorafenib or binimetinib, whichever occurs first) until date of last treatment (encorafenib or binimetinib, whichever occurs last) | From start to end of treatment (anticipated median treatment duration ca. 12 months) | 
| Duration of treatment interruptions | From date of first treatment (encorafenib or binimetinib, whichever occurs first) until date of last treatment (encorafenib or binimetinib, whichever occurs last) | From start to end of treatment (anticipated median treatment duration ca. 12 months) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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BERING, Encorafenib, Binimetinib