Surgical or Radiotherapeutic Intervention Concerning Large Singular Stable to Progressive Metastases in Patients With BRAFV600-mutated Melanoma Receiving Treatment With Encorafenib + Binimetinib

NCT07092410 | Withdrawn Phase 4

• 2 other identifiers: WKG 139175-522024-516073-74-00
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is an open-label, prospective, single arm study conducted in Germany to investigate local treatment (i.e. surgery or radiotherapy or electrochemotherapy) of metastases showing no response to encorafenib (E) + binimetinib (B) combination therapy and continuation of EB therapy afterwards. The purpose of this study is to determine PFS of individual patients treated with local intervention while continuing therapy with EB.

Conditions

Melanoma BRAF V600E/K Mutated

Keywords

BRAFV600-mutated; Melanoma; Encorafenib; Binimetinib; BRAF inhibitor; MEK inhibitor; Braftovi; Mektovi

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival (PFS) after local treatment (radiotherapy / surgery / electrochemotherapy)

  The purpose of this study is to determine PFS of individual patients treated with local intervention while continuing therapy with EB.

  From enrollment up to end of treatment period after 52 weeks maximum.

Secondary Outcomes (6)

• Overall Response Rate (ORR), Disease Control Rate (DCR), Duration of Response (DoR), Duration of Disease Control (DoDC), Duration of Stable Disease (DoSD)

  From enrollment up to end of treatment period after 52 weeks maximum.

• progression-free survival rate (PFSR) at 1 year after local treatment (radiotherapy / surgery /electrochemotherapy)

  From enrollment up to end of treatment period after 52 weeks maximum.

• time to treatment failure (TTF)

  From enrollment up to end of treatment period after 52 weeks maximum.

• overall survival (OS)

  From enrollment up to end of treatment period after 52 weeks maximum.

• Quality of Life (QoL)

  From enrollment up to end of treatment period after 52 weeks maximum.

Study Arms (1)

Single arm study. Surgery or radiotherapy or electrochemotherapy in melanoma patients receiving IMP

OTHER

Local intervention (surgery or radiotherapy or electrochemotherapy) concerning large singular stable to progressive metastases in patients with BRAFV600-mutated melanoma receiving treatment with Encorafenib + Binimetinib

Drug: Encorafenib & Binimetinib Treatment

Interventions

Encorafenib & Binimetinib Treatment DRUG

The SuRage-EB post approval study will evaluate prospectively the potential impact of local treatment of melanoma metastases under encorafenib (E) + binimetinib (B) combination therapy while continuing EB therapy thereafter. It focusses on single melanoma metastases which develop resistance or show no response during EB treatment. These metastases will be treated locally before registration of the patients into the study. Directly after or during local treatment, EB combination therapy will be resumed. Locally treated EB-resistant melanoma cells cannot continue to grow during targeted therapy and the positive response may be prolonged.

Also known as: Braftovi®, Mektovi®

Single arm study. Surgery or radiotherapy or electrochemotherapy in melanoma patients receiving IMP

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients may be included in the study only if they meet all the following criteria:
• Signed informed consent form
• Female and male patients ≥ 18 years of age
• Ability to comply with the study protocol, in the investigator's judgement
• Ongoing treatment with Encorafenib plus Binimetinib (EB) in accordance with the current Summary of Product Characteristics (SmPC) for a minimum of 3 months
• ECOG performance status 0-2
• Life expectancy ≥ 12 weeks
• Histologically confirmed diagnosis of locally advanced, unresectable or metastatic cutaneous or unknown primary melanoma (inoperable stage III or metastatic stage IV, per AJCC 8 staging)
• Presence of a BRAFV600-mutation according to a validated test
• Measurable disease according to RECIST v.1.1, i.e. 1 to 3 locally untreated target lesion(s) to treat with a longest diameter of ≥ 10 mm (lymph node metastases smallest diameter ≥ 15 mm) \[TLT; target lesion(s) to treat which are stable or progressive under EB and subject to surgery or electrochemotherapy or radiotherapy within the study\] plus ≥ 1 additional target lesion \[target lesion(s), which are not subject to surgery or electrochemotherapy or radiotherapy within the study\] for continuous measurement Note: Localization of TLTs will be cohortly observed.
• Availability of RECIST-v1.1-compliant imaging (CT or MRT chest/ abdomen/pelvis and MRT head) within 28 days before initiation of EB treatment outside of the study (= "EB pretreatment") and within 28 days before initiation of surgery or electrochemotherapy or radiotherapy, to assess treatment response under EB pretreatment Note: Steering committee approval is required for older imaging (however, imaging older than 2 months prior to EB initiation is not allowed).
• Patient must fulfill one of the following conditions (= mixed tumor response) for TLT:
• EB in palliative 1st line i. with current response of all metastases according to RECIST v1.1 with exception of 1 to 3 TLT that are stable ii. with current response or stability of all metastases according to RECIST v1.1 with exception of 1 to 3 TLT that are progressing
• EB in palliative 2nd line after progression upon checkpoint inhibition in palliative 1st line i. with current response of all metastases according to RECIST v1.1 with the exception of 1 to 3 TLT that are stable ii. with current response or stability of all metastases according to RECIST v1.1 with the exception of 1 to 3 TLT that are progressing
• Notes:

You may not qualify if:

• Patients may be included in the study only if they meet all the following criteria:
• Signed informed consent form
• Female and male patients ≥ 18 years of age
• Ability to comply with the study protocol, in the investigator's judgement
• Ongoing treatment with Encorafenib plus Binimetinib (EB) in accordance with the current Summary of Product Characteristics (SmPC) for a minimum of 3 months
• ECOG performance status 0-2
• Life expectancy ≥ 12 weeks
• Histologically confirmed diagnosis of locally advanced, unresectable or metastatic cutaneous or unknown primary melanoma (inoperable stage III or metastatic stage IV, per AJCC 8 staging)
• Presence of a BRAFV600-mutation according to a validated test
• Measurable disease according to RECIST v.1.1, i.e. 1 to 3 locally untreated target lesion(s) to treat with a longest diameter of ≥ 10 mm (lymph node metastases smallest diameter ≥ 15 mm) \[TLT; target lesion(s) to treat which are stable or progressive under EB and subject to surgery or electrochemotherapy or radiotherapy within the study\] plus ≥ 1 additional target lesion \[target lesion(s), which are not subject to surgery or electrochemotherapy or radiotherapy within the study\] for continuous measurement Note: Localization of TLTs will be cohortly observed.
• Availability of RECIST-v1.1-compliant imaging (CT or MRT chest/ abdomen/pelvis and MRT head) within 28 days before initiation of EB treatment outside of the study (= "EB pretreatment") and within 28 days before initiation of surgery or electrochemotherapy or radiotherapy, to assess treatment response under EB pretreatment Note: Steering committee approval is required for older imaging (however, imaging older than 2 months prior to EB initiation is not allowed).
• Patient must fulfill one of the following conditions (= mixed tumor response) for TLT:
• EB in palliative 1st line i. with current response of all metastases according to RECIST v1.1 with exception of 1 to 3 TLT that are stable ii. with current response or stability of all metastases according to RECIST v1.1 with exception of 1 to 3 TLT that are progressing
• EB in palliative 2nd line after progression upon checkpoint inhibition in palliative 1st line i. with current response of all metastases according to RECIST v1.1 with the exception of 1 to 3 TLT that are stable ii. with current response or stability of all metastases according to RECIST v1.1 with the exception of 1 to 3 TLT that are progressing
• Notes:

Sponsors & Collaborators

• SRH Wald-Klinikum Gera GmbH: lead
• Pierre Fabre Pharma GmbH: collaborator

MeSH Terms

Conditions

Melanoma

Interventions

encorafenib; binimetinib

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Martin Kaatz, PD Dr. med. habil.

  SRH Wald-Klinikum Gera GmbH

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: The purpose of this study is to determine PFS (Progression free survival) of individual patients treated with local intervention while continuing therapy with EB.

Study Record Dates

• First Submitted: July 7, 2025
• First Posted: July 29, 2025
• Study Start: August 1, 2025
• Primary Completion (Estimated): August 1, 2030
• Study Completion (Estimated): August 1, 2030
• Last Updated: April 21, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share