REGO combined with BRAF-/MEK-inhibitors in advanced pretreated BRAFV600-mutant melanoma (RegoMel)

Dr Iris Dirven presented the results of a clinical trial conducted as part of her doctoral research, evaluating a therapeutic strategy for patients with BRAF-mutant melanoma who developed disease progression on standard BRAF–MEK inhibition. The rationale for the study stems from preclinical evidence showing that regorafenib, a RAF-dimer inhibitor, can partially reverse resistance mechanisms that emerge under BRAF–MEK inhibitor therapy.

The trial enrolled 18 patients, all of whom had progressed on prior BRAF–MEK inhibition. At the point of progression, regorafenib was added to the existing targeted therapy. The median time on treatment was 10 weeks. In the response-evaluable population, the overall response rate was 14%, and the disease control rate was approximately 40%. Notably, 12 of the 18 participants had active brain metastases at enrollment, representing a particularly challenging clinical subgroup with historically limited therapeutic responsiveness.

Despite the overall modest efficacy, a subset of patients experienced clinically meaningful benefit. Four patients—including three with brain metastases—remained on treatment for more than six months. Radiological responses were observed within the central nervous system: one patient achieved a partial intracranial response, and another achieved a complete intracranial response.

Although the study did not meet its primary endpoint, these findings indicate that a proportion of patients may derive sustained benefit from the addition of regorafenib to BRAF–MEK inhibition after progression. Ongoing translational analyses aim to identify the resistance mechanisms and molecular characteristics that could predict sensitivity to this triple-combination approach, with the goal of refining patient selection in future studies.