T cell therapy in combination with Vemurafenib in BRAF mutated metastatic melanoma patients

Background Adoptive T cell therapy (ACT) with tumor infiltrating lymphocytes (TIL) has proven to be a powerful treatment option for patients with metastatic melanoma, even when heavily pretreated, with response rates of approximately 50% and durable complete responses in about 15%. However, there is still a need for improving TIL efficacy and a promising strategy is combination with immunomodulating agents. One such is Vemurafenib (Vem), a selective BRAF inhibitor, which has been shown to induce objective responses in about 50% of treated melanoma patients expressing BRAF, improving progression-free survival and overall survival compared to standard chemotherapy. In addition to the direct anti-cancer effect, Vem has been shown to increase T cell infiltration into tumors, up-regulate melanoma antigen expression and increase the frequency of TIL recognizing autologous melanoma cells. Combining TIL treatment and Vem is currently being investigated in other clinical trials testing different treatment schedules (ClinicalTrials.gov Identifier: NCT01659151 and NCT01585415).