Adoptive T-cell therapy (ACT) with tumor infiltrating lymphocytes (TIL) has proven to be a powerful treatment option for patients with metastatic melanoma 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 induces objective responses in about 50% of melanoma patients with tumors expressing BRAFV600E/K. In addition to the direct anti-cancer effect, vem has been shown to increase T-cell infiltration into tumors, upregulate melanoma antigen expression and increase the frequency of TIL recognizing autologous melanoma cells.
Center for Cancer Immune Therapy (CCIT) has launched a non-randomized phase II study planned to include 12 patients in order to evaluate the feasibility and safety of combining vemurafenib with T-cell therapy. In addition, clinical responses are evaluated according to RECIST criteria and extensive immune monitoring is performed.
Patients will receive vem for one week prior to excision of tumor material for T-cell generation and until admission. During admission patients will receive a preparative high dose lymphodepleting chemotherapy regimen consisting of cyclophosphamide and fludarabine before getting their T-cells reinfused. To support the T-cells, patients are treated with an intermediate dose of interleukin-2 following the decrescendo regimen.
(ClinicalTrials.gov ID NCT02354690)