Melanoma brain metastases (MBM) are a leading cause of morbidity and mortality for patients with advanced disease. Modern systemic therapies do not adequately control brain metastases. For patients whose disease has progressed on standard immunotherapy and targeted therapy (if appropriate), there are no approved treatments that have demonstrated efficacy against MBM. Little is known about the mechanisms of MBM growth or treatment resistance. Few new treatment approaches are on the horizon, as patients with MBM are frequently excluded from clinical trials.

A new type of immunotherapy using tumor infiltrating lymphocytes (TIL) has demonstrated efficacy in advanced melanoma. Lifileucel, an drug made from patients’ own T cells, was recently shown to be safe and effective in patients with melanoma that has progressed on standard immunotherapy and targeted therapy. These promising preliminary results have been met with great enthusiasm for TIL therapy as a potential approach for melanoma that has progressed after immunotherapy treatment. Follow-up studies are ongoing with expectation of FDA approval within the next year. Participants with active MBM were excluded from lifileucel trials to date, so the feasibility and safety of lifileucel are unknown in this population. Only a small number of patients with active MBM have been treated with any type of TIL therapy. To address the critical need for therapeutic options and deeper biological understanding of MBM, we propose a pilot study to rigorously define the feasibility of treating patients with MBM with lifileucel.

This will be the first study to evaluate lifileucel for active MBM. Establishing feasibility and safety of this approach could rapidly lead to larger phase II efficacy and combination trials, which have the potential to change treatment paradigms and improve outcomes from this dreaded complication of melanoma. We have proposed extensive correlative analyses using blood and cerebrospinal fluid (CSF) to enhance our mechanistic understanding of the biology driving the growth and treatment resistance of brain metastases and what changes occur during the course of cell therapy treatment.

Treatment of MBM, particularly after progression on standard immunotherapy treatments, is one of the most urgent unmet needs in the therapy of melanoma. Successful completion of this trial and the correlative studies could improve clinical management of this morbid complication of melanoma and inform decision-making for further cellular therapy approaches in MBM and other cancers that metastasize to the brain.