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Melanoma, melanoma, multiple cancer, breast cancer, toxicity, lymphoma
MELANOMA, MELANOMA, MULTIPLE CANCER, BREAST CANCER, SOLID TUMORS, LYMPHOMA
Melanoma has the highest propensity among all common solid tumors for the development of central nervous system (CNS) metastasesThere is a clear unmet need for new, more effective treatments for melanoma patients with LMD. The current therapeutic options for melanoma LMD patients consist of radiation, systemically administered therapies or a limited number of IT therapiesOwing to the poor penetration of many agents into the cerebrospinal fluid (CSF), IT administration of anti-cancer agents has been explored in patients with LMD in multiple cancer types. IT administration of trastuzumab in breast cancer and of rituximab in lymphoma patients demonstrated that such approaches achieve significant drug exposure in the CSF and clinical benefit in patients with LMD, thus frequently being used in this setting, although randomized trials are still needed to definitively assess the efficacy of this approachBased on the improved efficacy and safety of systemically administered anti-PD1 compared with IL-2, we hypothesized that the treatment of patients with melanoma LMD with IT anti-PD1 would be safe and feasible. We first evaluated the toxicity of IT administration of anti-PD1 antibody in an immunocompetent mouse model. We then designed a first-in-human dose-finding study using concurrent administration of IT and IV anti-PD1. Here, we report a nonprespecified interim analysis detailing the dose escalation portion, recommended IT dose, safety profile and preliminary signal for efficacy of concurrent IT and IV nivolumab in melanoma patients with LMD.