1082O Concurrent intrathecal (IT) and intravenous (IV) nivolumab (N) for melanoma (MM) patients (pts) with leptomeningeal disease (LMD)

Pts with LMD have dismal prognosis and few clinical trial options. We previously reported safety and efficacy of the dose escalation (DE) phase of an open label, single arm, single center phase I/IB trial (NCT03025256) for MM pts with LMD. Concurrent IT/IV N was well tolerated, no new or unexpected CNS toxicities. 50mg IT N was the recommended dose (RD) for expansion accrual. Here we report the updated safety and efficacy results for the escalation and expansion cohorts. Study design methods were previously reported (Glitza, Nat Med, 2023). Primary objectives were to determine safety and RD of IT/IV N and safety in RD expansion cohort. Secondary objectives included overall survival (OS). Fifty pts total were treated (48 pts with MM, 2 pts with NSCLC), including 31 pts with IT N 50 mg. Median age at LMD diagnosis was 49 (19-74); 27 pts are male. All pts had radiographic evidence of LMD; 26 pts had positive CSF cytology at baseline. Median follow-up and OS is shown in the table. Safety profile remained consistent with prior reports: 9 pts (18%) experienced gr 3 AEs, none had gr 4 or 5. Nausea (46%), rash (40%), vomiting (34%), diarrhea (20%), and dizziness (20%) were the most common AEs. Thirty pts (60%) experienced AEs after IT N administration, including 2 gr 3 (vasogenic edema, elevated ALT); remainder were gr 1/2.Table: 1082OMed follow up wks (range)Median OS Wks (95% CI)OS 13 wksOS 26 wksOS 52 wksAll27.3 (2, 251)30 (19, 64)68%54%35%<50 mg25 (5, 251)25 (15, 143)68%47%26%50 mg30 (2, 140)41 (13, 65)68%58%43% Open table in a new tab This updated analysis confirms the safety of IT (50mg)/IV N. There were no significant differences in OS between the tx groups and no unexpected toxicities were observed at RD. These results support further evaluation of IT immunotherapy strategies for pts with LMD. Insights gained from translational studies on CSF samples will aid in the development of future IT immunotherapy strategies for these patients.