# Project 2 Intrathecal Anti-PD-1 Immunotherapy for Metastatic Melanoma Patients with Leptomeningeal Disease (LMD)

> **NIH NIH P50** · UNIVERSITY OF TX MD ANDERSON CAN CTR · 2021 · $290,680

## Abstract

Project 2: Project Summary/ Abstract 
Antibodies that inhibit PD-1 on the surface of T cells have revolutionized the treatment and outcomes of 
patients with metastatic melanoma. However, metastasis to the central nervous system (CNS) remains a 
common and devastating complication of advanced melanoma, and the CNS is a frequent site of treatment 
failure for current therapies. There are multiple treatment options for melanoma patients with parenchymal 
brain metastases. In contrast, there are very few treatment options for patients that develop leptomeningeal 
disease (LMD). LMD can cause significant neurological deficits, and the median survival for melanoma 
patients with LMD is less than 2 months. Thus, there is a critical unmet need to develop more effective 
treatments for patients with LMD from melanoma. Previous experience with trastuzumab and rituximab in 
breast cancer and lymphoma, respectively, have demonstrated that intrathecal (IT) administration of cancer 
therapies can increase drug levels in the cerebrospinal fluid (CSF) and clinical benefit in patients with LMD. 
Our unique and long-term experience with intrathecal IL2 (IT IL2) has similarly demonstrated that intrathecal 
immunotherapy can achieve durable disease control and survival in a subset of melanoma patients with LMD. 
However, long-term survival with IT IL2 is rare, and treatment-related toxicity with IT IL2 is universal. Thus, 
there remains an unmet need for therapies for LMD that are more active and less toxic. We hypothesize that 
IT administration of anti-PD-1 antibodies will be safe and induce an anti-tumor immune response in the CSF in 
metastatic melanoma patients with LMD. In order to test this hypothesis, in Aim 1 we will conduct a novel 
phase I/Ib study to determine the safety and maximum tolerated dose of combined IT and intravenous (IV) 
administration of the anti-PD-1 antibody nivolumab in metastatic melanoma patients with LMD. This is trial, 
which has recently been approved by the FDA, will be the first to assess the safety of IT anti-PD-1, and it 
represents an important new option for patients with LMD. In Aim 2, CSF and blood collected from patients in 
the trial at multiple timepoints will be analyzed for immune cell subsets and cytokines. The results will be 
analyzed to characterize the effects of IT + IV nivolumab treatment, and to improve our understanding of the 
immune microenvironment of the CSF. In Aim 3, cell-free tumor DNA (ctDNA) isolated CSF and blood will 
undergo next generation sequencing (NGS) to detect and quantify somatic mutations. Results will be used to 
evaluate changes in mutation burden and profile over time, and to compare mutations detected in the CSF to 
those detected in blood and in tumor tissue. Together these studies address an unmet clinical need for new 
treatment options for melanoma patients with LMD, and to improve our understanding of the molecular and 
immune features of this aggressive disease. The results of th...

## Key facts

- **NIH application ID:** 10208809
- **Project number:** 5P50CA221703-03
- **Recipient organization:** UNIVERSITY OF TX MD ANDERSON CAN CTR
- **Principal Investigator:** Jennifer A. Wargo
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $290,680
- **Award type:** 5
- **Project period:** 2020-06-01 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10208809

## Citation

> US National Institutes of Health, RePORTER application 10208809, Project 2 Intrathecal Anti-PD-1 Immunotherapy for Metastatic Melanoma Patients with Leptomeningeal Disease (LMD) (5P50CA221703-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10208809. Licensed CC0.

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