ESMO 2026 | Phase I trial of intrathecal cDC1s in breast cancer leptomeningeal disease
Peter Forsyth, MD, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, discusses a Phase 1 trial (NCT05809752) of intrathecal peptide-pulsed dendritic cells (cDC1s) for leptomeningeal disease in patients with breast cancer. A promising median survival was reported, and predictors in the cerebrospinal fluid can help identify who will respond to the treatment. This interview took place at the European Society for Medical Oncology (ESMO) 2026 Congress in Madrid, Spain.
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Transcript
So just a word of background, leptomeningeal disease is a complication of systemic cancer where the tumor cells go to the covering of your brain and spinal cord. It’s usually rapidly fatal, like over two or three months. It’s kind of a nasty thing to have. Many breast cancer patients get this, and most of them are pretty young for reasons we don’t completely understand...
So just a word of background, leptomeningeal disease is a complication of systemic cancer where the tumor cells go to the covering of your brain and spinal cord. It’s usually rapidly fatal, like over two or three months. It’s kind of a nasty thing to have. Many breast cancer patients get this, and most of them are pretty young for reasons we don’t completely understand. So it’s regarded as an incurable thing so we raise these dendritic cells against proteins that are present in the tumor cells so you can kind of educate your body to recognize and fight the tumor. So I say the dendritic cells are like Paul Revere in the American Revolution, where it helps identify foreign things that need to be killed. So we administer them intrathecally in this Ommaya Reservoir, like a port. And the results are pretty interesting. First of all, everybody got a headache. We treated 15 patients, and the median survival was about 18 months, which is pretty good. We’d like it to be a lot longer. But there’s several patients that clearly benefited and had very long survivals. Of course, there’s some that had short survivals. So I think it’s just very promising. We’re trying to figure out now. And we do have predictors when we look at the CSF where we can predict who’s going to respond and who isn’t going to respond. So it’s super important. So we think it’s promising and early. So the next steps that we’re doing to look into this more is to finish all the lab work because it’s easy to figure this stuff out. It just takes time. You just need to know some molecular biology. And so we’ve already opened a phase two follow-on study. So we need to finish looking at all the data from this study. But in the meantime, we started the next study. Because these patients are pretty desperate. There’s very few clinical trials for LMD. So we really work hard to try to get trials for the patients out there so that they can benefit.
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