New Immunotherapy Trial for Recurrent Meningioma
Led by the UCSF Brain Tumor Center, a new clinical trial for recurrent meningioma is now open for enrollment. The phase 2 clinical trial will evaluate pembrolizumab – an immunotherapy drug – in combination with radiation to treat recurrent meningioma (grades I-III).
While various immunotherapies work through different mechanisms, they are all designed to enhance the immune system’s ability to recognize and target cancer cells. Pembrolizumab does so by binding and inhibiting PD-1, a protein that normally protects the body from attacking itself. Specifically, PD-1 works by detecting a molecular signal, called PD-L1, which is made by various cells throughout the body. Certain cancer cells produce PD-L1 themselves, and take advantage of the body’s natural protection mechanism. Blocking PD-1 with pembrolizumab allows the immune system to better recognize and attack the tumor.
“We feel that this is a very promising strategy, because higher grade meningioma have more PD-L1 and PD-1 expression,” said UCSF neuro-oncologist Nancy Ann Oberheim Bush, MD, PhD.
Meningioma may be further amenable to immunotherapies in general, as they are typically located near the sinuses, where lymphatic drainage occurs – a major source for circulating lymphocytes and other immune cells. Indeed, immune cells have been observed to infiltrate meningioma.
While pembrolizumab has had excellent results in patients with other cancers, including melanoma and metastatic non-small cell lung cancer, it is still under investigation for primary brain tumors, particularly in combination with other therapies. This trial will study the effect of pembrolizumab in combination with stereotactic radiosurgery, which delivers a high dose of radiation to the precise location of the tumor.
“Combining the therapy with radiation may be very beneficial,” said Bush, “because radiation itself increases immune activation.” By killing tumor cells, radiation also causes the release of tumor-specific proteins or molecules which further help mobilize the immune system against the tumor.
Bush is the principal investigator for the study, together with UCSF radiation oncologist Steve Braunstein, MD. The phase 2 clinical trial, which will enroll 90 patients at UCSF, is one of the few studies currently available across the nation for meningioma.
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