A pair of multicenter clinical trials at NYU Langone targeting two vastly different types of brain tumors—glioblastoma and meningioma—are offering patients with these conditions opportunities for access to novel treatments.

Pirimidone ONC201 Looks Promising to Eliminate Rare Subtype of Glioblastoma

Glioblastomas, the most common malignant intracranial brain tumors, are highly aggressive cancers with limited treatment options. At NYU Langone’s Perlmutter Cancer Center, a phase 2 trial is evaluating the investigational drug ONC201, which targets the small subset of glioblastoma patients who have failed chemotherapy and whose tumors have a histone H3 K27M mutation. These mutations, which comprise only a few percent of glioblastomas, occur in young adults, typically people in their 20s through 40s, and appear in midline structures within the central nervous system.

While the exact mechanism of action of ONC201 is controversially discussed, prior studies and case reports have demonstrated promising results of ONC201 in the rare subset of glioblastomas characterized by the H3 K27M mutation. This has resulted in the launch of this phase 2 clinical trial, spearheaded by researchers at NYU Langone. The clinical trial exclusively enrolls patients with H3 K27M mutant glioblastomas. Importantly, the trial is open to patients with brainstem and spinal cord tumors, a patient population that is typically excluded from other glioblastoma studies.

Since the trial opened in 2017, NYU Langone has enrolled 17 patients from all over the world—the most of any of the centers conducting the trial. Two patients have had partial responses, and one patient had a near-complete response, which has been sustained for nearly two years since beginning this drug.

“For glioblastoma patients, there are very few promising actionable targets that are currently being explored in clinical trials,” says Sylvia C. Kurz, MD, PhD, principal investigator and assistant professor in the Departments of Medicine and Neurology. “In general, the natural history of these tumors is that once they have failed radiation and traditional chemotherapy, there’s usually nothing that stops their growth.”

An Antibody Fused to a Radionuclide Targets Meningioma Tumors

Meningiomas are the most common benign intracranial tumors; nevertheless, about 10 to 15 percent of cases demonstrate aggressive clinical behavior. In July 2019, a phase 2 clinical trial opened at Perlmutter Cancer Center for patients with intracranial meningiomas that are unresectable, have progressed despite prior therapies, or both. The trial uses a radionuclide-linked antibody, 177Lutetium-DOTATATE, or Lutathera®, that targets somatostatin receptor type 2, which is expressed in approximately 95 percent of all meningiomas.

Perlmutter Cancer Center is the first U.S. site for what will be a multicenter study led by its investigators. Later this year and next, the University of Pittsburgh Medical Center, Cleveland Clinic, and Weill Cornell Medical Center are expected to begin enrolling participants. Dr. Kurz is co-chair investigator with Elcin Zan, MD, assistant professor in the Department of Radiology. Erik P. Sulman, MD, PhD, professor and vice chair for research in the Department of Radiation Oncology and co-director of the Brain and Spine Tumor Center, is overall principal investigator.

As part of the study, 68Ga-DOTATATE PET MRI is being used as a potential biomarker of how strongly somatostatin receptor type 2 is expressed and thus will identify patients who might benefit from Lutathera®. 177Lutetium-DOTATATE binds to somatostatin receptors on meningioma cells. Once the antibody is bound to the receptors, it is taken into the cell, and the bound radioisotope delivers a lethal dose of short-wavelength radiation.

Lutathera® was approved by the U.S. Food and Drug Administration in early 2018 for treatment of advanced neuroendocrine tumors. Based on the results of the clinical studies that have been performed with neuroendocrine tumors, Dr. Kurz says there is reason to believe that this treatment is safe and might offer benefit to meningioma patients.

The Lutathera® trial has generated interest from patients around the country, as well from investigators interested in opening subsites of the trial at their institutions.

“For patients with progressive meningiomas, there are no established medical treatment options available that have been demonstrated to be effective,” says Dr. Kurz. “Because there is only a limited number of clinical trials available, this is a great opportunity to offer a clinical trial to this patient population.”