Chairs: Soma Sengupta, MD, PhD, MBA, and Jan Drappatz, MD

Dr. Sengupta (University of North Carolina, Chapel Hill, professor of neurology and neurosurgery, division chief of adult neuro-oncology) and Dr. Drappatz (University of Pittsburgh Medical Center) are taking over the Medical Neuro-Oncology Subcommittee from Dr. M. Gilbert and Dr. E. Galanis. They would like to acknowledge Dr. Gilbert’s retirement from Neuro-oncology this year and Dr. Galanis’ selection to chair of the Alliance for Clinical Trials in Oncology and their enormous contributions to neuro-oncology. Like their predecessors, Dr. Sengupta and Dr. Drappatz appreciate the opportunity to help foster interdisciplinary activities by promoting educational opportunities and dialogue that focus on areas of interest for neurosurgical and medical neuro-oncologists. There has been an evolution of cellular therapies, focused ultrasound technologies, personalized vaccines for GBMs and many other trials and studies that deserve highlighting.

2024 saw the publication of two CAR-T Phase 1 trials showing promise in the recurrent GBM setting. Dr. S. Bagley’s team published the results from six patients in Nature Medicine on the benefits of intrathecal bivalent CAR T cells targeting EGFR and IL13Rα2 in recurrent glioblastoma (doi: 10.1038/s41591-024-02893-z). In addition, Dr. Maus’ team published data from three participants in Intraventricular CARv3-TEAM-E T cells which target the epidermal growth factor receptor [EGFR] variant III [EGFRvIII] tumor-specific antigen and the wild-type EGFR protein in recurrent glioblastoma in the New England Journal of Medicine (DOI: 10.1056/NEJMoa23143). These trials utilizing bivalent CAR-T trials seek to overcome tumor heterogeneity and antigen escape observed in earlier CAR-T cell studies. The trials are ongoing with a plan to expand to newly diagnosed GBM patients.

Dr. A. Sonabend and colleagues published an elegant study looking at low-frequency pulsed ultrasound in aiding the delivery of doxorubicin in gliomas. The study showed for the first time that a skull-implantable ultrasound device can enhance the penetration of doxorubicin and immune checkpoint blockade antibodies into the human brain. A planned clinical trial will test safety and effectiveness in prolonging survival in recurrent GBM. We believe that MRI-guided focused ultrasound holds promise as a versatile tool for improving drug delivery and favorably altering the tumor microenvironment.

On the personalized vaccine front, Dr. Biskup and colleagues recently described 173 GBM patients treated with a personalized neoantigen-derived peptide vaccine, immunogenicity of this personalized peptide vaccine approach as well as clinical efficacy relative to historical, propensity-matched controls. Furthermore, the vaccine was able to elicit robust T-cell responses in a high proportion of patients, which correlated with survival ( Latzer, P., Zelba, H., Battke, F. et al. Nat Commun 15, 6870 (2024).

We would like to highlight two ongoing GBM clinical trials. Earlier this year, based on the existing phase 1b data of IGV-001, an anti-sense oligonucleotide vaccine, the FDA fast-tracked it for the treatment of newly diagnosed GBMs. Following surgical resection, patients in the ongoing phase IIb trial’s IGV-001 arm received biodiffusion chambers implanted with a mix of personalized whole tumor-derived cells and an antisense oligonucleotide (IMV-001). The trial completed accrual in May 2024. Another registration trial, the phase II b SURVIVE study evaluating SurvaxM, an amino acid-peptide-conjugate vaccine in newly diagnosed GBM has also completed accrual within the past year. The results of both studies are expected within the next year.

ASCO had several oral presentations of importance. For brain metastasis, Novocure’s METIS (EF-25) phase 3 trial showed that the Optune device for non-small cell lung cancer prevented intracranial progression, but it is not yet clear if the intervention improved overall survival (MP Mehta, V Gondi, MS Ahluwalia, et al, ASCO abstract 2008).

In a multicenter trial in anaplastic oligodendroglioma, TMZ/RT was compared with PCV/RT, suggesting an improved overall survival with PCV/RT compared with TMZ/RT, albeit at increased toxicity ( SEO Kacimi, C Dehais, L Feuvret, et al. ASCO abstract 2004). Dr. Sanai and colleagues demonstrated adequate (therapeutic) brain penetrance of niraparib which has led to initiation of a randomized phase III trial in GBM (Niraparib efficacy in patients with newly diagnosed glioblastoma: Clinical readout of a phase 0/2 “trigger” trial. N Sanai, Y Umemura, T Margaryan, et al. ASCO abstract 2002). Finally, Dr. Brastianos presented the results of a phase II trial of abemaciclib in patients with grade 2/3 meningiomas harboring somatic NF2 or CDK pathway alterations. The trial met its primary endpoint of improving PFS6 (ASCO abstract 2001, PA Kaliopi Brastianos, K Dooley, SM Geyer, et al).

The National Brain Tumor Society has provided a valuable resource for additional trial information on other tumor types and pediatric brain tumors.

Lastly, the American Brain Tumor Association is holding its annual highly-attended patient and caregiver meeting. The focus will be on brain tumor patient survivorship, highlighting the need for cancer survivorship, neuro-palliative care and integrative oncology to improve patients’ quality of life.