At the 2026 American Society of Clinical Oncology (ASCO) annual congress, oral abstract presenters highlighted new and exciting central nervous system (CNS) tumour treatments. CNS tumours, including gliomas and glioblastomas (GBMs), represent some of the most challenging conditions in oncology due to their complexity, limited treatment options, and low survival rate. However, a new wave of clinical and translational research is beginning to broaden the treatment landscape, many of which were covered at the ASCO 2026 annual meeting, with early signals of benefit across targeted agents, cell therapies, and gene-based approaches.
Notably, the clinical trials MAGMA and JCOG1703 further demonstrated that some treatment regimens for newly diagnosed GBMs (ndGBMs), namely extending temozolomide cycles, neoadjuvant temozolomide prior to chemotherapy, and carmustine wafer implantation, do not improve overall survival (OS) or progression-free survival (PFS) when compared to the standard of care (SOC). These results further demonstrate the lack of viable treatment options for patients with GBMs, as most cases of ndGBM will recur.
ASCO 2026 also highlighted interesting and innovative therapeutics for GBM such as a Phase I trial in ndGBM, which combined a personalised neoantigen peptide vaccine, NeoVax, and Keytruda (pembrolizumab). Importantly, the median overall survival (OS) reached an astounding 36.9 months in MGMT-methylated patients and 19.0 months in unmethylated patients, against propensity-matched historical controls of 25.3 and 16.7 months. Neoantigen-specific T-cell responses appeared in 65% of patients ex vivo and 97% in vitro; ex vivo responders survived markedly longer. NeoVax’s Phase I results showed that personalised cancer vaccines are a promising modality for immune modulation, especially in “warming” cold tumour microenvironments.
In parallel, the application of CAR T-cell therapy in EGFR-amplified recurrent GBM (rGBM) is emerging as a meaningful advance. In a Phase I study, bivalent CAR T cells targeting EGFR and IL13Rα2 produced an encouraging median OS of 12 months without evidence of long-term or delayed toxicities. While some patients experienced an initial decline in neurological function following infusion, patients recovered to baseline by one month after CAR T-cell infusion. Additionally, the presentation highlighted a long-term responder, of 33 months, who developed rapid progression with leptomeningeal disease (LMD) between pre-CART surgery and receiving CAR T cells. This patient had CAR T cells detectable in cerebral spinal fluid and blood at the 24-month timepoint. Dr Stephen Bagley highlighted that this patient’s long-term response could be due to the LMD, but this needs to be studied more. The complexity of GBM also lies in its heterogeneity, and as there are not many trials targeting specific biomarkers in GBM, this bivalent CAR T-cell therapy not only demonstrates the need for precision medicine in GBM but also the effectiveness of those treatments.
Voranigo (vorasidenib) is a dual mIDH1/2 inhibitor that demonstrated major long-term efficacy, with a median PFS of 44.1 months for grade 2 mutant gliomas, in the INDIGO Trial. Voranigo is now marketed in over 40 countries. If Voranigo is shown to be effective in high-grade IDH mutant gliomas as well, it would represent an effective new treatment option for these aggressive cancers.
Gene therapy is also gaining traction, particularly through approaches aimed at reprogramming tumour biology rather than solely targeting proliferation. A pioneering study of the AAV6 NeuroD1 trans-differentiation therapy, a first-in-human viral vector, in recurrent malignant gliomas, demonstrated favourable safety and efficacy signals. A disease control rate of 54.5% was achieved by reprogramming tumour cells into non-proliferative, neuron-like cells. This trial, based in China, emphasises the potential for gene-based modalities to open new therapeutic pathways in tumours that have traditionally been resistant to standard intervention.
Despite these developments, CNS tumour treatment remains structurally challenging. The blood–brain barrier (BBB) continues to be one of the largest challenges to overcome; therefore, there is excitement over treatments that can bypass the BBB using devices such as tumour-treating fields (such as Optune) and implantable devices such as SonoCloud. Additionally, two oral presentations highlighted implanting tile-based radiation post-resection, including cesium-131, which may pose issues for patients looking to enrol in other clinical trials. Another major barrier is tumour heterogeneity and the complex CNS tumour microenvironment, which reduces the consistency and durability of drug responses. The progression and multiple resistance mechanisms further reinforce the need for innovative, multi-pronged approaches and combination strategies that address both tumour-intrinsic and immune-mediated factors.
Overall, although CNS tumours have long been associated with limited options and poor prognosis, the latest clinical evidence points to a more dynamic and diversified pipeline. Continued research and well-designed clinical trials will be essential to validate these early findings, refine safety profiles, and ultimately deliver more effective, personalised treatment strategies for patients.
