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.
Lynparza shows potential as first line of care for GBM
Data from the Phase IIa OLA-TMZ-RTE-01 trial was presented in the central nervous system tumour oral session.
GBM remains one of the most difficult cancers to treat, and progress has been incremental despite decades of effort. One strategy is the use of poly-ADP ribose polymerase (PARP) inhibitors that may enhance the effect of radiation and alkylating chemotherapy like Lynparza (olaparib), targeting PARP1 and PARP2. This is because PARP enzymes are involved in DNA damage repair and by blocking this pathway, it may increase sensitivity to DNA-damaging treatments such as radiotherapy and temozolomide. Additionally, PARP1 is highly expressed in GBM. The OLA‑TMZ‑RTE‑01 study was designed to evaluate the safety and potential activity of adding olaparib to standard radiotherapy + temozolomide in patients with unresectable or partially resectable glioblastoma as the first line of treatment, regardless of O-6-methylguanine-DNA methyltransferase (MGMT )promoter methylation.
Phase I results have been released for the safety of the regimen and found that intermittent dosing of olaparib at radiosensitizing concentrations concomitant with the Stupp protocol was safe for patients with unresectable GBM. Phase IIa results presented at ASCO 2026 demonstrated that the median overall survival was 17.2 months and the 12-month rate is 69.1%. Additionally, results showed that the OS compares favourably to Stupp biopsy-only (14.9 vs. 9.4 months) and partial-resection (19 vs. 13.5 months) historical data, where gross total resections were included. These results are promising as this population, unresectable or partially resectable GBM, is a great unmet need in GBM as the Stupp protocol’s efficacy is limited due to the large tumour burden; therefore, incorporating a multi-faceted treatment approach including PARP inhibitors like olaparib would be beneficial to this patient population.
A major limitation in the data was a lack of a control arm; instead researchers used previous studies by Stupp, the original Stupp protocol published in 2005, and EF-14, which is the original 2005 protocol with TTFields included. These previous studies, as mentioned earlier, have 35–53% of their patients undergo gross total resection, compared to this study where it was 0%. Therefore, the data presented supports the rationale for a randomised Phase III trial to confirm the benefit of PARP inhibition in this patient setting; however, including a strong control arm would greatly support future trial results.
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.
Keytruda combinations in GBM
The most recent clinical and translational data suggest that Keytruda may function better as a combination therapy in GBM rather than a monotherapy. With a Phase III trial, NCT06556563, investor attention is increasingly shifting to whether a rationally designed regimen can translate biologic synergy into a durable clinical benefit.
Phase II trial results for tumour treating fields (TTFields), Keytruda, and temozolomide in newly diagnosed GBM (ndGBM) were released in 2025 (Chen et al., 2025). This study is notable as the regimen creates immune priming upstream so immune checkpoint inhibitors like Keytruda are more effective. The Phase II trial combined the use of TTFields, Optune Gio, to promote clonal T-cell expansion via a type I interferon pathway, and Keytruda, which supports the adaptive replacement of these clones, sustaining T-cell activation and memory formation.
At ASCO 2026, a poster was presented on the Phase III EF-41/KEYNOTE 58 trial with a study status. As of April 2026, recruitment has started at more than 80 sites globally, and the company is hoping to start the trial soon. GlobalData forecasts pembrolizumab’s sales to be $31.1bn in 2026 and to drop to $8.1bn by 2032 due to patent expirations.
SurVaxM is a peptide vaccine-targeting survivin, a protein highly expressed in GBM and implicated in tumour survival and immune evasion. The Phase IIa single-arm clinical trial showed SurVaxM to be safe and capable of triggering antibody production and CD8+ T-cell activity across patient subgroups despite MGMT-methylation status (Rosewell Park Comprehensive Cancer Center, 2022). Additionally, based on earlier Phase IIa findings, 93.7% of participants treated with SurVaxM and standard of care were alive one year after diagnosis, which is higher than the historical one-year survival of 25–30%. The company’s poster on the topic at ASCO 2026 did not include interim results from the company’s Phase IIa or Phase IIb findings. The assumed one-year survival presented on the poster was 75% for SurVaxM when compared to the placebo (60%). The trial’s initial primary completion date was set for 2024, and little interim data has been released since.
