Central Nervous System
If it’s your first time on this website, please read the disclaimer section.
Jul 06 – Jul 13, 2026
Anti-LAG-3 with or without anti-PD-1 in recurrent glioblastoma: a phase 1 trial.
NAT MED · Q1 JOURNAL - RANK #1/195TOP-TIER
This phase 1, open-label, multicenter trial evaluated the safety and preliminary activity of the anti-LAG-3 antibody relatlimab alone or combined with the anti-PD-1 antibody nivolumab in 46 patients with recurrent glioblastoma. Neoadjuvant administration stimulated intratumoral CD8 T cell infiltration, and 12-month overall survival rates reached 34.8% for relatlimab alone and 52.2% for combination therapy. Treatment-related grade 3-4 adverse events occurred in six patients on combination therapy, and no such events occurred with monotherapy. Overall, these results demonstrated an acceptable safety profile and suggest potential clinical benefit requiring further investigation.
10.1038/s41591-026-04475-7
Jun 29 – Jul 06, 2026
Personalized neoantigen-pulsed autologous dendritic cells in newly-diagnosed glioblastoma: a phase Ib trial.
NAT COMMUN · Q1 JOURNAL - RANK #10/135TOP-TIER
In this single-arm, open-label phase Ib clinical trial, investigators evaluated the safety and preliminary efficacy of a personalized neoantigen-pulsed autologous dendritic cell vaccine (ZSNeo-DC) in patients with newly-diagnosed glioblastoma. Eleven patients were enrolled and received intradermal ZSNeo-DC following surgery and standard radio-chemotherapy, with safety measured by adverse event incidence and severity. Treatment was well tolerated, with primarily grade 1/2 AEs, a median PFS of 16.2 months, a 12-month OS rate of 100%, and a significant rise in immune responses post-vaccination. These promising results support further clinical evaluation of ZSNeo-DC in expanded phase II trials.
10.1038/s41467-026-75066-w
DNA, Peptide Vaccines Advance Against GBM.
CANCER DISCOV · Q1 JOURNAL - RANK #10/326TOP-TIER
The primary objective was to evaluate the safety and immunogenicity of two personalized vaccine approaches, GNOS-PV01 and NeoVax, in patients with glioblastoma. This Phase I trial included adult patients receiving a DNA-based or peptide-based vaccine designed to elicit an immune response against tumor-specific antigens. Both vaccines were found to be effective, particularly GNOS-PV01 for MGMT-unmethylated glioblastoma. Overall, these first-in-human results indicate that individualized vaccine administration holds promise as an immunotherapeutic strategy against treatment-refractory glioblastoma.
10.1158/2159-8290.CD-NW2026-0075
Temozolomide Versus Radiotherapy as First-Line Therapy for Low-Grade Glioma: Mature Results of a Randomized Phase III Trial (EORTC 22033-26033/NCIC-CTG/TROG/MRC-CTU).
J CLIN ONCOL · Q1 JOURNAL - RANK #6/326TOP-TIER
This randomized Phase III clinical trial compared temozolomide (TMZ) and radiotherapy (RT) as first-line treatments for patients with high-risk low-grade gliomas (WHO grade 2). Among 478 participants, median overall survival (OS) was similar between arms for astrocytoma, IDHmt/1p/19q noncodeleted (6.6-6.7 years) and oligodendroglioma, IDHmt/1p/19q codeleted (12.9 years for RT vs. 14.9 years for TMZ). TMZ demonstrated better OS for IDH non-mutant tumors (4.7 vs. 2.5 years, HR 0.47, p = 0.0068). While TMZ and RT showed no OS or progression-free survival differences across molecular subtypes, researchers noted the need for molecular-based personalized treatment strategies and challenged the use of age as a prognostic cutoff.
10.1200/JCO-25-02735
IDH1-mutant vaccine in newly diagnosed astrocytoma: final analysis of the multicenter, single-arm, open-label, first-in-human phase 1 NOA16 trial.
NAT CANCER · Q1 JOURNAL - RANK #11/326TOP-TIER
The NOA16 trial evaluated the safety and immunogenicity of an IDH1-R132H peptide vaccine (IDH1-vac) in 33 newly diagnosed grade III and IV IDH1-R132H astrocytoma patients, integrated into standard care. The study reported 8-year progression-free and overall survival rates of 0.42 months (CI: 0.24-0.59) and 0.66 months (CI: 0.46-0.79), respectively, with median overall survival for grade IV patients reaching 106.1 months (CI: 39.6-NE). Sustained antibody responses were linked to favorable outcomes, and T cell responses were detected in cases of pseudoprogression. The results support further investigation of IDH1-vac in a randomized phase 2 trial for IDH-mutant astrocytomas.
10.1038/s43018-026-01199-y
Multi-antigen-targeting T cells in pediatric central nervous system tumors: a phase 1 trial.
NAT MED · Q1 JOURNAL - RANK #1/195TOP-TIER
This open-label, phase 1 adaptive dose-finding trial (ReMIND) evaluated autologous, systemically administered, trivalent T cells targeting WT1, PRAME, and survivin in children with CNS tumors, including newly diagnosed DIPG without lymphodepletion (arm A) and relapsed/recurrent nonbrainstem tumors without (arm B) or with lymphodepletion (arm C). Sixteen, 28, and 7 patients were enrolled in arms A, B, and C (11, 18, and 4 infused), respectively; treatment was generally well tolerated with fatigue and headache common, two possibly related serious tumor-swelling events, and one grade 5 dose-limiting toxicity in a DIPG patient with hydrocephalus and edema. Dose level 3 (8 × 10 cells per m per dose) was the maximum tolerated dose. Median OS for arm A was 13.7 months (6.2–32.0); median PFS for arms B/C was 5.0 months (0.5–51.6), with three patients disease-free at 31.8, 41.2, and 51.6 months including one complete response.
10.1038/s41591-026-04449-9
Pediatric Brain Tumor Consortium phase 1 study of CD40 agonist sotigalimab in pediatric and young adult patients with recurrent CNS tumors and newly-diagnosed DIPG.
CLIN CANCER RES · Q1 JOURNAL - RANK #29/326TOP-TIER
This prospective phase 1 clinical trial, PBTC-051, evaluated the safety, pharmacokinetics, immune pharmacodynamics, and preliminary efficacy of the CD40 agonist sotigalimab in 31 pediatric and young adult patients with recurrent/progressive CNS tumors and newly-diagnosed post-radiation pre-progression DIPG. Using a 3+3 dose-escalation design, the study identified 0.6 mg/kg every 3 weeks as the recommended phase 2 dose for stratum 1 and 0.3 mg/kg every 3 weeks as the maximum tolerated dose for stratum 2. No objective responses were observed, but 6-month PFS rates were 13.3% (SE 8.1%) for stratum 1 and 31.2% (SE 14.8%) for stratum 2, with well-tolerated safety. Enrichment of immune signaling pathways correlated with higher PFS, and more than 40% of patients developed anti-drug antibodies.
10.1158/1078-0432.CCR-26-0655
Dose escalation with intraoperative radiotherapy in newly diagnosed glioblastoma (INTRAGO-II): an open-label, multicentre, randomised, controlled, phase 3 trial.
LANCET ONCOL · Q1 JOURNAL - RANK #8/326TOP-TIER
This study aimed to evaluate whether intraoperative radiotherapy (30 Gy) in combination with standard care improves outcomes in newly diagnosed glioblastoma compared to standard care alone. Patients aged 18–80 from seven countries were randomly assigned (1:1) to intraoperative kilovoltage radiotherapy plus standard care or to standard care alone in this multicentre, open-label, phase 3 trial (NCT02685605). At a median follow-up of 17.2 months, progression-free survival was 11.0 months in the intraoperative group versus 11.4 months in the control group (HR 1.1, p=0.47), with local recurrence noted as the main progression pattern (72% intraoperative group vs. 71% control group). The study concluded that intraoperative radiotherapy does not enhance outcomes, but it increases serious adverse events (65% intraoperative vs. 53% control), including a higher incidence of radiation necrosis (7% vs. 2%, p=0.06).
10.1016/S1470-2045(26)00235-4
Jun 22 – Jun 29, 2026
A phase 1 trial of iron metabolism-targeting oral gallium maltolate in recurrent and refractory glioblastoma.
NEURO-ONCOL ADV · Q1 JOURNAL - RANK #50/285
This Phase 1 trial evaluated the safety, recommended Phase 2 dose (RP2D), and tumor response signals of oral gallium maltolate in 24 patients with recurrent glioblastoma (GBM) using a 3 + 3 dose-escalation design (500-2,500 mg daily). Grade 1 or 2 adverse effects included diarrhea, anorexia, nausea, and fatigue; the RP2D was 2,000 mg/day based on toxicity and serum gallium levels. Tumor progression occurred in 11 of 22 evaluable patients after 2 cycles, with median overall survival of 16 months and one patient remaining on treatment after 33 cycles. The study concluded that gallium maltolate is safe and warrants further efficacy investigation.
10.1093/noajnl/vdag154
Phase 2 study of regorafenib in patients with progressive glioblastoma after failure of bevacizumab.
NEURO-ONCOL ADV · Q1 JOURNAL - RANK #50/285
This phase 2 study assessed regorafenib monotherapy in 13 patients with progressive glioblastoma refractory to bevacizumab, with a target dose of 160 mg daily on a 3-weeks-on/1-week-off schedule. They underwent MRI every 8 weeks per modified RANO criteria, and 12 of 13 showed progressive disease, leading to early study termination due to futility. The median OS was 4.1 months (95% CI 2.0-7.3), OS at 12 months was 23% (0.2-46), and median PFS was 1.0 month (0.4-1.8), with PFS at 3 and 6 months of 7.7%. A total of 14 Grade 3 or 4 adverse events were observed, indicating suboptimal tolerability and no improvement in survival.
10.1093/noajnl/vdag144
Jun 15 – Jun 22, 2026
The critical role of the endogenous immune compartment after CAR T cell therapy in recurrent GBM.
CELL · Q1 JOURNAL - RANK #3/319TOP-TIER
This study investigates the role of the endogenous immune compartment following CAR T cell therapy in patients with recurrent glioblastoma (GBM). Conducted as a phase 1 clinical trial (NCT05168423), intracerebroventricular bivalent CAR T cells were administered, and immune dynamics in cerebrospinal fluid and tumor samples were longitudinally analyzed across responders and non-responders. The results showed divergent immune responses, with cytotoxic natural killer cell expansion associated with responders and regulatory T cell expansion and baseline immunosuppressive scavenger myeloid cells associated with non-responders. The findings highlight the critical role of host immune cells in influencing the efficacy of CAR T therapy and propose modulation of these cells as a potential strategy to enhance outcomes in next-generation GBM treatments.
10.1016/j.cell.2026.05.026
Jun 08 – Jun 15, 2026
Microstructural MRI combined with metabolic MRI to evaluate the progression-free survival of patients with glioblastoma at the early follow-up after tumor treating fields: a pilot study.
BMC MED IMAGING · Q1 JOURNAL - RANK #51/212
This exploratory pilot study aimed to evaluate the feasibility of using microstructural and metabolic MRI to assess TTFields or temozolomide treatment efficacy in postoperative glioblastoma patients and explore potential associations with progression-free survival. Ten patients were scanned using time-dependent diffusion MRI and chemical exchange saturation transfer MRI at baseline and 1-6 months after initiating treatment, with parameters such as Diameter, intracellular volume fraction, cell density, and pH-weighted changes computed via IMPULSED and magnetization transfer analyses. Results indicated distinct early reductions in the cellularity index within the TTFields group and different dynamic evolution trends in Diameter (F=5.042, P=0.035) and pH-weighted values (F=5.291, P=0.055) in patients with and without progression. These findings suggest that early changes in microstructural and metabolic MRI measures correlate with PFS and highlight the potential of multiparametric imaging in optimizing treatment for GBM.
10.1186/s12880-026-02482-1
A Phase 1 and Biodistribution study of Ifabotuzumab, a humanized agonistic EphA3-targeted antibody, in patients with recurrent glioblastoma.
CLIN CANCER RES · Q1 JOURNAL - RANK #29/326TOP-TIER
This phase 1, multi-site trial evaluated the safety, biodistribution, and tumor targeting of the humanized agonistic EphA3 antibody ifabotuzumab and its zirconium-labeled PET imaging derivative in 12 adults with recurrent glioblastoma. Participants underwent PET scans with 89Zr-ifabotuzumab, followed by three infusions at 3.5 mg/kg or 5.25 mg/kg, and subsequent imaging; resected tumor samples were analyzed for biomarker expression using immunofluorescence and spatial transcriptomics. Results showed highly specific tumor uptake on PET, no non-specific binding, tolerance of both imaging and antibody infusions, and evidence of vascular modulation in some patients, with one patient maintaining prolonged stable disease. The study concludes ifabotuzumab is safe and selectively targets EphA3, supporting further clinical evaluation.
10.1158/1078-0432.CCR-25-3608
Jun 01 – Jun 08, 2026
Prospective randomized trial of tumor-treating fields with chemoradiation in newly diagnosed glioblastoma.
NEURO-ONCOL ADV · Q1 JOURNAL - RANK #50/285
This phase 2 prospective randomized trial assessed whether adding tumor-treating fields (TTFields) to standard radiotherapy (RT) and temozolomide (TMZ) improves outcomes in 66 patients with newly diagnosed glioblastoma. Participants were randomized to receive RT + TMZ with or without concurrent TTFields, followed in both arms by maintenance TMZ with TTFields; the primary endpoint was 1-year progression-free survival (PFS12) in the intention-to-treat (ITT) population. ITT analysis showed PFS12 of 28.7 % versus 17.3 % (p = 0.146), median PFS of 5.4 versus 4.13 months (p = 0.14) and median overall survival (OS) of 18.5 versus 16.5 months (p = 0.95) favoring the experimental arm; in an evaluable subgroup (n = 54), median PFS was significantly longer with TTFields (9.9 vs 4.1 months, p = 0.016). Adverse-event profiles were similar, leading authors to conclude that early integration of TTFields with chemoradiation is safe and warrants confirmation in larger trials.
10.1093/noajnl/vdag106
Phase 1 dose-escalation trial combining sulfasalazine and stereotactic radiosurgery in patients with recurrent glioblastoma.
REDOX BIOL · Q1 JOURNAL - RANK #15/319TOP-TIER
This phase 1 dose-escalation trial investigated combining sulfasalazine with stereotactic radiosurgery (SRS) for recurrent glioblastoma, using a 3+3 design with four dose levels (1.5-6.0 g) administered orally for 3 days before SRS. Twelve patients were enrolled; the primary endpoint was safety, with secondary endpoints including quality of life, glutathione levels, and tumor response. Two grade 3 adverse events (transient lymphocytopenia) occurred, quality of life remained stable, and intratumoral glutathione levels decreased (p=0.010). Objective RANO responses were observed in 5/11 patients versus 0/11 controls, with longer local tumor control (median 5.3 months, p<0.001) but equivalent overall survival (p=0.915).
10.1016/j.redox.2026.104241
Tumor-targeted interferon-α gene therapy for glioblastoma: a phase 1 trial.
NAT MED · Q1 JOURNAL - RANK #1/195TOP-TIER
This phase 1/2a dose-escalation study evaluated Temferon, a genetically engineered autologous stem cell transplant delivering interferon-α2 to the tumor microenvironment in 24 newly diagnosed glioblastoma patients with unmethylated MGMT promoter. The primary endpoint was safety and tolerability within 90 days post-infusion; no dose-limiting toxicities occurred up to the highest dose tested. Median overall survival was 16.7 months and progression-free survival was 8.1 months from diagnosis, with most patients maintaining good performance status. The authors conclude Temferon is a safe and tolerable immunotherapeutic strategy for newly diagnosed glioblastoma.
10.1038/s41591-026-04419-1
SEZ6-targeting antibody-drug conjugate ABBV-706 in advanced small cell lung cancer and solid tumors: a phase 1 trial.
NAT MED · Q1 JOURNAL - RANK #1/195TOP-TIER
This open-label, phase 1 clinical trial assessed the safety, tolerability, pharmacokinetics, immunogenicity, and antitumor activity of ABBV-706, a SEZ6-targeting antibody-drug conjugate, in 288 patients with advanced solid tumors, with a focus on 124 relapsed/refractory (R/R) small cell lung cancer (SCLC) patients. ABBV-706 was administered intravenously every 3 weeks, with safety outcomes highlighting anemia (61%) and fatigue (38%) as the most common treatment-related adverse events in the monotherapy cohort, and grade 3 or higher adverse events in 61% of R/R SCLC patients. Efficacy data showed an objective response rate of 52% in R/R SCLC, with comparable ORRs (56% and 59%) between 1.8 mg/kg and 2.5 mg/kg doses and median overall survival of 12.4 months at 1.8 mg/kg. The study concluded 1.8 mg/kg as the recommended phase 2 dose based on safety and efficacy.
10.1038/s41591-026-04452-0
May 25 – Jun 01, 2026
Long-Term Analysis of NRG Oncology RTOG 0539: A Phase II Trial of Observation for Low-Risk Meningioma and Radiotherapy for Intermediate- and High-Risk Meningioma.
J CLIN ONCOL · Q1 JOURNAL - RANK #6/326TOP-TIER
The study presents a prospective phase II trial (NRG Oncology RTOG 0539) on risk-adapted radiotherapy for WHO grade 1-3 meningioma patients. The primary objective was to assess the outcomes of observation for low-risk patients and radiotherapy for intermediate- and high-risk cohorts using a Kaplan-Meier analysis to estimate progression-free survival (PFS) and overall survival (OS) over a median follow-up of 11-12 years. Key results include 10-year PFS and OS rates of 85.2%/94.1% (low-risk), 72.2%/84.7% (intermediate-risk), and 42.5%/51.1% (high-risk), with grade 3+ radiotherapy toxicity rates of 9.6% and 15.1% in intermediate- and high-risk cohorts, respectively. The findings demonstrate the value of observation for low-risk patients and radiotherapy for higher-risk patients, while providing benchmarks for future trials.
10.1200/JCO-25-01441
Phase 1 evaluation of patients with newly diagnosed glioblastoma treated with radiation, nivolumab, and IDO1 enzyme inhibitor BMS-986205.
CLIN CANCER RES · Q1 JOURNAL - RANK #29/326TOP-TIER
This phase 1 trial evaluated the safety and tolerability of radiotherapy (RT) combined with nivolumab and the IDO1 enzyme inhibitor BMS-986205 in newly diagnosed glioblastoma (GBM) patients. The study included two cohorts: MGMT unmethylated patients (Cohort A) receiving RT, nivolumab, and escalating BMS-986205 doses, and MGMT methylated patients (Cohort B) receiving BMS-986205 at 25mg daily with RT, nivolumab, and temozolomide (TMZ). Treatment-related adverse events were mostly lower grade, with dose-limiting toxicities (grade 3 transaminase increases) observed in 2 patients at 50mg and 3 patients at 100mg BMS-986205, leading to a recommended phase 2 dose of 50mg daily. The study concluded that the combination therapy is safe and established a recommended dose for further evaluation in MGMT-unmethylated GBM patients.
10.1158/1078-0432.CCR-26-1124
May 18 – May 25, 2026
Phase 1/2 study of a WT1 peptide-dosing emulsion in pediatric patients with recurrent/refractory diffuse intrinsic pontine glioma, glioblastoma, or anaplastic astrocytoma.
EUR J CANCER · Q1 JOURNAL - RANK #45/326
This first-in-child phase 1/2 clinical trial prospectively evaluated a WT1 peptide vaccine in 18 pediatric patients with recurrent/refractory DIPG, glioblastoma, or anaplastic astrocytoma. Patients received intradermal injections, with 3.5 mg determined as the phase 2 dose after no dose-limiting toxicities in phase 1 (n=4). The primary endpoint, 9-month overall survival, was 44.4% (90% CI: 24.4-65.9) for all patients and 27.3% (90% CI: 7.9-56.4) for DIPG patients, with median OS of 5.4 months for DIPG; the vaccine was not statistically effective as the lower CI did not exceed the prespecified 20% threshold, though WT1-specific immune responders showed significantly longer median OS (9.9 vs. 4.9 months, p=0.024). The authors concluded the vaccine was well tolerated and induced immune responses warranting further development. (NCT02750891)
10.1016/j.ejca.2026.116808