Tocilizumab, atezolizumab, and stereotactic radiotherapy in recurrent glioblastoma: primary analysis of safety and efficacy of a phase 2 trial, NRG Oncology-BN010
In brief
A three-drug regimen produced responses in just 3.4% of recurrent glioblastomas
In this phase 2 trial, the combination of tocilizumab, atezolizumab and focused radiation produced an objective response in 3.4% of patients and failed to meet its prespecified efficacy target. Median survival was 10.2 months, and treatment was considered safe and well tolerated, but the single-arm study offers no evidence that the regimen improves outcomes.
- Journal
- International journal of radiation oncology, biology, physics (Q1)
- Published
- 29 September 2026
- Study design
- Non-randomized / quasi-experimental trial
- Evidence level
- Level 2, Moderate (CEBM 2b)
- Authors
- Stephen J Bagley, Mei-Yin C Polley, Rupesh R Kotecha, Steven Brem, Ranjini Tolakanahalli, Xiaobu Ye, et al.
- PMID
- 42810412
- DOI
- 10.1016/j.ijrobp.2026.09.013
Why clinicians should know about it
- Picked for Radiation Oncology (paper of the day, 1 October 2026): Phase 2 trial of FSRT combined with immunotherapy in recurrent
Abstract
BACKGROUND: Preclinical data suggest that fractionated stereotactic radiotherapy (FSRT) may sensitize immunologically-cold tumors to immune checkpoint inhibition by stimulating neoantigen release and that inhibition of interleukin-6 (IL-6) permits immunosuppressive tumor-associated macrophages to become immunostimulatory. This study aimed to test the safety and efficacy of the combination of tocilizumab (anti-IL6R), atezolizumab [anti-programmed death-ligand 1 (PD-L1)], and FSRT in patients with recurrent glioblastoma (rGBM). METHODS: A multicenter, single-arm, phase 2 trial was conducted with a safety run-in phase followed by a Simon's two-stage design. Patients received the combination of tocilizumab and atezolizumab administered on 28-day treatment cycles until disease progression, unacceptable toxicity, or for up to 2 years. FSRT (24 Gy in 3 fractions) was initiated 3-7 days following cycle 1 of systemic therapy. The primary endpoint was objective response rate (ORR) by modified Response Assessment in Neuro-Oncology (mRANO) criteria. The window for assessment of the primary endpoint was 6 months from time of enrollment. The two-stage design was used for the primary endpoint analysis to discriminate between true response rates of no more than 10% (null hypothesis) and at least 30% (alternative hypothesis). Secondary endpoints included the rates and severity of adverse events (AEs), progression-free survival (PFS), and overall survival (OS). RESULTS: Forty-one patients were eligible and evaluable. The safety run-in (n=12) established Dose Level 3 (combination of tocilizumab 8 mg/kg, FSRT, and atezolizumab 1680 mg) as the maximum tolerated dose, which was subsequently evaluated in the Simon's two-stage design (n=29). The study did not meet its primary endpoint (ORR 3.4%, 95% CI: 0.1% - 17.8%). Median PFS was 3.2 months (95% CI: 2.0 - 4.0), and median OS was 10.2 months (95% CI: 6.6 - 13.6). CONCLUSIONS: These findings suggest that the combination of tocilizumab, atezolizumab, and FSRT was safe and well tolerated in patients with rGBM but did not achieve the pre-specified efficacy outcome.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.