Tocilizumab, Atezolizumab, and Stereotactic Radiation Therapy in Recurrent Glioblastoma: Primary Analysis of Safety and Efficacy of a Phase 2 Trial, NRG Oncology-BN010
Article
Bagley, SJ, Polley, MYC, Kotecha, RR et al. (2026). Tocilizumab, Atezolizumab, and Stereotactic Radiation Therapy in Recurrent Glioblastoma: Primary Analysis of Safety and Efficacy of a Phase 2 Trial, NRG Oncology-BN010
. INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, 10.1016/j.ijrobp.2026.09.013
Bagley, SJ, Polley, MYC, Kotecha, RR et al. (2026). Tocilizumab, Atezolizumab, and Stereotactic Radiation Therapy in Recurrent Glioblastoma: Primary Analysis of Safety and Efficacy of a Phase 2 Trial, NRG Oncology-BN010
. INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, 10.1016/j.ijrobp.2026.09.013
Purpose: Preclinical data suggest that fractionated stereotactic radiation therapy (FSRT) may sensitize immunologically cold tumors to immune checkpoint inhibition by stimulating neoantigen release and that inhibition of interleukin-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], and FSRT in patients with recurrent glioblastoma. Methods and Materials: A multicenter, single-arm, phase 2 trial was conducted with a safety run-in phase followed by a Simon’s 2-stage design. Patients received the combination of tocilizumab and atezolizumab administered on 28-day treatment cycles until disease progression, unacceptable toxicity, or for ≤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 by modified Response Assessment in Neuro-Oncology criteria. The window for assessment of the primary endpoint was 6 months from time of enrollment. The 2-stage design was used for the primary endpoint analysis to discriminate between true response rates of no more than 10% (null hypothesis) and ≥30% (alternative hypothesis). Secondary endpoints included the rates and severity of adverse events, progression-free survival, and overall survival. 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 Simon’s 2-stage design (n = 29). The study did not meet its primary endpoint (objective response rate 3.4%; 95% CI, 0.1%-17.8%). Median progression-free survival was 3.2 months (95% CI, 2.0-4.0), and median overall survival 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 recurrent glioblastoma but did not achieve the prespecified efficacy outcome.
