International journal of radiation oncology, biology, physics · 2026
Tocilizumab, atezolizumab, and stereotactic radiotherapy in recurrent glioblastoma: primary analysis of safety and efficacy of a phase 2 trial, NRG Oncology-BN010.
СтатьяНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Bagley Stephen J, Polley Mei-Yin C, Kotecha Rupesh R, Brem Steven, Tolakanahalli Ranjini, Ye Xiaobu, Zureick Andrew H, Desai Arati, Cohen Adam L, Iwamoto Fabio M, Grogan Patrick T, Yogendran Lalanthica V, Odia Yazmin, Ney Douglas, Lobbous Mina, Mohler Alexander C, Zukas Alicia M, Kowalska Agnieszka, Kong Xiao-Tang, Green Richard M, Tuncer Tolga H, Haas Michael L, Gilbert Mark R, Won Minhee, Mehta Minesh P
Аннотация
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.
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.