巴卡菌卡麦特·格林（BCG）是切除膀胱肿瘤后治疗高危非肌层侵犯性膀胱癌（NMIBC）的标准治疗方法。然而，BCG后复发/进展经常发生，非膀胱切除选项有限。评估atezolizumab ± BCG在高风险BCG不响应的NMIBC中的安全性和临床活性。 这项Ib/2 相研究（NCT02792192）治疗了具有atezolizumab ± BCG的局部原位性膀胱癌反应不佳的NMIBC患者。1A和1B两组患者每3周静脉注射atezolizumab 1200mg，治疗时间≤96周。1B组还接受了标准BCG引导（每周六剂量）和维持疗程（从第3个月开始每周三次剂量），可选择在6个月、12个月、18个月、24个月和30个月进行维持治疗。主要终点是安全性和6个月的完全缓解（CR）率。次要终点包括3个月的CR率和CR持续时间;使用Clopper-Pearson方法计算95%的置信区间。数据截止（2020年9月29日），共有24名患者入组（1A组n = 12; 1B组n = 12），并且1B组使用的BCG剂量建议为50毫克。四名患者（33%）出现不良事件（AE）导致BCG剂量修正/中断。1A组中有3名患者（25％）报告了atezolizumab相关的3级AE; 1B组没有出现atezolizumab或BCG相关的≥3级AE。未报告任何4/5级AE。6个月的CR率分别为1A组33％（CR持续时间的中位数为6.8个月）和1B组42％（CR持续时间未达到[≥12个月]）。这些结果受GU-123样本大小的限制。在这份有关atezolizumab-BCG联合应用治疗NMIBC的第一份报告中，atezolizumab ± BCG耐受性良好，没有新的安全信号或治疗相关死亡。初步结果表明具有临床意义的活性;这种组合更有利于延长疗效。我们研究了atezolizumab加上或不加上卡介苗BCG，以确定这种组合是否安全，并且在先前接受过BCG治疗且仍然存在或再次出现的高风险非侵袭性膀胱癌（影响膀胱壁最外层的高级别膀胱肿瘤）患者中是否具有临床活性。我们的研究结果表明，atezolizumab加上或不加上BCG一般是安全的，并可用于治疗不响应BCG的患者。 版权所有©2023年欧洲泌尿学会。 由Elsevier B.V发表。所有权利保留。

Bacille Calmette-Guérin (BCG) is the standard therapy after transurethral resection of bladder tumour for high-risk non-muscle-invasive bladder cancer (NMIBC). However, post-BCG recurrence/progression occurs frequently, and noncystectomy options are limited.To evaluate the safety and clinical activity of atezolizumab ± BCG in high-risk BCG-unresponsive NMIBC.This phase 1b/2 GU-123 study (NCT02792192) treated patients with BCG-unresponsive NMIBC who had carcinoma in situ with atezolizumab ± BCG.Patients in cohorts 1A and 1B received atezolizumab 1200 mg IV q3w for ≤96 wk. Those in cohort 1B also received standard BCG induction (six weekly doses) and maintenance courses (three doses weekly starting at month 3) with optional maintenance at 6, 12, 18, 24, and 30 mo.Coprimary endpoints were safety and 6-mo complete response (CR) rate. Secondary endpoints included 3-mo CR rate and duration of CR; 95% confidence intervals were calculated using the Clopper-Pearson method.At data cut-off (September 29, 2020), 24 patients were enrolled (cohort 1A, n = 12; cohort 1B, n = 12), and the recommended BCG dose was 50 mg in cohort 1B. Four patients (33%) had adverse events (AEs) leading to BCG dose modification/interruption. Three patients (25%) in cohort 1A reported atezolizumab-related grade 3 AEs; cohort 1B had no atezolizumab- or BCG-related grade ≥3 AEs. No grade 4/5 AEs were reported. The 6-mo CR rate was 33% in cohort 1A (median duration of CR, 6.8 mo) and 42% in cohort 1B (median duration of CR, not reached [≥12 mo]). These results are limited by the small sample size of GU-123.In this first report of the atezolizumab-BCG combination in NMIBC, atezolizumab ± BCG was well tolerated, with no new safety signals or treatment-related deaths. Preliminary results suggested clinically meaningful activity; the combination favoured a longer duration of response.We studied atezolizumab with and without bacille Calmette-Guérin (BCG) to determine whether this combination was safe and had clinical activity in patients with high-risk noninvasive bladder cancer (high-grade bladder tumours that affect the outermost lining of the bladder wall) that has previously been treated with BCG and is still present or occurred again. Our results suggest that atezolizumab with or without BCG was generally safe and could be used to treat patients unresponsive to BCG.Copyright © 2023 European Association of Urology. Published by Elsevier B.V. All rights reserved.