新型疗法和试验设计对于卡介苗不敏感的非肌层浸润膀胱癌（NMIBC）患者仍然是一项重要任务。评估抗PD-L1指向的durvalumab（D）疗法、D + BCG和D + EBRT联合治疗的安全性和初步疗效。在社区和学术中心进行了一项多中心1期试验。患者每3周静脉注射1120毫克的D，共8周期。D + BCG患者还每周接受全剂量膀胱内注射的BCG治疗6周，建议维持治疗。D + EBRT患者在第1周期中，同时接受EBRT（6 Gy× 3次）。术后，在3个月和6个月进行膀胱镜和尿液细胞学检查，6个月评估时需要进行膀胱活检。每种方案的推荐2期剂量（RP2D）是主要终点。次要终点包括毒性剖面和完全缓解率（CR）。共有28名患者接受了D（n = 3）、D + BCG（n = 13）和D + EBRT（n = 12）的治疗。全剂量D、全剂量BCG和6 Gy分数×3被确定为RP2D。有1名患者（4％）经历了自身免疫性肝炎的3级剂量限制性毒性事件。所有患者中有64％在3个月时实现了CR，在D、D + BCG和D + EBRT队列中分别为33％、85％和50％。12个月CR在所有患者中的达到了46％，D + BCG中的73％和D + EBRT中的33％。D联合膀胱内注射BCG或EBRT在BCG对非肌层浸润性膀胱癌无效的患者中证明是可行和安全的。鼓励人们进一步研究联合治疗方法的疗效。durvalumab联合疗法可安全地用于非肌层浸润性膀胱癌患者，以增加持久性缓解率。版权所有2023年欧洲泌尿外科协会。由Elsevier B.V.出版。保留所有权利。

Novel treatments and trial designs remain a high priority for bacillus Calmette-Guerin (BCG)-unresponsive non-muscle-invasive bladder cancer (NMIBC) patients.To evaluate the safety and preliminary efficacy of anti-PD-L1 directed therapy with durvalumab (D), durvalumab plus BCG (D + BCG), and durvalumab plus external beam radiation therapy (D + EBRT).A multicenter phase 1 trial was conducted at community and academic sites.Patients received 1120 mg of D intravenously every 3 wk for eight cycles. D + BCG patients also received full-dose intravesical BCG weekly for 6 wk with BCG maintenance recommended. D + EBRT patients received concurrent EBRT (6 Gy × 3 in cycle 1 only).Post-treatment cystoscopy and urine cytology were performed at 3 and 6 -mo, with bladder biopsies required at the 6-mo evaluation. The recommended phase 2 dose (RP2D) for each regimen was the primary endpoint. Secondary endpoints included toxicity profiles and complete response (CR) rates.Twenty-eight patients were treated in the D (n = 3), D + BCG (n = 13), and D + EBRT (n = 12) cohorts. Full-dose D, full-dose BCG, and 6 Gy fractions × 3 were determined as the RP2Ds. One patient (4%) experienced a grade 3 dose limiting toxicity event of autoimmune hepatitis. The 3-mo CR occurred in 64% of all patients and in 33%, 85%, and 50% within the D, D + BCG, and D + EBRT cohorts, respectively. Twelve-month CRs were achieved in 46% of all patients and in 73% of D + BCG and 33% of D + EBRT patients.D combined with intravesical BCG or EBRT proved feasible and safe in BCG-unresponsive NMIBC patients. Encouraging preliminary efficacy justifies further study of combination therapy approaches.Durvalumab combination therapy can be safely administered to non-muscle-invasive bladder cancer patients with the goal of increasing durable response rates.Copyright © 2023 European Association of Urology. Published by Elsevier B.V. All rights reserved.