University of Texas MD Anderson Cancer Center, Houston, TX, USA.
New York Medical College, Westchester Medical Center, Valhalla, NY, USA.
Eur Urol. 2022 Oct;82(4):365-373. doi: 10.1016/j.eururo.2022.05.002. Epub 2022 May 25.
Despite recent changes in the treatment landscape, there remains an unmet need for effective, tolerable, chemotherapy-free treatments for patients with advanced/metastatic urothelial carcinoma (mUC), especially cisplatin-ineligible patients.
To evaluate the immunostimulatory interleukin-2 cytokine prodrug bempegaldesleukin (BEMPEG) plus nivolumab in patients with advanced/mUC from the phase 2 multicenter PIVOT-02 study.
DESIGN, SETTING, AND PARTICIPANTS: This open-label, multicohort phase 1/2 study enrolled patients with previously untreated locally advanced/surgically unresectable or mUC (N = 41).
Patients received BEMPEG 0.006 mg/kg plus nivolumab 360 mg intravenously every 3 wk.
The primary objectives were safety and the objective response rate (ORR) in patients with measurable disease at baseline and at least one postbaseline tumor response assessment (response-evaluable). Secondary objectives were overall survival (OS) and progression-free survival (PFS). Exploratory biomarker analyses via univariate logistic regression were performed to test the association between potential biomarkers (CD8 tumor-infiltrating lymphocytes, tumor mutational burden, and IFN-γ gene expression profile) and response.
The ORR was 35% (13/37 evaluable patients) and the complete response rate was 19% (7/37 patients); the median duration of response was not reached. Median PFS was 4.1 mo (95% confidence interval [CI] 2.1-8.7) and median OS was 23.7 mo (95% CI 15.8-not reached). Overall, 40/41 patients (98%) experienced at least one treatment-related adverse event (TRAE); grade 3/4 TRAEs occurred in 11 patients (27%), most commonly pyrexia (4.9%; 2 patients). Exploratory biomarker analyses showed no association between biomarkers and response. Limitations include the small sample size and single-arm design.
BEMPEG plus nivolumab was well tolerated and showed antitumor activity as first-line treatment in patients with locally advanced/mUC.
We investigated an immune-stimulating prodrug called bempegaldesleukin plus the antibody nivolumab as the first therapy for patients with advanced or metastatic cancer of the urinary tract. This combination had manageable treatment-related side effects and was effective in a subset of patients. This trial is registered at ClinicalTrials.gov as NCT02983045.
尽管治疗领域最近发生了变化，但对于晚期/转移性尿路上皮癌（mUC）患者，尤其是不能耐受顺铂的患者，仍需要有效的、耐受良好的、无化疗治疗方法。
评估免疫刺激白细胞介素-2细胞因子前药bempegaldesleukin（BEMPEG）联合纳武利尤单抗在来自多中心 PIVOT-02 期研究的未经治疗的局部晚期/不可手术切除或 mUC 患者中的疗效。
设计、地点和参与者：这项开放标签、多队列的 1/2 期研究纳入了 41 例先前未经治疗的局部晚期/手术不可切除或 mUC 患者。
患者接受 BEMPEG 0.006mg/kg 联合纳武利尤单抗 360mg，每 3 周静脉注射一次。
主要目的是评估在基线和至少一次基线后肿瘤反应评估（可评估反应）时具有可测量疾病的患者的安全性和客观缓解率（ORR）。次要目的是总生存期（OS）和无进展生存期（PFS）。通过单变量逻辑回归进行探索性生物标志物分析，以检验潜在生物标志物（CD8 肿瘤浸润淋巴细胞、肿瘤突变负担和 IFN-γ基因表达谱）与反应之间的关联。
ORR 为 35%（37 例可评估患者中的 13 例），完全缓解率为 19%（37 例患者中的 7 例）；中位缓解持续时间未达到。中位 PFS 为 4.1 个月（95%置信区间 [CI]：2.1-8.7），中位 OS 为 23.7 个月（95%CI：15.8-未达到）。总体而言，41 例患者中有 40 例（98%）经历了至少一次与治疗相关的不良事件（TRAE）；11 例患者（27%）发生了 3/4 级 TRAE，最常见的是发热（4.9%；2 例）。探索性生物标志物分析显示，生物标志物与反应之间无关联。局限性包括样本量小和单臂设计。
BEMPEG 联合纳武利尤单抗作为局部晚期/mUC 患者的一线治疗药物，耐受性良好，具有抗肿瘤活性。
我们研究了一种名为 bempegaldesleukin 的免疫刺激前药，联合抗体 nivolumab 作为晚期或转移性尿路肿瘤患者的一线治疗药物。这种联合治疗的治疗相关副作用可管理，对部分患者有效。这项试验在 ClinicalTrials.gov 注册，编号为 NCT02983045。
