亚洲人最常见的黑色素瘤亚型是体部黑色素瘤，通常在晚期被诊断，并且对目前的程序性细胞死亡蛋白1（PD-1）抑制剂反应不良。为评估TQB2450和安乐蒂尼在晚期体部黑色素瘤患者中的安全性和疗效，进行了一个第Ib期研究（NCT03991975）。患者在剂量递增和剂量扩展阶段接受TQB2450（每3周1200 mg）和安乐蒂尼（每日1次10 mg或12 mg，2周内服药/1周停药）。主要终点是剂量限制性毒性（DLT）、最大耐受剂量（MTD）和客观疗效率（ORR）。2019年6月至2022年6月间，共有19名患者入组。大多数患者（19名患者中的16名）作为一线治疗接受了安乐蒂尼和TQB2450。未观察到DLT，也未达到MTD。19名患者中的18名（94.7%）经历了治疗相关不良事件（TRAEs），但大多数为1或2级。7名患者（36.8%）发生了3级或更高级别的TRAEs。ORR为26.3%（2例完全缓解和3例部分缓解）。疾病控制率为73.7%。响应的中位持续时间为30.3个月（95%可信区间：5.8-NA）。中位无进展生存期为5.5个月（95%可信区间：2.8-NA），中位总生存期为20.3个月（95%可信区间：14.8-NA）。全外显子测序结果表明，获得性药物耐药可能归因于MAPK信号通路的激活和转化为免疫抑制性肿瘤环境。与抗PD-1单药治疗相比，TQB2450与安乐蒂尼的联合应用在晚期体部黑色素瘤患者中显示出良好的耐受性和有希望的抗肿瘤活性，且PFS持续时间较长。本文受版权保护，保留所有权利。

Acral melanoma, the most common subtype of melanoma in Asians, is often diagnosed at an advanced stage, and responds poorly to current programmed cell death protein 1 (PD-1) inhibitors.To evaluate the safety and efficacy of TQB2450 and anlotinib in patients with advanced acral melanoma in a phase Ib study (NCT03991975).Patients received TQB2450 (1200 mg every 3 weeks) and anlotinib (10 mg or 12 mg once daily, 2-week on/1-week off) in the dose-escalation and dose-expansion phases. The primary endpoints were dose-limiting toxicity (DLT), maximum tolerated dose (MTD), and objective response rate (ORR).Nineteen patients were enrolled between June 2019 and June 2022. The majority of patients (16 of 19 patients) received anlotinib and TQB2450 as first-line treatment. No DLTs were observed and MTD was not reached. Eighteen (94.7%) out of 19 patients experienced treatment-related adverse events (TRAEs), but most were grade 1 or 2. Grade 3 or greater TRAEs occurred in 7 patients (36.8%). The ORR was 26.3% (2 complete responses and 3 partial responses). The disease control rate was 73.7%. The median duration of response was 30.3 months [95% confidence interval (CI): 5.8-NA]. The median progression-free survival was 5.5 months (95% CI: 2.8-NA) and median overall survival was 20.3 months (95% CI: 14.8-NA). Whole-exome sequencing suggested that acquired drug resistance might be attributed to activation of the MAPK signaling pathway and transformation to an immunosuppressive tumor environment.TQB2450 combined with anlotinib showed favorable tolerance and promising anti-tumor activity with a prolonged PFS compared with anti-PD1 monotherapy in patients with advanced acral melanoma.This article is protected by copyright. All rights reserved.