■免疫检查点抑制剂疗法在多种肿瘤类型中显示出令人印象深刻的临床益处。TQB2450是一种靶向程序性细胞死亡配体1的新型单克隆抗体,已在临床前研究中显示出安全性和有效性。
■这项首次人体研究旨在评估安全性/耐受性,药代动力学(PK),免疫原性,和TQB2450在晚期恶性肿瘤患者中的初步抗肿瘤活性。
■在这一阶段的研究中,符合条件的晚期恶性肿瘤患者每3周接受一次静脉TQB2450.该研究由3+3剂量递增阶段(1-30mg/kg)和特定剂量扩展阶段(1200mg)组成。主要终点是最大耐受剂量(MTD),剂量限制性毒性(DLT),和安全。次要终点是PK,免疫原性,和研究者评估的反应率。
■在2018年4月至2020年2月之间,招募了40名患者(22名处于剂量递增阶段,18名处于剂量扩大阶段)。未报告DLT,且未达到MTD。3级或更差的治疗相关治疗紧急不良事件(AE)发生在11名(27.50%)患者中,最常见的是天冬氨酸转氨酶升高(5.00%),白细胞减少症(5.00%),贫血(5.00%)。在6例患者中报告了与治疗相关的严重不良事件,其中最常见的是肝功能失代偿(5.00%)。没有治疗相关的死亡报告。TQB2450的最大血清浓度以剂量成比例的方式增加。31.58%(12/38)的患者检测到治疗诱导的抗药物抗体。研究者评估客观缓解率为5.00%,疾病控制率为52.50%,包括2个部分反应和19个稳定的疾病。中位无进展生存期为2.69(95%置信区间,2.07-6.14)个月。
■TQB2450具有可管理的安全性,具有良好的PK和免疫原性,并已显示出在晚期恶性肿瘤中具有临床活性的早期证据。
■NCT03460457。
UNASSIGNED: Immune checkpoint inhibitor therapy has demonstrated impressive clinical benefits in multiple tumor types. TQB2450, a novel monoclonal antibody targeting programmed cell death ligand 1, has shown safety and efficacy in preclinical studies.
UNASSIGNED: This first-in-human
study aimed to evaluate the safety/tolerability, pharmacokinetics (PK), immunogenicity, and preliminary antitumor activity of TQB2450 in patients with advanced malignant tumors.
UNASSIGNED: In this phase I
study, eligible patients with advanced malignant tumors received intravenous TQB2450 once every 3 weeks. This
study consisted of a 3 + 3 dose-escalation phase (1-30 mg/kg) and a specific dose-expansion phase (1200 mg). The primary endpoints were maximum tolerated dose (MTD), dose-limiting toxicity (DLT), and safety. The secondary endpoints were PK, immunogenicity, and investigator-assessed response rate.
UNASSIGNED: Between April 2018 and February 2020, 40 patients were enrolled (22 in the dose-escalation phase and 18 in the dose-expansion phase). No DLT was reported and the MTD was not reached. Grade ⩾3 or worse treatment-related treatment-emergent adverse events (AEs) occurred in 11 (27.50%) patients, with the most frequent being aspartate aminotransferase increased (5.00%), leukopenia (5.00%), and anemia (5.00%). Treatment-related serious AEs were reported in six patients, the most common of which was decompensated liver function (5.00%). No treatment-related death was reported. The maximum serum concentration of TQB2450 increased in a dose-proportional manner. Treatment-induced anti-drug antibodies were detected in 31.58% (12/38) of patients. The investigator assessed the objective response rate as 5.00% and the disease control rate was 52.50%, including 2 partial responses and 19 stable diseases. The median progression-free survival was 2.69 (95% confidence interval, 2.07-6.14) months.
UNASSIGNED: TQB2450 has a manageable safety profile with favorable PK and immunogenicity and has shown early evidence of clinical activity in advanced malignant tumors.
UNASSIGNED: NCT03460457.