根据间皮素的常见表达和间皮瘤活性报告，对间皮素靶向抗体-药物偶联物 anetumab ravtansine 与程序性细胞死亡 1 (PD-1) 抑制剂派姆单抗 (pembrolizumab) 联合进行评估。Anetumab ravtansine 的 1 期安全磨合进行了 anetumab ravtansine（6.5 mg/kg，静脉注射，每 3 周一次）和 pembrolizumab（200 mg，每 3 周静脉注射）的组合，随后在美国和加拿大国家癌症中心的医疗中心进行了 2 期随机化，选择联合用药或单独使用 pembrolizumab研究所的实验治疗临床试验网络。表达间皮素且之前接受过铂类治疗的胸膜间皮瘤患者符合资格。在第 1 阶段 (n = 12)，仅观察到一种剂量限制性毒性，并且不符合剂量减少的规则。在第 2 阶段，联合组（n = 18，2 例部分缓解 [PR]，11%）和派姆单抗组（n = 17，1 例 PR，6%；z = - 0.5523，p = 0.29116）。联合用药的中位 PFS 为 12.2 个月（95% CI 5.1-不可评估 [NE]），派姆单抗为 3.9 个月（95% CI 2.1-NE）（HR=0.55，p=0.20）。接受 anetumab ravtansine 治疗的可溶性间皮素基线水平较高的患者的中位 PFS 为 5 个月。治疗组之间 PFS 的数值差异不具有统计学意义，可能与样本量小于计划有关。高水平的可溶性间皮素应潜在地考虑选择不使用正在开发的可溶性间皮素中和的间皮素靶向疗法。版权所有 © 2024 Elsevier B.V. 保留所有权利。

The mesothelin-targeting antibody-drug conjugate anetumab ravtansine was evaluated in combination with the programmed cell death-1 (PD-1) inhibitor pembrolizumab based on the common expression of mesothelin and reports of activity in mesothelioma.A phase 1 safety run-in of the combination of anetumab ravtansine (6.5 mg/kg iv q3weeks) and pembrolizumab (200 mg, IV q3weeks) was conducted, followed by a phase 2 randomization to the combination or pembrolizumab alone at medical centers across the United States and Canada in the National Cancer Institute's Experimental Therapeutics Clinical Trials Network. Patients with pleural mesothelioma that expressed mesothelin and had previously received platinum-based therapy were eligible.In phase 1 (n = 12) only one dose limiting toxicity was observed and the rules for dose reduction were not met. In phase 2, there was no difference in the confirmed response rates between the combination group (n = 18, 2 partial responses [PR], 11 %) and the pembrolizumab group (n = 17, 1 PR, 6 %; z = -0.5523, p = 0.29116). The median PFS was 12.2 months (95 % CI 5.1-not evaluable [NE]) for the combination, and 3.9 months for pembrolizumab (95 % CI 2.1-NE)(HR=0.55, p = 0.20). Patients with high baseline levels of soluble mesothelin who received anetumab ravtansine had a median PFS of 5 months.The numeric difference in PFS between treatment groups was not statistically significant, likely related to a smaller than planned sample size. High levels of soluble mesothelin should potentially be considered to select against the use of mesothelin-targeting therapies in development that are neutralized by soluble mesothelin.Copyright © 2024 Elsevier B.V. All rights reserved.