铂类治疗后小细胞肺癌中的 Tambotatug Pelitecan
完整摘要 · 中文译文
背景：Tambotatug pelitecan（称为 Tam-Peli，一种靶向免疫检查点分子 B7-H3 的新型抗体药物偶联物）在早期试验中显示，对复发性广泛期小细胞肺癌患者具有令人鼓舞的临床疗效。 方法：在这项 3 期、多中心、开放标签、随机试验中，我们将符合条件的一线铂类治疗后进展的小细胞肺癌患者按 1:1 比例分配接受 tambotatug pelitecan 或拓扑替康治疗。主要终点为总生存期。关键次要终点为研究者评估的无进展生存期和客观缓解。此处，我们报告预设期中分析的结果。 结果：共451例患者接受了随机分组：225例被分配接受tambotatug pelitecan治疗，226例接受拓扑替康治疗。tambotatug pelitecan组的总生存期显著长于拓扑替康组——中位总生存期为13.3个月（95%置信区间[CI]，12.1至无法估计），而拓扑替康组为9.4个月（95% CI，7.7至10.5）；分层死亡风险比为0.46（95% CI，0.35至0.62；P<0.001）。与拓扑替康治疗相比，tambotatug pelitecan治疗还带来了显著更长的无进展生存期（中位数，7.4个月[95% CI，6.1至7.6] vs. 2.8个月[95% CI，1.8至3.0]；分层风险比，0.29[95% CI，0.23至0.37]；P<0.001）。tambotatug pelitecan组中59.1%的患者出现经确认的客观缓解，而拓扑替康组为9.7%（P<0.001）。tambotatug pelitecan组3级或以上不良事件的总发生率低于拓扑替康组（55.4% vs. 77.9%）。 结论：在铂类治疗后复发的广泛期小细胞肺癌患者中，与拓扑替康治疗相比，tambotatug pelitecan治疗带来了更长的总生存期、更长的无进展生存期、更高的客观缓解患者比例，且3级或以上不良事件发生率更低。（由“重大新药创制”国家科技重大专项和MediLink Therapeutics资助；TAISHAN-302 ClinicalTrials.gov编号，NCT06612151。）
完整摘要 · 英文原文
BACKGROUND: Tambotatug pelitecan (known as Tam-Peli, a new antibody-drug conjugate that targets the immune-checkpoint molecule B7-H3) showed promising clinical efficacy in patients with relapsed extensive-stage small-cell lung cancer in early-phase trials. METHODS: In this phase 3, multicenter, open-label, randomized trial, we assigned eligible patients with small-cell lung cancer that had progressed after first-line platinum-based therapy in a 1:1 ratio to receive tambotatug pelitecan or topotecan. The primary end point was overall survival. The key secondary end points were progression-free survival and objective response as assessed by investigators. Here, we report the results from the prespecified interim analysis. RESULTS: A total of 451 patients underwent randomization: 225 were assigned to receive tambotatug pelitecan and 226 to receive topotecan. Overall survival was significantly longer with tambotatug pelitecan than with topotecan - a median of 13.3 months (95% confidence interval [CI], 12.1 to could not be estimated), as compared with 9.4 months (95% CI, 7.7 to 10.5); the stratified hazard ratio for death was 0.46 (95% CI, 0.35 to 0.62; P<0.001). Treatment with tambotatug pelitecan also resulted in significantly longer progression-free survival than treatment with topotecan (median, 7.4 months [95% CI, 6.1 to 7.6] vs. 2.8 months [95% CI, 1.8 to 3.0]; stratified hazard ratio, 0.29 [95% CI, 0.23 to 0.37]; P<0.001). A confirmed objective response occurred in 59.1% of the patients in the tambotatug pelitecan group, as compared with 9.7% of those in the topotecan group (P<0.001). The overall incidence of adverse events of grade 3 or higher was lower with tambotatug pelitecan than with topotecan (55.4% vs. 77.9%). CONCLUSIONS: Among patients with relapsed small-cell lung cancer after platinum-based therapy, treatment with tambotatug pelitecan resulted in longer overall survival, longer progression-free survival, and a higher percentage of patients with an objective response than treatment with topotecan, with a lower incidence of adverse events of grade 3 or higher. (Funded by the Innovative Drug Research and Development National Science and Technology Major Project and MediLink Therapeutics; TAISHAN-302 ClinicalTrials.gov number, NCT06612151.).