Sands Jacob, Ahn Myung-Ju, Lisberg Aaron, Cho Byoung Chul, Blumenschein George, Shum Elaine, Pons Tostivint Elvire, Goto Yasushi, Yoh Kiyotaka, Heist Rebecca, Shimizu Junichi, Lee Jong-Seok, Baas Paul, Planchard David, Pérol Maurice, Felip Enriqueta, Su Wu-Chou, Zebger-Gong Hong, Lan Lan, Liu Chelsea, Howarth Paul, Chiaverelli Rachel, Paz-Ares Luis
Dana-Farber Cancer Institute, Boston, MA.
National Cancer Center Hospital East, Kashiwa, Japan.
J Clin Oncol. 2025 Apr;43(10):1254-1265. doi: 10.1200/JCO-24-01349. Epub 2025 Jan 6.
Datopotamab deruxtecan (Dato-DXd) is a trophoblast cell-surface antigen-2-directed antibody-drug conjugate with a highly potent topoisomerase I inhibitor payload. The TROPION-Lung05 phase II trial (ClinicalTrials.gov identifier: NCT04484142) evaluated the safety and clinical activity of Dato-DXd in patients with advanced/metastatic non-small cell lung cancer (NSCLC) with actionable genomic alterations progressing on or after targeted therapy and platinum-based chemotherapy.
Patients received Dato-DXd 6 mg/kg once every 3 weeks. The primary end point was objective response rate (ORR) by blinded independent central review. Secondary end points included duration of response (DOR), safety, tolerability, and survival.
Among 137 patients who received at least 1 dose of Dato-DXd, 71.5% received at least three lines of prior therapies for advanced/metastatic disease. Overall, 56.9% had mutations and 24.8% had rearrangements. Median treatment duration was 4.4 months (range, 0.7-20.6). The confirmed ORR was 35.8% (95% CI, 27.8 to 44.4) overall, and 43.6% (95% CI, 32.4 to 55.3) and 23.5% (95% CI, 10.7 to 41.2) in those with mutations and rearrangements, respectively. The median DOR was 7.0 months (95% CI, 4.2 to 9.8), and the overall disease control rate was 78.8% (95% CI, 71.0 to 85.3). Grade ≥3 treatment-related adverse events (TRAEs) occurred in 28.5% of patients. The most common TRAE was stomatitis (preferred term; any grade: 56.2%; grade ≥3: 9.5%). Five (3.6%) patients experienced adjudicated treatment-related interstitial lung disease/pneumonitis, with 1 (0.7%) grade 5 event.
Encouraging and durable antitumor activity was observed with Dato-DXd in this heavily pretreated advanced/metastatic NSCLC population with actionable genomic alterations. The rate of treatment-related grade ≥3 toxicities was comparable with previous observations, and no new safety signals were observed.
达妥昔单抗德鲁替康（Dato - DXd）是一种靶向滋养层细胞表面抗原2的抗体药物偶联物，其有效载荷为高效拓扑异构酶I抑制剂。TROPION - Lung05 II期试验（ClinicalTrials.gov标识符：NCT04484142）评估了Dato - DXd在经靶向治疗和铂类化疗后疾病进展且具有可操作基因组改变的晚期/转移性非小细胞肺癌（NSCLC）患者中的安全性和临床活性。
患者每3周接受一次6 mg/kg的Dato - DXd治疗。主要终点是由盲态独立中央审查评估的客观缓解率（ORR）。次要终点包括缓解持续时间（DOR）、安全性、耐受性和生存率。
在137例接受至少1剂Dato - DXd治疗的患者中，71.5%的患者接受过至少三线针对晚期/转移性疾病的先前治疗。总体而言，56.9%的患者存在[具体基因突变]，24.8%的患者存在[具体基因重排]。中位治疗持续时间为4.4个月（范围0.7 - 20.6个月）。总体确认的ORR为35.8%（95%CI，27.8%至44.4%），在存在[具体基因突变]和[具体基因重排]的患者中分别为43.6%（95%CI，32.4%至55.3%）和23.5%（95%CI，10.7%至41.2%）。中位DOR为7.0个月（95%CI，4.2至9.8个月），总体疾病控制率为78.8%（95%CI，71.0%至85.3%）。28.5%的患者发生≥3级治疗相关不良事件（TRAEs）。最常见的TRAEs是口腔炎（首选术语；任何级别：56.2%；≥3级：9.5%）。5例（3.6%）患者发生经判定的治疗相关间质性肺疾病/肺炎，其中1例（0.7%）为5级事件。
在这一经过大量预处理且具有可操作基因组改变的晚期/转移性NSCLC患者群体中，观察到Dato - DXd具有令人鼓舞且持久的抗肿瘤活性。治疗相关≥3级毒性发生率与先前观察结果相当，未观察到新的安全信号。
