特泊替尼治疗既往治疗的小细胞肺癌患者。
Tarlatamab for Patients with Previously Treated Small-Cell Lung Cancer.
机构信息
From Samsung Medical Center, Sungkyunkwan University School of Medicine (M.-J.A.), and Yonsei Cancer Center, Yonsei University College of Medicine (B.C.C.), Seoul, and Seoul National University Bundang Hospital, Seongnam (J.-S.L.) - all in South Korea; Vall d'Hebron University Hospital and Vall d'Hebron Institute of Oncology (E.F.) and Hospital de la Santa Creu i Sant Pau (M. Majem), Barcelona, Hospital Universitari i Politecnic La Fe, Valencia (O.J.-V.), and Hospital Universitario 12 de Octubre, CNIO-H12o Lung Cancer Unit, Complutense University and Ciberonc, Madrid (L.P.-A.) - all in Spain; the Department of Medical Oncology, Saint Loukas Hospital, Thessaloniki, Greece (I.K.); the Department of Respiratory Medicine, Okayama University Hospital, Okayama (K.O.), the Department of Thoracic Oncology, National Cancer Center Hospital East, Kashiwa (H.I.), and Wakayama Medical University Hospital, Wakayama (H.A.) - all in Japan; Klinische Abteilung für Pneumologie, Universitätsklinikum Krems, Krems, Austria (S. Handzhiev); the Department of Oncology and Radiotherapy and Early Phase Clinical Trials Center, Medical University of Gdansk, Gdansk, Poland (R.D.); the Department of Internal Medicine, Center for Integrated Oncology, University Hospital Cologne, Cologne (J.W.), Lungen Clinic, Airway Research Center North, German Center for Lung Research, Grosshansdorf (M.R.), and the Translational Oncology-Early Clinical Trial Unit, Comprehensive Cancer Center Mainfranken and Bavarian Cancer Research Center, Universitätsklinikum Würzburg, Würzburg (H.-D.H.) - all in Germany; Christie NHS Foundation Trust and University of Manchester, Manchester, United Kingdom (F.B.); West Virginia University Health Sciences Center, Morgantown (J.B.A.); the Department of Pulmonary Medicine, Erasmus MC Cancer Institute, Rotterdam, the Netherlands (A.-M.C.D.); Dana-Farber Cancer Institute, Harvard Medical School, Boston (J.S.); the Division of Hematology-Oncology, Hillman Cancer Center, University of Pittsburgh Medical Center, Pittsburgh (T.K.O.), and Fox Chase Cancer Center, Philadelphia (H.B.) - both in Pennsylvania; Winship Cancer Institute of Emory University, Atlanta (S.S.R.); Sarah Cannon Research Institute at Tennessee Oncology, Nashville (M.L.J.); and Amgen, Thousand Oaks, CA (S. Huang, S.M., M. Minocha, T.J., P.M., E.S.A.).
出版信息
N Engl J Med. 2023 Nov 30;389(22):2063-2075. doi: 10.1056/NEJMoa2307980. Epub 2023 Oct 20.
BACKGROUND
Tarlatamab, a bispecific T-cell engager immunotherapy targeting delta-like ligand 3 and CD3, showed promising antitumor activity in a phase 1 trial in patients with previously treated small-cell lung cancer.
METHODS
In this phase 2 trial, we evaluated the antitumor activity and safety of tarlatamab, administered intravenously every 2 weeks at a dose of 10 mg or 100 mg, in patients with previously treated small-cell lung cancer. The primary end point was objective response (complete or partial response), as assessed by blinded independent central review according to the Response Evaluation Criteria in Solid Tumors, version 1.1.
RESULTS
Overall, 220 patients received tarlatamab; patients had previously received a median of two lines of treatment. Among patients evaluated for antitumor activity and survival, the median follow-up was 10.6 months in the 10-mg group and 10.3 months in the 100-mg group. An objective response occurred in 40% (97.5% confidence interval [CI], 29 to 52) of the patients in the 10-mg group and in 32% (97.5% CI, 21 to 44) of those in the 100-mg group. Among patients with an objective response, the duration of response was at least 6 months in 59% (40 of 68 patients). Objective responses at the time of data cutoff were ongoing in 22 of 40 patients (55%) in the 10-mg group and in 16 of 28 patients (57%) in the 100-mg group. The median progression-free survival was 4.9 months (95% CI, 2.9 to 6.7) in the 10-mg group and 3.9 months (95% CI, 2.6 to 4.4) in the 100-mg group; the estimates of overall survival at 9 months were 68% and 66% of patients, respectively. The most common adverse events were cytokine-release syndrome (in 51% of the patients in the 10-mg group and in 61% of those in the 100-mg group), decreased appetite (in 29% and 44%, respectively), and pyrexia (in 35% and 33%). Cytokine-release syndrome occurred primarily during treatment cycle 1, and events in most of the patients were grade 1 or 2 in severity. Grade 3 cytokine-release syndrome occurred less frequently in the 10-mg group (in 1% of the patients) than in the 100-mg group (in 6%). A low percentage of patients (3%) discontinued tarlatamab because of treatment-related adverse events.
CONCLUSIONS
Tarlatamab, administered as a 10-mg dose every 2 weeks, showed antitumor activity with durable objective responses and promising survival outcomes in patients with previously treated small-cell lung cancer. No new safety signals were identified. (Funded by Amgen; DeLLphi-301 ClinicalTrials.gov number, NCT05060016.).
背景
Tarlatamab 是一种双特异性 T 细胞衔接免疫疗法，靶向 delta 样配体 3 和 CD3，在先前接受治疗的小细胞肺癌患者的 1 期试验中表现出有希望的抗肿瘤活性。
方法
在这项 2 期试验中，我们评估了先前接受治疗的小细胞肺癌患者每 2 周静脉输注 10mg 或 100mg 的 tarlatamab 的抗肿瘤活性和安全性。主要终点是根据实体瘤反应评估标准 1.1 由盲法独立中心评估的客观缓解（完全或部分缓解）。
结果
共有 220 名患者接受了 tarlatamab 治疗；患者之前接受过中位数为两线的治疗。在接受抗肿瘤活性和生存评估的患者中，10mg 组的中位随访时间为 10.6 个月，100mg 组为 10.3 个月。10mg 组 40%（97.5%置信区间 [CI]，29 至 52）的患者发生客观缓解，100mg 组 32%（97.5%CI，21 至 44）的患者发生客观缓解。在有客观缓解的患者中，59%（40/68 例）的缓解持续时间至少为 6 个月。在 10mg 组的 40 名患者中有 22 名（55%）和在 100mg 组的 28 名患者中有 16 名（57%）在数据截止时仍有客观缓解。10mg 组的中位无进展生存期为 4.9 个月（95%CI，2.9 至 6.7），100mg 组为 3.9 个月（95%CI，2.6 至 4.4）；9 个月时的总生存估计分别为 68%和 66%的患者。最常见的不良事件是细胞因子释放综合征（10mg 组为 51%，100mg 组为 61%）、食欲下降（分别为 29%和 44%）和发热（分别为 35%和 33%）。细胞因子释放综合征主要发生在治疗周期 1 期间，大多数患者的事件严重程度为 1 级或 2 级。10mg 组（1%的患者）发生 3 级细胞因子释放综合征的频率低于 100mg 组（6%）。因治疗相关不良事件而停止 tarlatamab 治疗的患者比例较低（3%）。
结论
在先前接受治疗的小细胞肺癌患者中，每 2 周给予 10mg 剂量的 tarlatamab 显示出抗肿瘤活性，具有持久的客观缓解和有希望的生存结果。未发现新的安全信号。（由 Amgen 资助；DeLLphi-301 ClinicalTrials.gov 编号，NCT05060016。）
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