SCI

14 September 2024

Sustained Clinical Benefit and Intracranial Activity of Tarlatamab in Previously Treated Small Cell Lung Cancer:DeLLphi-300 Trial Update

（Journal of Clinical Oncology；IF：42.1）

  • Dowlati A, Hummel HD, Champiat S, Olmedo ME, Boyer M, He K, Steeghs N, Izumi H, Johnson ML, Yoshida T, Bouchaab H, Borghaei H, Felip E, Jost PJ, Gadgeel S, Chen X, Yu Y, Martinez P, Parkes A, Paz-Ares L. Sustained Clinical Benefit and Intracranial Activity of Tarlatamab in Previously Treated Small Cell Lung Cancer: DeLLphi-300 Trial Update. J Clin Oncol. 2024 Aug 29:JCO2400553. doi: 10.1200/JCO.24.00553. Epub ahead of print. PMID: 39208379.

  • CORRESPONDING AUTHOR :Afshin Dowlati, MD, University Hospitals Seidman Cancer Center and Case Western,Reserve University, Cleveland, OH.e-mail: afshin.dowlati@case.edu.


ABSTRACT 摘要

Tarlatamab, a bispecific T-cell engager immunotherapy targeting delta-like ligand 3, has shown durable anticancer activity and manageable safety in previously treated small cell lung cancer (SCLC) in DeLLphi-300 phase I and DeLLphi-301 phase II trials. Here, we report extended follow-up of DeLLphi-300 (median follow-up, 12.1 months [range, 0.2-34.3]) in fully enrolled cohorts treated with tarlatamab ≥10 mg dose administered once every two weeks, once every three weeks, or once on day 1 and once on day 8 of a 21-day cycle (N 5 152). Overall, the objective response rate (ORR) was 25.0%; the median duration of response (mDOR) was 11.2 months (95% CI, 6.6 to 22.3), and the median overall survival (mOS) was 17.5 months (95% CI, 11.4 to not estimable [NE]). Among 17 patients receiving 10 mg tarlatamab once every two weeks, the ORR was 35.3%, the mDOR was 14.9 months (95% CI, 3.0 to NE), the mOS was 20.3 months (95% CI, 5.1 to NE), and 29.4% had sustained disease control with time on treatment ≥52 weeks. No new safety signals were identified. In modified Response Assessment in Neuro-Oncology Brain Metastases analyses, CNS tumor shrinkage of ≥30% was observed in 62.5% of patients (10 of 16) who had a baseline CNS lesion of ≥10 mm, including in a subset of patients with tumor shrinkage long after previous brain radiotherapy. In DeLLphi-300 extended follow-up, tarlatamab demonstrated unprecedented survival and potential findings of intracranial activity in previously treated SCLC.

Tarlatamab是一种靶向Delta样配体3的双特异性T细胞衔接免疫疗法，在DeLLphi-300 I期和DeLLphi-301 II期试验中，针对既往治疗的小细胞肺癌（SCLC）显示出持久的抗癌活性和可控的安全性。在此，我们报告了DeLLphi-300试验的延长随访结果（中位随访时间为12.1个月[范围为0.2-34.3个月]），所有队列均已入组，并接受了每两周一次、每三周一次或在21天周期中第1天和第8天各一次的Tarlatamab ≥10 mg剂量治疗（N=152）。总体而言，客观缓解率（ORR）为25.0%；中位缓解持续时间（mDOR）为11.2个月（95% CI, 6.6至22.3），中位总生存期（mOS）为17.5个月（95% CI, 11.4至无法估计[NE]）。在接受每两周一次10 mg Tarlatamab治疗的17名患者中，ORR为35.3%，mDOR为14.9个月（95% CI, 3.0至NE），mOS为20.3个月（95% CI, 5.1至NE），且29.4%的患者在治疗时间≥52周时仍维持疾病控制。未发现新的安全信号。在神经肿瘤学脑转移分析的改良反应评估中，62.5%的患者（16人中的10人）在基线中枢神经系统病灶≥10 mm的情况下，观察到肿瘤缩小≥30%，其中包括一部分之前接受脑部放疗后较久才出现肿瘤缩小的患者。DeLLphi-300延长随访显示，Tarlatamab在既往治疗的SCLC中展现了前所未有的生存率及潜在的颅内活性。


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