Hospital Universitario 12 de Octubre, CNIO-H120 Lung Cancer Unit, Ciberonc and Universidad Complutense, Madrid, Spain.
Gustave Roussy, DC(c)partement d'Innovation ThC(c)rapeutique et d'Essais PrC(c)coces (DITEP), Villejuif, France.
J Clin Oncol. 2023 Jun 1;41(16):2893-2903. doi: 10.1200/JCO.22.02823. Epub 2023 Jan 23.
Small-cell lung cancer (SCLC) is an aggressive malignancy with limited treatments. Delta-like ligand 3 (DLL3) is aberrantly expressed in most SCLC. Tarlatamab (AMG 757), a bispecific T-cell engager molecule, binds both DLL3 and CD3 leading to T-cellb-mediated tumor lysis. Herein, we report phase I results of tarlatamab in patients with SCLC.
This study evaluated tarlatamab in patients with relapsed/refractory SCLC. The primary end point was safety. Secondary end points included antitumor activity by modified RECIST 1.1, overall survival, and pharmacokinetics.
By July 19, 2022, 107 patients received tarlatamab in dose exploration (0.003 to 100 mg; n = 73) and expansion (100 mg; n = 34) cohorts. Median prior lines of anticancer therapy were 2 (range, 1-6); 49.5% received antiprogrammed death-1/programmed death ligand-1 therapy. Any-grade treatment-related adverse events occurred in 97 patients (90.7%) and grade b % 3 in 33 patients (30.8%). One patient (1%) had grade 5 pneumonitis. Cytokine release syndrome was the most common treatment-related adverse event, occurring in 56 patients (52%) including grade 3 in one patient (1%). Maximum tolerated dose was not reached. Objective response rate was 23.4% (95% CI, 15.7 to 32.5) including two complete and 23 partial responses. The median duration of response was 12.3 months (95% CI, 6.6 to 14.9). The disease control rate was 51.4% (95% CI, 41.5 to 61.2). The median progression-free survival and overall survival were 3.7 months (95% CI, 2.1 to 5.4) and 13.2 months (95% CI, 10.5 to not reached), respectively. Exploratory analysis suggests that selecting for increased DLL3 expression can result in increased clinical benefit.
In patients with heavily pretreated SCLC, tarlatamab demonstrated manageable safety with encouraging response durability. Further evaluation of this promising molecule is ongoing.
小细胞肺癌（SCLC）是一种侵袭性恶性肿瘤，治疗方法有限。Delta-like 配体 3（DLL3）在大多数 SCLC 中异常表达。Tarlatamab（AMG 757）是一种双特异性 T 细胞衔接分子，与 DLL3 和 CD3 结合，导致 T 细胞介导的肿瘤裂解。在此，我们报告了 Tarlatamab 在 SCLC 患者中的 I 期研究结果。
这项研究评估了 Tarlatamab 在复发/难治性 SCLC 患者中的作用。主要终点是安全性。次要终点包括改良 RECIST 1.1 评估的抗肿瘤活性、总生存期和药代动力学。
截至 2022 年 7 月 19 日，107 例患者在剂量探索（0.003 至 100mg；n=73）和扩展（100mg；n=34）队列中接受了 Tarlatamab 治疗。中位既往抗癌治疗线数为 2 线（范围，1-6 线）；49.5%的患者接受了抗程序性死亡-1/程序性死亡配体-1 治疗。97 例患者（90.7%）发生任何级别治疗相关不良事件，33 例患者（30.8%）发生 3 级治疗相关不良事件。1 例患者（1%）发生 5 级肺炎。细胞因子释放综合征是最常见的治疗相关不良事件，发生于 56 例患者（52%），包括 1 例 3 级患者（1%）。未达到最大耐受剂量。客观缓解率为 23.4%（95%CI，15.7%至 32.5%），包括 2 例完全缓解和 23 例部分缓解。缓解持续时间的中位数为 12.3 个月（95%CI，6.6 至 14.9 个月）。疾病控制率为 51.4%（95%CI，41.5%至 61.2%）。中位无进展生存期和总生存期分别为 3.7 个月（95%CI，2.1 至 5.4 个月）和 13.2 个月（95%CI，10.5 个月至未达到）。探索性分析表明，选择表达增加的 DLL3 可导致临床获益增加。
在接受过多线治疗的 SCLC 患者中，Tarlatamab 表现出可管理的安全性，并具有令人鼓舞的持久缓解。正在对这种有前途的分子进行进一步评估。
