University of Colorado Cancer Center, Aurora, CO.
Multidisciplinary Oncology and Therapeutic Innovations Department, Aix Marseille University, Assistance Publique Hôpitaux de Marseille, Inserm U911 CRO2, Marseille, France.
J Clin Oncol. 2023 Feb 10;41(5):1105-1115. doi: 10.1200/JCO.22.00739. Epub 2022 Oct 26.
Overexpression of c-Met protein and epidermal growth factor receptor () mutations can co-occur in non-small-cell lung cancer (NSCLC), providing strong rationale for dual targeting. Telisotuzumab vedotin (Teliso-V), a first-in-class antibody-drug conjugate targeting c-Met, has shown a tolerable safety profile and antitumor activity as monotherapy. Herein, we report the results of a phase Ib study (ClinicalTrials.gov identifier: NCT02099058) evaluating Teliso-V plus erlotinib, an EGFR tyrosine kinase inhibitor (TKI), in patients with c-Met-positive (+) NSCLC.
This study evaluated Teliso-V (2.7 mg/kg once every 21 days) plus erlotinib (150 mg once daily) in adult patients (age ≥ 18 years) with c-Met+ NSCLC. Later enrollment required presence of an -activating mutation (-M) and progression on a prior EGFR TKI. End points included safety, pharmacokinetics, objective response rate (ORR), and progression-free survival (PFS). The efficacy-evaluable population consisted of c-Met+ patients (confirmed histology [H]-score ≥ 150) who had at least one postbaseline scan; c-Met+ patients with H-scores ≥ 225 were classified as c-Met high.
As of January 2020, 42 patients were enrolled (N = 36 efficacy-evaluable). Neuropathies were the most common any-grade adverse events reported, with 24 of 42 patients (57%) experiencing at least one event. The pharmacokinetic profile of Teliso-V plus erlotinib was similar to Teliso-V monotherapy. Median PFS for all efficacy-evaluable patients was 5.9 months (95% CI, 2.8 to not reached). ORR for -M patients (n = 28) was 32.1%. Of M patients, those who were c-Met high (n = 15) had an ORR of 52.6%. Median PFS was 6.8 months for non-T790M+ and for those whose T790M status was unknown, versus 3.7 months for T790M+.
Teliso-V plus erlotinib showed encouraging antitumor activity and acceptable toxicity in EGFR TKI-pretreated patients with -M+, c-Met+ NSCLC.
在非小细胞肺癌（NSCLC）中，c-Met 蛋白过表达和表皮生长因子受体（）突变可同时发生，为双重靶向治疗提供了强有力的理论依据。Telisotuzumab vedotin（Teliso-V）是一种首创的靶向 c-Met 的抗体药物偶联物，作为单药治疗已显示出可耐受的安全性和抗肿瘤活性。在此，我们报告了一项 I 期研究（ClinicalTrials.gov 标识符：NCT02099058）的结果，该研究评估了 Teliso-V（2.7mg/kg，每 21 天一次）联合表皮生长因子受体酪氨酸激酶抑制剂（TKI）厄洛替尼在 c-Met+ NSCLC 患者中的应用。
本研究纳入了年龄≥18 岁的 c-Met+ NSCLC 成年患者（ClinicalTrials.gov 标识符：NCT02099058），接受 Teliso-V（2.7mg/kg，每 21 天一次）联合厄洛替尼（150mg，每日一次）治疗。随后的入组要求存在-激活突变（-M）和既往 EGFR TKI 治疗后进展。主要终点包括安全性、药代动力学、客观缓解率（ORR）和无进展生存期（PFS）。疗效可评估人群包括至少有一次基线后扫描的 c-Met+患者（经组织学[H]-评分≥150）；H-评分≥225 的 c-Met+患者被归类为 c-Met 高。
截至 2020 年 1 月，共纳入 42 例患者（N=36 例可评估疗效的患者）。报告的最常见任何级别的不良事件是神经病变，42 例患者中有 24 例（57%）发生了至少一次事件。Teliso-V 联合厄洛替尼的药代动力学特征与 Teliso-V 单药治疗相似。所有疗效可评估患者的中位 PFS 为 5.9 个月（95%CI，2.8 至未达到）。-M 患者（n=28）的 ORR 为 32.1%。在 M 患者中，c-Met 高（n=15）患者的 ORR 为 52.6%。非 T790M+患者的中位 PFS 为 6.8 个月，而 T790M 状态未知的患者为 3.7 个月。
Teliso-V 联合厄洛替尼在 EGFR TKI 预处理的 -M+、c-Met+ NSCLC 患者中显示出令人鼓舞的抗肿瘤活性和可接受的毒性。
Zotero 插件