Telisotuzumab Vedotin 联合厄洛替尼治疗 c-Met 蛋白表达的非小细胞肺癌的 Ib 期研究。
Phase Ib Study of Telisotuzumab Vedotin in Combination With Erlotinib in Patients With c-Met Protein-Expressing Non-Small-Cell Lung Cancer.
机构信息
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.
出版信息
J Clin Oncol. 2023 Feb 10;41(5):1105-1115. doi: 10.1200/JCO.22.00739. Epub 2022 Oct 26.
PURPOSE
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.
PATIENTS AND METHODS
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.
RESULTS
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+.
CONCLUSION
Teliso-V plus erlotinib showed encouraging antitumor activity and acceptable toxicity in EGFR TKI-pretreated patients with -M+, c-Met+ NSCLC.
目的
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。
方法
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。
结果
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。
结论
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。
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