Telisotuzumab Vedotin与厄洛替尼联合用于治疗表达c-Met蛋白的非小细胞肺癌患者的Ib期研究

SCI 10 November 2022

Phase Ib Study of Telisotuzumab Vedotin in Combination With Erlotinib in Patients With c-Met Protein–Expressing Non–Small-Cell Lung Cancer

 (IF: JCO., 50.717)

Camidge DR, Barlesi F, Goldman JW, Morgensztern D, Heist R, Vokes E, Spira A, Angevin E, Su WC, Hong DS, Strickler JH, Motwani M, Dunbar M, Parikh A, Noon E, Blot V, Wu J, Kelly K. Phase Ib Study of Telisotuzumab Vedotin in Combination With Erlotinib in Patients With c-Met Protein-Expressing Non-Small-Cell Lung Cancer. J Clin Oncol. 2022 Oct 26:JCO2200739. 

Corresponding Author: D. Ross Camidge, MD, PhD, University of Colorado Cancer Center, 1665 Aurora Ct, Aurora, CO 80045; e-mail: Ross.Camidge@ucuanschutz.edu.

PURPOSE 目的

Overexpression of c-Met protein and epidermal growth factor receptor (EGFR) 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 (NCT02099058) evaluating Teliso-V plus erlotinib, an EGFR tyrosine kinase inhibitor (TKI), in patients with c-Met–positive (+) NSCLC. 

c-Met蛋白和表皮生长因子受体（EGFR）突变的过表达可能共同发生在非小细胞肺癌（NSCLC）中，这为双重靶向提供了强有力的理论依据。Telisouzumab vedotin（Teliso-V）是一种靶向c-Met的一种抗体药物偶联物，是一类原研新药，已显示出可耐受的安全性和作为单一疗法的抗肿瘤活性。在本文中，我们报告了一项Ib期研究（NCT02099058）的结果，该研究评估了c-Met阳性（+）NSCLC患者中评估Teliso-V联合厄洛替尼——一种EGFR酪氨酸激酶抑制剂（TKI）的疗效。

PATIENTS AND METHODS 患者与方法

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 EGFR-activating mutation (EGFR-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 post-baseline scan; c-Met+ patients with H-scores ≥ 225 were classified as c-Met high. 

本研究评估了Teliso-V（2.7 mg/kg，每21天一次）联合厄洛替尼（150 mg，每天一次）对 c-Met+ NSCLC成年患者（年龄≥18岁）的疗效。后来入组的患者需要存在EGFR激活突变 (EGFR-M+) 并在接受先前的 EGFR TKI 治疗后产生了疾病进展。终点包括安全性、药代动力学、客观缓解率（ORR）和无进展生存（PFS）。疗效可评估人群包括至少进行了一次基线后扫描的c-Met+患者（经证实的组织学[H]-评分≥ 150）；c-Met+患者H评分≥ 225的被归类为c-Met高。

RESULTS 结果

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 EGFR-M+ patients (n = 28) was 32.1%. Of EGFR-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+. 

截止2020年1月，有42名患者入组（N=36名疗效可评估）。神经病变是报告的最常见的任何级别的不良事件，42名患者中有24名（57%）至少经历过一次该事件。Teliso-V联合厄洛替尼的药代动力学特征与Teliso-V单药疗法相似。所有可评估疗效的患者的中位PFS为5.9个月（95% CI，2.8至未达到）。EGFR-M+患者（n=28）的ORR为32.1%。在EGFR-M+患者中，c-Met高的患者（n=15）ORR为52.6%。非T790M+患者和T790M状态未知的患者的PFS中位数为6.8个月，而T790M+为3.7个月。

CONCLUSION 结论

Teliso-V plus erlotinib showed encouraging antitumor activity and acceptable toxicity in EGFR TKI-pretreated patients with EGFR-M+, c-Met+ NSCLC.

Teliso-V联合厄洛替尼在EGFR TKI预处理的EGFR-M+、c-Met+的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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