LUMINOSITY 2 期试验：对既往接受过治疗的 c-Met 蛋白过表达晚期非鳞状 EGFR 野生型 NSCLC 患者的 Telisotuzumab Vedotin 单药治疗。

IF 42.1 1区医学 Q1 ONCOLOGY Journal of Clinical Oncology Pub Date : 2024-09-01 Epub Date: 2024-06-06 DOI:10.1200/JCO.24.00720

D Ross Camidge, Jair Bar, Hidehito Horinouchi, Jonathan Goldman, Fedor Moiseenko, Elena Filippova, Irfan Cicin, Tudor Ciuleanu, Nathalie Daaboul, Chunling Liu, Penelope Bradbury, Mor Moskovitz, Nuran Katgi, Pascale Tomasini, Alona Zer, Nicolas Girard, Kristof Cuppens, Ji-Youn Han, Shang-Yin Wu, Shobhit Baijal, Aaron S Mansfield, Chih-Hsi Kuo, Kazumi Nishino, Se-Hoon Lee, David Planchard, Christina Baik, Martha Li, Peter Ansell, Summer Xia, Ellen Bolotin, Jim Looman, Christine Ratajczak, Shun Lu

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The phase II LUMINOSITY trial (ClinicalTrials.gov identifier: NCT03539536) aimed to identify the optimal c-Met protein-overexpressing non-small cell lung cancer (NSCLC) population for treatment with Teliso-V (stage I) and expand the selected group for efficacy evaluation (stage II). Stage II enrolled patients with nonsquamous epidermal growth factor receptor (EGFR)-wildtype NSCLC.Methods: Eligible patients had locally advanced/metastatic c-Met protein-overexpressing NSCLC and ≤2 previous lines of therapy (including ≤1 line of systemic chemotherapy). c-Met protein overexpression in nonsquamous EGFR-wildtype NSCLC was defined as ≥25% tumor cells with 3+ staining (high [≥50% 3+]; intermediate [≥25%-<50%]). Teliso-V was administered at 1.9 mg/kg once every 2 weeks. The primary end point was overall response rate (ORR) by independent central review.Results: In total, 172 patients with nonsquamous EGFR-wildtype NSCLC received Teliso-V in stages I and II. ORR was 28.6% (95% CI, 21.7 to 36.2; c-Met high, 34.6% [95% CI, 24.2 to 46.2]; c-Met intermediate, 22.9% [95% CI, 14.4 to 33.4]). The median duration of response was 8.3 months (95% CI, 5.6 to 11.3; c-Met high, 9.0 [95% CI, 4.2 to 13.0]; c-Met intermediate: 7.2 [95% CI, 5.3 to 11.5]). The median overall survival was 14.5 months (95% CI, 9.9 to 16.6; c-Met high, 14.6 [95% CI, 9.2 to 25.6]; c-Met intermediate, 14.2 [95% CI, 9.6 to 16.6]). The median progression-free survival was 5.7 months (95% CI, 4.6 to 6.9; c-Met high, 5.5 [95% CI, 4.1 to 8.3]; c-Met intermediate: 6.0 [95% CI, 4.5 to 8.1]). Most common any-grade treatment-related adverse events (AEs) were peripheral sensory neuropathy (30%), peripheral edema (16%), and fatigue (14%); the most common grade ≥3 AE was peripheral sensory neuropathy (7%).Conclusion: Teliso-V was associated with durable responses in c-Met protein-overexpressing nonsquamous EGFR-wildtype NSCLC, especially in those with high c-Met. 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引用次数: 0

摘要

目的：Telisotuzumab vedotin（Teliso-V）是一种具有单甲基auristatin E细胞毒性有效载荷的c-Met定向抗体药物共轭物。2期LUMINOSITY试验（NCT03539536）旨在确定接受Teliso-V治疗的最佳c-Met蛋白过表达非小细胞肺癌（NSCLC）人群（第1阶段），并扩大选定的疗效评估群体（第2阶段）。第二阶段招募非鳞状表皮生长因子受体（EGFR）野生型NSCLC患者：非鳞状表皮生长因子受体-野生型 NSCLC 中 c-Met 蛋白过表达的定义是：3+染色的肿瘤细胞≥25%（高[≥50% 3+]；中[≥25%-Results]）：共有172名非鳞状表皮生长因子受体-野生型NSCLC患者在1期和2期接受了泰利森-V治疗。ORR为28.6%（95% CI，21.7-36.2；c-Met高，34.6% [24.2-46.2]；c-Met中，22.9% [14.4-33.4]）。中位应答持续时间为 8.3 个月（95% CI，5.6-11.3；c-Met 高，9.0 [4.2-13.0]；c-Met 中，7.2 [5.3-11.3]）：7.2 [5.3-11.5]).中位总生存期为14.5个月（95% CI，9.9-16.6；c-Met高，14.6 [9.2-25.6]；c-Met中，14.2 [9.6-16.6]）。中位无进展生存期为 5.7 个月（95% CI，4.6-6.9；c-Met 高，5.5 [4.1-8.3]；c-Met 中，6.0 [4.5-8.3]）：6.0 [4.5-8.1]).最常见的任何等级的治疗相关不良事件（AEs）是外周感觉神经病变（30%）、外周水肿（16%）和疲劳（14%）；最常见的≥3级不良事件是外周感觉神经病变（7%）：结论：Teliso-V对c-Met蛋白过表达的非鳞状表皮生长因子受体-野生型NSCLC具有持久的疗效，尤其是对高c-Met的患者。AEs一般可控。

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Telisotuzumab Vedotin Monotherapy in Patients With Previously Treated c-Met Protein-Overexpressing Advanced Nonsquamous EGFR-Wildtype Non-Small Cell Lung Cancer in the Phase II LUMINOSITY Trial.

Purpose: Telisotuzumab vedotin (Teliso-V) is a c-Met-directed antibody-drug conjugate with a monomethyl auristatin E cytotoxic payload. The phase II LUMINOSITY trial (ClinicalTrials.gov identifier: NCT03539536) aimed to identify the optimal c-Met protein-overexpressing non-small cell lung cancer (NSCLC) population for treatment with Teliso-V (stage I) and expand the selected group for efficacy evaluation (stage II). Stage II enrolled patients with nonsquamous epidermal growth factor receptor (EGFR)-wildtype NSCLC.

Methods: Eligible patients had locally advanced/metastatic c-Met protein-overexpressing NSCLC and ≤2 previous lines of therapy (including ≤1 line of systemic chemotherapy). c-Met protein overexpression in nonsquamous EGFR-wildtype NSCLC was defined as ≥25% tumor cells with 3+ staining (high [≥50% 3+]; intermediate [≥25%-<50%]). Teliso-V was administered at 1.9 mg/kg once every 2 weeks. The primary end point was overall response rate (ORR) by independent central review.

Results: In total, 172 patients with nonsquamous EGFR-wildtype NSCLC received Teliso-V in stages I and II. ORR was 28.6% (95% CI, 21.7 to 36.2; c-Met high, 34.6% [95% CI, 24.2 to 46.2]; c-Met intermediate, 22.9% [95% CI, 14.4 to 33.4]). The median duration of response was 8.3 months (95% CI, 5.6 to 11.3; c-Met high, 9.0 [95% CI, 4.2 to 13.0]; c-Met intermediate: 7.2 [95% CI, 5.3 to 11.5]). The median overall survival was 14.5 months (95% CI, 9.9 to 16.6; c-Met high, 14.6 [95% CI, 9.2 to 25.6]; c-Met intermediate, 14.2 [95% CI, 9.6 to 16.6]). The median progression-free survival was 5.7 months (95% CI, 4.6 to 6.9; c-Met high, 5.5 [95% CI, 4.1 to 8.3]; c-Met intermediate: 6.0 [95% CI, 4.5 to 8.1]). Most common any-grade treatment-related adverse events (AEs) were peripheral sensory neuropathy (30%), peripheral edema (16%), and fatigue (14%); the most common grade ≥3 AE was peripheral sensory neuropathy (7%).

Conclusion: Teliso-V was associated with durable responses in c-Met protein-overexpressing nonsquamous EGFR-wildtype NSCLC, especially in those with high c-Met. AEs were generally manageable.

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来源期刊

Journal of Clinical Oncology 医学-肿瘤学

CiteScore

41.20

自引率

2.20%

发文量

8215

审稿时长

2 months

期刊介绍： The Journal of Clinical Oncology serves its readers as the single most credible, authoritative resource for disseminating significant clinical oncology research. In print and in electronic format, JCO strives to publish the highest quality articles dedicated to clinical research. Original Reports remain the focus of JCO, but this scientific communication is enhanced by appropriately selected Editorials, Commentaries, Reviews, and other work that relate to the care of patients with cancer.