SCI

2 July 2024

Telisotuzumab Vedotin Monotherapy in Patients With Previously Treated c-Met Protein-Overexpressing Advanced Non-Squamous EGFR-Wildtype NSCLC in the Phase 2 LUMINOSITY Trial

（Journal of Clinical Oncology; if=42.1）

  • Camidge DR, Bar J, Horinouchi H, Goldman J, Moiseenko F, Filippova E, Cicin I, Ciuleanu T, Daaboul N, Liu C, Bradbury P, Moskovitz M, Katgi N, Tomasini P, Zer A, Girard N, Cuppens K, Han JY, Wu SY, Baijal S, Mansfield AS, Kuo CH, Nishino K, Lee SH, Planchard D, Baik C, Li M, Ansell P, Xia S, Bolotin E, Looman J, Ratajczak C, Lu S. 

  • Correspondence: ross.camidge@cuanschutz.edu

Purpose 目的

Telisotuzumab vedotin (Teliso-V) is a c-Met-directed antibody-drug conjugate with a monomethyl auristatin E cytotoxic payload. The phase 2 LUMINOSITY trial (NCT03539536) aimed to identify the optimal c-Met protein-overexpressing non-small cell lung cancer (NSCLC) population for treatment with Teliso-V (stage 1) and expand the selected group for efficacy evaluation (stage 2). Stage 2 enrolled patients with non-squamous epidermal growth factor receptor (EGFR)-wildtype NSCLC.

Telisotuzumab vedotin（Teliso-V）是一种c-Met导向的抗体-药物偶联物，具有单甲基auristatin E细胞毒性有效载荷。2期LUMINOSITY试验（NCT03539536）旨在确定用Teliso-V治疗的最佳c-Met蛋白过度表达非小细胞肺癌（NSCLC）人群（1期），并扩大所选组以进行疗效评估（2期）。2期入选的非鳞状表皮生长因子受体（EGFR）-野生型NSCLC患者。

 

Methods 方法

Eligible patients had locally advanced/metastatic c-Met protein-overexpressing NSCLC and ≤2 prior lines of therapy (including ≤1 line of systemic chemotherapy). c-Met protein overexpression in non-squamous 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 every 2 weeks. Primary endpoint was overall response rate (ORR) by independent central review.

合条件的患者具有局部晚期/转移性c-Met蛋白过表达的NSCLC，且既往治疗线≤2条（包括≤1条全身化疗线）。c-Met蛋白在非鳞状EGFR野生型NSCLC中的过度表达被定义为≥25%的肿瘤细胞具有3+染色（高[≥50%3+]；中等[≥25%-<50%]）。Teliso-V以1.9 mg/kg每2周给药一次。主要终点为独立中心评的总有效率（ORR）。

 

Results 结果

In total, 172 patients with non-squamous EGFR-wildtype NSCLC received Teliso-V in stages 1 and 2. ORR was 28.6% (95% CI, 21.7-36.2; c-Met high, 34.6% [24.2-46.2]; c-Met intermediate, 22.9% [14.4-33.4]). Median duration of response was 8.3 months (95% CI, 5.6-11.3; c-Met high, 9.0 [4.2-13.0]; c-Met intermediate: 7.2 [5.3-11.5]). Median overall survival was 14.5 months (95% CI, 9.9-16.6; c-Met high, 14.6 [9.2-25.6]; c-Met intermediate, 14.2 [9.6-16.6]). Median progression-free survival was 5.7 months (95% CI, 4.6-6.9; c-Met high, 5.5 [4.1-8.3]; c-Met intermediate: 6.0 [4.5-8.1]). 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 was peripheral sensory neuropathy (7%).

总共有172名非鳞状EGFR野生型NSCLC患者在1期和2期接受了Teliso-V治疗。ORR为28.6%（95%CI，21.7-36.2；c-Met高，34.6%[24.2-46.2]；c-Met-中间体，22.9%[14.4-33.4]）。中位反应持续时间为8.3个月（95%可信区间，5.6-11.3；c-Met高值，9.0[4.2-13.0]；c-Met中间值：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-中等，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-中等：6.0[4.5-8.1]）。最常见的任何级别的治疗相关不良事件（AE）是周围感觉神经病变（30%）、周围水肿（16%）和疲劳（14%）；最常见的≥3级为周围感觉神经病变（7%）。

 

Conclusion 结论

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

Teliso-V与c-Met蛋白过表达的非鳞状EGFR野生型NSCLC的持久反应有关，尤其是在那些具有高c-Met的NSCLC中。AE通常是可控的。