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

作者：D. Ross Camidge, Jair Bar, Hidehito Horinouchi, Jonathan W. Goldman, Fedor Moiseenko, Е. А. Филиппова, İrfan Çiçin, Tudor–Eliade Ciuleanu, Nathalie Daaboul, Chunling Liu, Penelope A. Bradbury, Mor Moskovitz, Nuran Katgı, Pascale Tomasini, Alona Zer, Nicolas Girard, Kristof Cuppens, Ji‐Youn Han, Shang‐Yin Wu, Shobhit Baijal, Aaron S. Mansfield, Chih‐Hsi S. Kuo, Kazumi Nishino, Se‐Hoon Lee, David Planchard, Christina S. Baik, Martha Li, Peter Ansell, Summer Xia, Ellen Bolotin, Jim Looman, Christine K. Ratajczak, Shun Lü · 发表于：Journal of Clinical Oncology · 年份：2024 · DOI：10.1200/jco.24.00720 · 被引用次数：170 · 研究领域：Lung Cancer Treatments and Mutations、Lung Cancer Diagnosis and Treatment、Lung Cancer Research Studies

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...