H Horinouchi, B C Cho, D R Camidge, K Goto, P Tomasini, Y Li, A Vasilopoulos, P Brunsdon, D Hoffman, W Shi, E Bolotin, V Blot, J Goldman
{"title":"一项1b期研究结果显示，telisotuzumab vedotin联合奥西替尼治疗c-Met蛋白过表达、egfr突变的局部晚期/转移性非小细胞肺癌（NSCLC）患者在先前使用奥西替尼后进展。","authors":"H Horinouchi, B C Cho, D R Camidge, K Goto, P Tomasini, Y Li, A Vasilopoulos, P Brunsdon, D Hoffman, W Shi, E Bolotin, V Blot, J Goldman","doi":"10.1016/j.annonc.2025.01.001","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Osimertinib is the standard first-line treatment for advanced epidermal growth factor receptor (EGFR)-mutated NSCLC. However, treatment resistance is inevitable and increased c-Met protein expression correlates with resistance. Telisotuzumab vedotin (Teliso-V) is an antibody-drug conjugate that targets c-Met protein overexpression. Herein, we report the results of a phase 1/1b trial evaluating Teliso-V plus osimertinib in patients with NSCLC after progression on osimertinib.</p><p><strong>Patients and methods: </strong>This multicenter, open-label study (NCT02099058) enrolled patients with advanced EGFR-mutated, c-Met protein-overexpressing, non-squamous NSCLC that had progressed on prior osimertinib. Patients received Teliso-V (intravenously, every 2 weeks) plus osimertinib (orally, 80 mg once daily). Teliso-V was evaluated at 1.6 mg/kg in a safety lead-in phase and escalated to 1.9 mg/kg. Dose expansion included both doses. Endpoints included safety and tolerability, pharmacokinetics, objective response rate (ORR), duration of response (DOR), and progression-free survival (PFS).</p><p><strong>Results: </strong>A total of 38 patients received Teliso-V (1.6 mg/kg, n=20; 1.9 mg/kg, n=18) plus osimertinib and were included in this analysis. No dose-limiting toxicities were observed. Most frequent any-grade treatment-emergent adverse events (TEAEs) were peripheral sensory neuropathy (50%), peripheral edema (32%), and nausea (24%). Most common grade 3/4 TEAEs were anemia (11%) and pulmonary embolism (8%). Five TEAEs led to death; none were reported as being related to Teliso-V or osimertinib. The pharmacokinetic profile of Teliso-V plus osimertinib was similar to Teliso-V monotherapy. After a median follow-up of 7.4 months, ORR was 50.0% per independent central review (ICR) (DOR not reached), and median PFS per ICR was 7.4 months (95% CI: 5.4, NR).</p><p><strong>Conclusions: </strong>Teliso-V plus osimertinib had promising activity and a manageable safety profile in patients with c-Met protein-overexpressing, EGFR-mutated non-squamous NSCLC after progression on osimertinib. This combination has the potential to address an unmet medical need in this patient population.</p><p><strong>Clinicaltrials: </strong></p><p><strong>Gov id: </strong>NCT02099058.</p>","PeriodicalId":8000,"journal":{"name":"Annals of Oncology","volume":" ","pages":""},"PeriodicalIF":56.7000,"publicationDate":"2025-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Results from a phase 1b study of telisotuzumab vedotin in combination with osimertinib in patients with c-Met protein-overexpressing, EGFR-mutated locally advanced/metastatic non-small cell lung cancer (NSCLC) after progression on prior osimertinib.\",\"authors\":\"H Horinouchi, B C Cho, D R Camidge, K Goto, P Tomasini, Y Li, A Vasilopoulos, P Brunsdon, D Hoffman, W Shi, E Bolotin, V Blot, J Goldman\",\"doi\":\"10.1016/j.annonc.2025.01.001\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Osimertinib is the standard first-line treatment for advanced epidermal growth factor receptor (EGFR)-mutated NSCLC. However, treatment resistance is inevitable and increased c-Met protein expression correlates with resistance. Telisotuzumab vedotin (Teliso-V) is an antibody-drug conjugate that targets c-Met protein overexpression. Herein, we report the results of a phase 1/1b trial evaluating Teliso-V plus osimertinib in patients with NSCLC after progression on osimertinib.</p><p><strong>Patients and methods: </strong>This multicenter, open-label study (NCT02099058) enrolled patients with advanced EGFR-mutated, c-Met protein-overexpressing, non-squamous NSCLC that had progressed on prior osimertinib. Patients received Teliso-V (intravenously, every 2 weeks) plus osimertinib (orally, 80 mg once daily). Teliso-V was evaluated at 1.6 mg/kg in a safety lead-in phase and escalated to 1.9 mg/kg. Dose expansion included both doses. Endpoints included safety and tolerability, pharmacokinetics, objective response rate (ORR), duration of response (DOR), and progression-free survival (PFS).</p><p><strong>Results: </strong>A total of 38 patients received Teliso-V (1.6 mg/kg, n=20; 1.9 mg/kg, n=18) plus osimertinib and were included in this analysis. No dose-limiting toxicities were observed. Most frequent any-grade treatment-emergent adverse events (TEAEs) were peripheral sensory neuropathy (50%), peripheral edema (32%), and nausea (24%). Most common grade 3/4 TEAEs were anemia (11%) and pulmonary embolism (8%). Five TEAEs led to death; none were reported as being related to Teliso-V or osimertinib. The pharmacokinetic profile of Teliso-V plus osimertinib was similar to Teliso-V monotherapy. After a median follow-up of 7.4 months, ORR was 50.0% per independent central review (ICR) (DOR not reached), and median PFS per ICR was 7.4 months (95% CI: 5.4, NR).</p><p><strong>Conclusions: </strong>Teliso-V plus osimertinib had promising activity and a manageable safety profile in patients with c-Met protein-overexpressing, EGFR-mutated non-squamous NSCLC after progression on osimertinib. This combination has the potential to address an unmet medical need in this patient population.</p><p><strong>Clinicaltrials: </strong></p><p><strong>Gov id: </strong>NCT02099058.</p>\",\"PeriodicalId\":8000,\"journal\":{\"name\":\"Annals of Oncology\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":56.7000,\"publicationDate\":\"2025-01-11\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Annals of Oncology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1016/j.annonc.2025.01.001\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Annals of Oncology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.annonc.2025.01.001","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ONCOLOGY","Score":null,"Total":0}
Results from a phase 1b study of telisotuzumab vedotin in combination with osimertinib in patients with c-Met protein-overexpressing, EGFR-mutated locally advanced/metastatic non-small cell lung cancer (NSCLC) after progression on prior osimertinib.
Background: Osimertinib is the standard first-line treatment for advanced epidermal growth factor receptor (EGFR)-mutated NSCLC. However, treatment resistance is inevitable and increased c-Met protein expression correlates with resistance. Telisotuzumab vedotin (Teliso-V) is an antibody-drug conjugate that targets c-Met protein overexpression. Herein, we report the results of a phase 1/1b trial evaluating Teliso-V plus osimertinib in patients with NSCLC after progression on osimertinib.
Patients and methods: This multicenter, open-label study (NCT02099058) enrolled patients with advanced EGFR-mutated, c-Met protein-overexpressing, non-squamous NSCLC that had progressed on prior osimertinib. Patients received Teliso-V (intravenously, every 2 weeks) plus osimertinib (orally, 80 mg once daily). Teliso-V was evaluated at 1.6 mg/kg in a safety lead-in phase and escalated to 1.9 mg/kg. Dose expansion included both doses. Endpoints included safety and tolerability, pharmacokinetics, objective response rate (ORR), duration of response (DOR), and progression-free survival (PFS).
Results: A total of 38 patients received Teliso-V (1.6 mg/kg, n=20; 1.9 mg/kg, n=18) plus osimertinib and were included in this analysis. No dose-limiting toxicities were observed. Most frequent any-grade treatment-emergent adverse events (TEAEs) were peripheral sensory neuropathy (50%), peripheral edema (32%), and nausea (24%). Most common grade 3/4 TEAEs were anemia (11%) and pulmonary embolism (8%). Five TEAEs led to death; none were reported as being related to Teliso-V or osimertinib. The pharmacokinetic profile of Teliso-V plus osimertinib was similar to Teliso-V monotherapy. After a median follow-up of 7.4 months, ORR was 50.0% per independent central review (ICR) (DOR not reached), and median PFS per ICR was 7.4 months (95% CI: 5.4, NR).
Conclusions: Teliso-V plus osimertinib had promising activity and a manageable safety profile in patients with c-Met protein-overexpressing, EGFR-mutated non-squamous NSCLC after progression on osimertinib. This combination has the potential to address an unmet medical need in this patient population.
期刊介绍：
Annals of Oncology, the official journal of the European Society for Medical Oncology and the Japanese Society of Medical Oncology, offers rapid and efficient peer-reviewed publications on innovative cancer treatments and translational research in oncology and precision medicine.
The journal primarily focuses on areas such as systemic anticancer therapy, with a specific emphasis on molecular targeted agents and new immune therapies. We also welcome randomized trials, including negative results, as well as top-level guidelines. Additionally, we encourage submissions in emerging fields that are crucial to personalized medicine, such as molecular pathology, bioinformatics, modern statistics, and biotechnologies. Manuscripts related to radiotherapy, surgery, and pediatrics will be considered if they demonstrate a clear interaction with any of the aforementioned fields or if they present groundbreaking findings.
Our international editorial board comprises renowned experts who are leaders in their respective fields. Through Annals of Oncology, we strive to provide the most effective communication on the dynamic and ever-evolving global oncology landscape.
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