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Abstract：
Lung-MAP S1400K was designed to evaluate the response to telisotuzumab vedotin, an antibody-drug conjugate targeting c-MET, in patients with c-MET-positive squamous cell carcinoma (SCC).
Patients with previously treated SCC with c-MET-positive tumors (H score ≥ 150, Ventana SP44 assay) were enrolled into 2 cohorts: Cohort 1 (immune checkpoint inhibitor-naive) and Cohort 2 (immune checkpoint inhibitor refractory). Telisotuzumab vedotin 2.7 mg/kg was administered intravenously every 3 weeks until disease progression or unacceptable toxicity. Response assessments were performed every 6 weeks. The primary endpoint was response by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Secondary endpoints included progression-free survival, overall survival, response within cohort, duration of response, and toxicities. Interim analysis was planned after 20 evaluable patients, with ≥ 3 responses needed to continue enrollment.
Forty-nine patients (14% of screened patients) were assigned to S1400K, 28 patients enrolled (15 in Cohort 1 and 13 in Cohort 2), and 23 were eligible. S1400K closed on December 21, 2018 owing to lack of efficacy. Two responses (response rate of 9%; 95% confidence interval, 0%-20%) were reported in cohort 1 (1 complete and 1 unconfirmed partial response), whereas 10 patients had stable disease, with a disease control rate of 52%. The median overall and progression-free survival was 5.6 and 2.4 months, respectively. There were 3 grade 5 events (2 pneumonitis, in Cohort 2, and 1 bronchopulmonary hemorrhage, in Cohort 1).
Telisotuzumab vedotin failed to meet the pre-specified response needed to justify continuing enrollment to S1400K. Pneumonitis was an unanticipated toxicity observed in patients with SCC.
Patients with previously treated SCC with c-MET-positive tumors (H score ≥ 150, Ventana SP44 assay) were enrolled into 2 cohorts: Cohort 1 (immune checkpoint inhibitor-naive) and Cohort 2 (immune checkpoint inhibitor refractory). Telisotuzumab vedotin 2.7 mg/kg was administered intravenously every 3 weeks until disease progression or unacceptable toxicity. Response assessments were performed every 6 weeks. The primary endpoint was response by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Secondary endpoints included progression-free survival, overall survival, response within cohort, duration of response, and toxicities. Interim analysis was planned after 20 evaluable patients, with ≥ 3 responses needed to continue enrollment.
Forty-nine patients (14% of screened patients) were assigned to S1400K, 28 patients enrolled (15 in Cohort 1 and 13 in Cohort 2), and 23 were eligible. S1400K closed on December 21, 2018 owing to lack of efficacy. Two responses (response rate of 9%; 95% confidence interval, 0%-20%) were reported in cohort 1 (1 complete and 1 unconfirmed partial response), whereas 10 patients had stable disease, with a disease control rate of 52%. The median overall and progression-free survival was 5.6 and 2.4 months, respectively. There were 3 grade 5 events (2 pneumonitis, in Cohort 2, and 1 bronchopulmonary hemorrhage, in Cohort 1).
Telisotuzumab vedotin failed to meet the pre-specified response needed to justify continuing enrollment to S1400K. Pneumonitis was an unanticipated toxicity observed in patients with SCC.
摘要：
Lung-MAPS1400K旨在评估对telisotuzumabvedotin的反应，靶向c-MET的抗体-药物缀合物，在c-MET阳性鳞状细胞癌（SCC）患者中。
将先前治疗过的SCC伴c-MET阳性肿瘤（H评分≥150，VentanaSP44测定）的患者纳入2个队列：队列1（免疫检查点抑制剂初治）和队列2（免疫检查点抑制剂难治性）。Telisotuzumabvedotin2.7mg/kg每3周静脉内施用直至疾病进展或不可接受的毒性。每6周进行反应评估。主要终点是实体瘤的反应评估标准（RECIST）v1.1。次要终点包括无进展生存期，总生存率,队列内的反应，响应的持续时间，和毒性。计划在20名可评估患者后进行中期分析，需要≥3次应答才能继续纳入。
49名患者（占筛查患者的14%）被分配到S1400K，28名患者（队列1中15名，队列2中13名），23人是合格的。由于缺乏疗效，S1400K于2018年12月21日关闭。两个反应(反应率为9%；95%置信区间，0％-20％）在队列1中报告（1个完全和1个未确认的部分反应），而10名患者病情稳定，疾病控制率为52%。中位总生存期和无进展生存期分别为5.6和2.4个月，分别。有3个5级事件（2个肺炎，在队列2和1支气管肺出血中，在队列1中）。
Telisotuzumabvedotin未能达到证明继续加入S1400K所需的预先指定的反应。肺炎是在SCC患者中观察到的意外毒性。
将先前治疗过的SCC伴c-MET阳性肿瘤（H评分≥150，VentanaSP44测定）的患者纳入2个队列：队列1（免疫检查点抑制剂初治）和队列2（免疫检查点抑制剂难治性）。Telisotuzumabvedotin2.7mg/kg每3周静脉内施用直至疾病进展或不可接受的毒性。每6周进行反应评估。主要终点是实体瘤的反应评估标准（RECIST）v1.1。次要终点包括无进展生存期，总生存率,队列内的反应，响应的持续时间，和毒性。计划在20名可评估患者后进行中期分析，需要≥3次应答才能继续纳入。
49名患者（占筛查患者的14%）被分配到S1400K，28名患者（队列1中15名，队列2中13名），23人是合格的。由于缺乏疗效，S1400K于2018年12月21日关闭。两个反应(反应率为9%；95%置信区间，0％-20％）在队列1中报告（1个完全和1个未确认的部分反应），而10名患者病情稳定，疾病控制率为52%。中位总生存期和无进展生存期分别为5.6和2.4个月，分别。有3个5级事件（2个肺炎，在队列2和1支气管肺出血中，在队列1中）。
Telisotuzumabvedotin未能达到证明继续加入S1400K所需的预先指定的反应。肺炎是在SCC患者中观察到的意外毒性。
