A Phase II Study of Telisotuzumab Vedotin in Patients With c-MET-positive Stage IV or Recurrent Squamous Cell Lung Cancer (LUNG-MAP Sub-study S1400K, NCT03574753).
A Phase II Study of Telisotuzumab Vedotin in Patients With c-MET-positive Stage IV or Recurrent Squamous Cell Lung Cancer (LUNG-MAP Sub-study S1400K, NCT03574753).
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DOI：
10.1016/j.cllc.2020.09.013
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发表时间：
2021-05
影响因子：
3.6
通讯作者：
Papadimitrakopoulou VA
中科院分区：
文献类型：
--
作者：
Waqar SN;Redman MW;Arnold SM;Hirsch FR;Mack PC;Schwartz LH;Gandara DR;Stinchcombe TE;Leighl NB;Ramalingam SS;Tanna SH;Raddin RS;Minichiello K;Bradley JD;Kelly K;Herbst RS;Papadimitrakopoulou VA
Lung-MAP S1400K旨在评估c-MET阳性鳞状细胞癌（SCC）患者对telisotuzumab vedotin（一种靶向c-MET的抗体-药物偶联物）的反应。既往治疗的SCC伴c-MET阳性肿瘤患者（H评分≥150，Ventana SP44测定）被纳入2个队列：队列1（免疫检查点抑制剂naïve）和队列2（免疫检查点抑制剂难治性）。Telisotuzumab vedotin 2.7 mg/kg每3周静脉给予，直到疾病进展或不可接受的毒性。每6周进行一次疗效评估。主要终点是RECIST 1.1的反应。次要终点包括无进展生存期（PFS）、总生存期（OS）、队列内反应、反应持续时间和毒性。计划在20例可评估患者后进行中期分析，≥3例患者需要继续入组。49名患者（占筛选患者的14%）被分配到S1400K组，28名患者入组（队列1 15名，队列2 13名），23名患者符合条件。S1400K因缺乏功效于2018年12月21日关闭。队列1中报告2例缓解（缓解率9%，95% CI: 0-20%）（1例完全缓解，1例未证实部分缓解），10例病情稳定，疾病控制率为52%。中位OS和PFS分别为5.6和2.4个月。有3例5级事件（队列2中2例肺炎，队列1中1例支气管肺出血）。Telisotuzumab vedotin未能达到预先指定的应答，无法证明继续入组至S1400K是合理的。肺炎是在SCC患者中观察到的一种意想不到的毒性。
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 naïve) 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 RECIST 1.1. Secondary endpoints included progression-free survival (PFS), overall survival (OS), 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 12/21/2018 due to lack of efficacy. Two responses (response rate of 9%; 95% CI: 0–20%) were reported in cohort 1 (1 complete and 1 unconfirmed partial response), while 10 patients had stable disease with disease control rate of 52%. The median OS and PFS were 5.6 and 2.4 months. 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.
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影响因子：
7.3
作者：
Gao J;Aksoy BA;Dogrusoz U;Dresdner G;Gross B;Sumer SO;Sun Y;Jacobsen A;Sinha R;Larsson E;Cerami E;Sander C;Schultz N
通讯作者：
Schultz N
影响因子：
8.4
作者：
Eisenhauer, E. A.;Therasse, P.;Verweij, J.
通讯作者：
Verweij, J.
DOI：
10.1158/1078-0432.ccr-13-3473
发表时间：
2015-04-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Herbst RS;Gandara DR;Hirsch FR;Redman MW;LeBlanc M;Mack PC;Schwartz LH;Vokes E;Ramalingam SS;Bradley JD;Sparks D;Zhou Y;Miwa C;Miller VA;Yelensky R;Li Y;Allen JD;Sigal EV;Wholley D;Sigman CC;Blumenthal GM;Malik S;Kelloff GJ;Abrams JS;Blanke CD;Papadimitrakopoulou VA
通讯作者：
Papadimitrakopoulou VA
影响因子：
20.4
作者：
Guo, Robin;Berry, Lynne D.;Kris, Mark G.
通讯作者：
Kris, Mark G.
影响因子：
11.5
作者：
Wang, Jieyi;Anderson, Mark G.;Reilly, Edward B.
通讯作者：
Reilly, Edward B.