Washington University School of Medicine, St. Louis, MO.
SWOG Statistical Center, Seattle, WA; Fred Hutchinson Cancer Research Center, Seattle, WA.
Clin Lung Cancer. 2021 May;22(3):170-177. doi: 10.1016/j.cllc.2020.09.013. Epub 2020 Oct 14.
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.
Lung-MAP S1400K 旨在评估替利妥珠单抗维汀（一种针对 c-MET 的抗体药物偶联物）在 c-MET 阳性鳞状细胞癌（SCC）患者中的疗效。
先前接受过治疗的 c-MET 阳性肿瘤（H 评分≥150，Ventana SP44 检测）的 SCC 患者被纳入 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）。替利妥珠单抗维汀 2.7mg/kg 静脉输注，每 3 周 1 次，直至疾病进展或出现不可接受的毒性。每 6 周进行一次疗效评估。主要终点是根据实体瘤反应评估标准（RECIST）v1.1 评估的反应。次要终点包括无进展生存期、总生存期、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，需要≥3 例应答才能继续入组。
49 例患者（筛查患者的 14%）被分配到 S1400K，28 例患者入组（队列 1 15 例，队列 2 13 例），23 例患者符合条件。由于疗效不佳，S1400K 于 2018 年 12 月 21 日关闭。队列 1 报告了 2 例应答（应答率为 9%，95%置信区间，0%-20%），包括 1 例完全缓解和 1 例未确认的部分缓解，而 10 例患者疾病稳定，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 个月和 2.4 个月。有 3 例 5 级事件（2 例肺炎，均在队列 2 中，1 例支气管肺出血，在队列 1 中）。
替利妥珠单抗维汀未能达到预先规定的应答标准，无法证明继续进行 S1400K 研究是合理的。肺炎是在 SCC 患者中观察到的一种意外毒性。
