A Phase I Study to Assess the Safety and Pharmacokinetics of Single-agent Lorvotuzumab Mertansine (IMGN901) in Patients with Relapsed and/or Refractory CD-56-positive Multiple Myeloma.
A Phase I Study to Assess the Safety and Pharmacokinetics of Single-agent Lorvotuzumab Mertansine (IMGN901) in Patients with Relapsed and/or Refractory CD-56-positive Multiple Myeloma.
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DOI：
10.1016/j.clml.2018.08.018
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发表时间：
2019-01
影响因子：
2.7
通讯作者：
Chanan-Khan, Asher
中科院分区：
文献类型：
--
作者：
Ailawadhi, Sikander;Kelly, Kevin R.;Vescio, Robert A.;Jagannath, Sundar;Wolf, Jeffrey;Gharibo, Mecide;Sher, Taimur;Bojanini, Leyla;Kirby, Maurice;Chanan-Khan, Asher
Lorvotuzumab mertansine是一种独特的靶向CD 56的抗体-药物偶联物，经常在多发性骨髓瘤细胞上表达。目前的单药I期试验描述了最大耐受剂量，安全性和初始疗效，以帮助未来的药物开发。尽管治疗进展显著改善了多发性骨髓瘤（MM）的结局，但它仍然是一种无法治愈的疾病。复发性和/或难治性MM患者具有侵袭性病程，结局较差，因此需要具有新治疗机制的药物。我们提出了一个完整的单药洛沃妥珠单抗mertansine，一个独特的抗体-药物偶联物靶向CD 56，这是经常在MM中表达的I期试验的结果。37例复发性MM患者参加了剂量递增I期临床试验，以确定洛沃妥珠单抗mertansine的最大耐受剂量（112 mg/m2），随后在最大耐受剂量的扩展阶段。尽管复发性和/或难治性MM患者比例较高（56.8%），但在42.9%的患者中观察到疾病稳定或更好，这些患者的缓解持续时间较长（中位数，15.5个月）。不良事件特征有利，3/4级不良事件发生率低，无输注相关反应。未检测到针对研究药物的体液应答。这项已完成的单药lorvotuzumab mertansine I期试验为该药物的安全性和临床活性信号提供了充分的证据，保证了其作为MM治疗联合方案的一部分进行进一步的临床开发。
Lorvotuzumab mertansine, a unique antibody–drug conjugate targeting CD56, is frequently expressed on multiple myeloma cells. The present phase I trial of the single agent describes the maximum tolerated dose, safety, and initial efficacy to aid future drug development. Despite therapeutic advancements that have significantly improved outcomes in multiple myeloma (MM), it remains an incurable disease. Patients with relapsed and/or refractory MM have an aggressive disease course, with inferior outcomes, necessitating the need for agents with novel therapeutic mechanisms. We present the results of a completed phase I trial of single-agent lorvotuzumab mertansine, a unique antibody-drug conjugate targeting CD56, which is frequently expressed in MM. Thirty-seven patients with relapsed MM were enrolled in a dose-escalation phase I clinical trial to determine the maximum tolerated dose of lorvotuzumab mertansine (112 mg/m2), followed by an expansion phase at the maximum tolerated dose. Despite a high proportion of patients with relapsed and/or refractory MM (56.8%), stable disease or better was noted in 42.9% of patients, and these patients had a long duration of response (median, 15.5 months). The adverse event profile was favorable, with a low incidence of grade 3/4 adverse events and no infusion-related reactions. No humoral responses were detected against the study drug. This completed phase I trial of single-agent lorvotuzumab mertansine provides ample evidence of safety and signals of clinical activity for this agent, warranting its further clinical development as part of combination regimens for the management of MM.
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影响因子：
11.4
作者：
Chim CS;Kumar SK;Orlowski RZ;Cook G;Richardson PG;Gertz MA;Giralt S;Mateos MV;Leleu X;Anderson KC
通讯作者：
Anderson KC
IMGN901（一种针对CD56靶向抗体 - 药物结合物）对CD56阳性实体瘤患者的I期研究。
影响因子：
3.4
作者：
Shah MH;Lorigan P;O'Brien ME;Fossella FV;Moore KN;Bhatia S;Kirby M;Woll PJ
通讯作者：
Woll PJ
影响因子：
6.5
作者：
Vij R;Siegel DS;Jagannath S;Jakubowiak AJ;Stewart AK;McDonagh K;Bahlis N;Belch A;Kunkel LA;Wear S;Wong AF;Wang M
通讯作者：
Wang M
影响因子：
2.7
作者：
Jagannath, Sundar;Vij, Ravi;Siegel, David S.
通讯作者：
Siegel, David S.
影响因子：
254.7
作者：
Siegel, Rebecca;Ma, Jiemin;Jemal, Ahmedin
通讯作者：
Jemal, Ahmedin