A phase 2, multicenter, open-label study of sepantronium bromide (YM155) plus docetaxel in patients with stage III (unresectable) or stage IV melanoma.
A phase 2, multicenter, open-label study of sepantronium bromide (YM155) plus docetaxel in patients with stage III (unresectable) or stage IV melanoma.
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第2阶段，棕褐色溴化物（YM155）的多中心，开放标签研究，以及III期（无法切除）或IV期黑色素瘤的患者中的多西烷。
DOI：
10.1002/cam4.363
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发表时间：
2015-05
期刊：
影响因子：
4
通讯作者：
Weber, Jeffrey
中科院分区：
文献类型：
--
作者：
Kudchadkar, Ragini;Ernst, Scott;Chmielowski, Bartosz;Redman, Bruce G.;Steinberg, Joyce;Keating, Anne;Jie, Fei;Chen, Caroline;Gonzalez, Rene;Weber, Jeffrey
Survivin是一种微管相关蛋白，被认为参与保存细胞活力和调节肿瘤细胞有丝分裂，并且在许多原发肿瘤类型中过度表达，包括黑色素瘤。YM155是一种一流的生存素抑制剂。这项2期研究的目的是评估不可切除的III期或IV期黑色素瘤患者接受YM155 +多西他赛联合治疗的6个月无进展生存（PFS）率。本研究分为两部分：第一部分确定多西他赛联合YM155耐受剂量，第二部分评估多西他赛联合YM155耐受剂量（75 mg/m2） （5 mg/m2 /天，每3周连续输注168 h）。主要终点为6个月PFS率。次要终点为客观缓解率（ORR）、1年总生存期（OS）、首次缓解至进展时间、临床获益率（CBR）和安全性。64例转移性黑色素瘤患者接受多西紫杉醇和YM155治疗。8例患者初始多西他赛剂量为100mg /m2, 56例患者初始多西他赛剂量为75mg /m2。每个独立审查委员会（IRC）的六个月PFS率为34.8% (n = 64; 95% CI, 21.3-48.6%)，每个研究者的六个月PFS率为31.3% （n = 64; 95% CI, 19.5-43.9%）。每个IRC的最佳ORR（完全缓解[CR] +部分缓解[PR]）为12.5%（8/64）。稳定病（SD）率为51.6% (33/64),CBR （CR + PR + SD）为64.1%（41/64）。估计1年生存率为56.3%。YM155是一种新型药物，当与多西他赛联合治疗黑色素瘤患者时显示出适度的活性。YM155总体耐受性良好，但未达到预定的主要疗效终点（即6个月PFS率≥20%）。
Survivin is a microtubule-associated protein believed to be involved in preserving cell viability and regulating tumor cell mitosis, and it is overexpressed in many primary tumor types, including melanoma. YM155 is a first-in-class survivin suppressant. The purpose of this Phase 2 study was to evaluate the 6-month progression-free survival (PFS) rate in patients with unresectable Stage III or IV melanoma receiving a combination of YM155 plus docetaxel. The study had two parts: Part 1 established the dose of docetaxel that was tolerable in combination with YM155, and Part 2 evaluated the tolerable docetaxel dose (75 mg/m2) in combination with YM155 (5 mg/m2 per day continuous infusion over 168 h every 3 weeks). The primary endpoint was 6-month PFS rate. Secondary endpoints were objective response rate (ORR), 1-year overall survival (OS) rate, time from first response to progression, clinical benefit rate (CBR), and safety. Sixty-four patients with metastatic melanoma were treated with docetaxel and YM155. Eight patients received an initial docetaxel dose of 100 mg/m2 and 56 patients received 75 mg/m2 of docetaxel. Six-month PFS rate per Independent Review Committee (IRC) was 34.8% (n = 64; 95% CI, 21.3–48.6%), and per Investigator was 31.3% (n = 64; 95% CI, 19.5–43.9%). The best ORR (complete response [CR] + partial response [PR]) per IRC was 12.5% (8/64). The stable disease (SD) rate was 51.6% (33/64), leading to a CBR (CR + PR + SD) of 64.1% (41/64). Estimated probability of 1-year survival was 56.3%. YM155 is a novel agent showing modest activity when combined with docetaxel for treating patients with melanoma. YM155 was generally well tolerated, but the predetermined primary efficacy endpoint (i.e., 6-month PFS rate ≥20%) was not achieved.
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影响因子：
8.4
作者：
AAMDAL, S;WOLFF, I;VERWEIJ, J
通讯作者：
VERWEIJ, J
影响因子：
45.3
作者：
Gradilone, A;Gazzaniga, P;Aglianò, AM
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2.2
作者：
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11.2
作者：
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45.3
作者：
BEDIKIAN, AY;WEISS, GR;BENJAMIN, RS
通讯作者：
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