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Author Notes:

Email Address:Ragini Kudchadkar rkudcha@emory.edu

Conflict of Interest:Gonzalez reports grant support from Astellas; Ernst reports funding for speaker bureau from Astellas.

Conflict of Interest:Chmielowski reports consultancy and funding for speaker bureau from Genentech and BMS and funding for speaker bureau from Prometheus.

Conflict of Interest:Weber reports travel support and grant support from Astellas; Steinberg, Keating, Jie, and Chen are Astellas employees; the remaining authors had no disclosures.

Subjects:

Research Funding:

This study was supported by Astellas Pharma Global Development.

Medical writing support was funded by Astellas Pharma Global Development and provided by Kevin Ryder, PhD, from Complete Healthcare Communications (Chadds Ford, PA).

Keywords:

  • Docetaxel
  • melanoma
  • survivin protein
  • YM155

A phase 2, multicenter, open-label study of sepantronium bromide (YM155) plus docetaxel in patients with stage III (unresectable) or stage IV melanoma

Tools:

Journal Title:

Cancer Medicine

Volume:

Volume 4, Number 5

Publisher:

, Pages 643-650

Type of Work:

Article | Final Publisher PDF

Abstract:

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/m(2) ) in combination with YM155 (5 mg/m(2) 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/m(2) and 56 patients received 75 mg/m(2) 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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© 2014 The Authors.

This is an Open Access article distributed under the terms of the Creative Commons Attribution 3.0 Unported License ( http://creativecommons.org/licenses/by/3.0/), which permits making multiple copies, distribution, public display, and publicly performance, distribution of derivative works, provided the original work is properly cited. This license requires copyright and license notices be kept intact, credit be given to copyright holder and/or author.

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