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

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/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.YM155 is a first‐in‐class agent that suppresses surviving. Though YM155 combined with docetaxel was generally well‐tolerated in this study, it showed limited efficacy in the treatment of metastatic melanoma.