A phase I/II study of sepantronium bromide (YM155, survivin suppressor) with paclitaxel and carboplatin in patients with advanced non-small-cell lung cancer.

Author(s): Kelly RJ,  Thomas A,  Rajan A,  Chun G,  Lopez-Chavez A,  Szabo E,  Spencer S,  Carter CA,  Guha U,  Khozin S,  Poondru S,  Van Sant C,  Keating A,  Steinberg SM,  Figg W,  Giaccone G

Journal: Ann Oncol

Date: 2013 Oct

Major Program(s) or Research Group(s): LUACRG

PubMed ID: 23857959

PMC ID: PMC3784336

Abstract: BACKGROUND: This phase I/II study examined the safety and efficacy of Sepantronium Bromide (S), a small-molecule selective survivin suppressant, administered in combination with carboplatin (C) and paclitaxel (P). PATIENTS AND METHODS: Forty-one patients were treated on study. Twenty-two patients received escalating doses of S (3.6-12 mg/m(2)) and 19 with untreated stage IV non-small-cell lung cancer (NSCLC) were treated with the maximum tolerated dose of 10 mg/m(2) in combination with standard doses of C (AUC6) and P (200 mg/m(2)) for six cycles. S was administered as a continuous intravenous infusion (CIVI) over 72 h in 21-day treatment cycles. Study end points included safety and toxic effect, response rate, progression-free and overall survival (PFS and OS), as well as exploratory pharmacodynamic correlates. RESULTS: Treatment with S was well tolerated, and toxic effects were mostly hematological in the phase II study. Two (11%) partial responses were observed with a median PFS of 5.7 months and median OS 16.1 months. Pharmacodynamic analysis did not demonstrate an association with response. CONCLUSION: The combination of S (10 mg/m(2)/day 72-h CIVI) administered with C and P every 3 weeks exhibited a favorable safety profile but failed to demonstrate an improvement in response rate in advanced NSCLC. CLINICAL TRIAL NUMBER: NCT01100931.