Phase I trial of SNS-595 in patients with advanced malignancies

Abstract

2099 Background: SNS-595 is a novel naphthyridine analog that induces a G2 cell cycle arrest in vitro and shows broad activity in xenograft and drug resistant tumor models. Methods: SNS-595 was administered to patients (pts) with advanced solid cancers every 3 weeks as an IV infusion over 10 minutes without premedications. Cohorts of 3–6 pts were accrued to doses based on a modified Fibonacci sequence. Results: As of 12/04 16 patients were treated in the first five cohorts at doses starting at 3 mg/m2 and advancing to 48 mg/m2. Tumor types included lung (4), adenocarcinoma of unknown primary (4), renal (3), ovarian, melanoma, bladder, sarcoma and cholangiocarcinoma (1 each). The median age was 57 years (range 46 to 74) and median ECOG PS was 1 (range 0–2). No dose limiting toxicity has been seen. Transient Grade 4 hematological toxicity (ANC <500/μL) was seen in 2 of 3 pts in cohort 5 (48 mg/m2). Non-hematologic toxicities were mild and all grade 1/2. PK samples were collected on treatment Day 1 and were assayed using a noncompartmental analysis. Plasma SNS-595 concentrations were determined using a validated LC-MS/MS assay. AUC increased proportionally with dose and mean AUC(0-Inf) were 6329±182, 12655±851 and 25440±9512 ng*hr/ml, respectively, for 12, 24 and 48 mg/m2 dose levels. The terminal half-life is approximately 19 hours. Conclusions: In this phase I study SNS 595 is well tolerated with consistent and predictable PK effects. Dose escalation is continuing. Further data will be presented. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Sunesis Sunesis Sunesis