Phase II study of synthadotin (SYN-D; ILX651) administered daily for 5 consecutive days once every 3 weeks (qdx5q3w) in patients (Pts) with inoperable locally advanced or metastatic melanoma

Abstract

7530 Background: SYN-D is a pentapeptide with a unique mechanism of action that potentially differs from microtubule stabilizers (taxanes and epothilones) and tubulin inhibitors (vinca alkaloids and other dolastatins) as it is postulated to inhibit microtubule nucleation. SYN-D has been chemically modified to improve pharmacological properties and is orally bioavailable with a therapeutic window potentially enhanced over previous generations of dolastatins. The substantial cardiovascular toxicity observed with previous dolastatins was not observed in the SYN-D phase I studies. Due to activity in melanoma observed both in xenograft models and in the phase I setting (Ebbinghaus, ASCO 2003), SYN-D is being evaluated in pts with locally advanced or metastatic melanoma. Methods: In this multi-institutional phase II study, SYN-D was administered at 28 mg/m2 IV for 30 mins qdx5q3w with response rate as the primary endpoint. The study was designed: to assess the feasibility of increasing SYN-D dose if <3/10 DLTs were observed during cycle 1 in the first 10 pts; with an early stopping rule after accrual of 25 pts in the event of no response. Pharmacokinetic blood draws were performed in cycle 1. Eligibility criteria: ECOG PS 0–1; no prior systemic chemotherapy; no active ocular melanoma; adequate organ function. Results: To date 20 pts have been treated; data on the first 15 as follows: M/F=10/5; age 30–75 (median 56); ECOG 0/1=11/4; treatment naïve/prior biologics=10/5; number of courses 24 (median 2). In the first 10 pts grade 3 or 4 non-dose-limiting, predictable (day 15), and self-limited neutropenia was seen in 2 (20%) and 3 (30%) pts, respectively. Other toxicities were grade1–2: alopecia (n=4); fatigue (n=3); and nausea/vomiting (n=3). To date, no sensory neuropathy, thrombocytopenia, anemia or cardiovascular toxicity has been observed. Due to lack of DLT in the first 10 pts, the dose of SYN-D was escalated to 34 mg/m2 in subsequent pts. Assessment of response is in progress. Conclusion: SYN-D is a safe, well-tolerated treatment in locally advanced and metastatic melanoma pts. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration ILEX Products, Inc., an affiliate of ILEX Oncology ILEX Products, Inc., an affiliate of ILEX Oncology ILEX Oncology, Inc. ILEX Products, Inc., an affiliate of ILEX Oncology ILEX, Inc ILEX Products, Inc., an affiliate of ILEX Oncology ILEX Products, Inc., an affiliate of ILEX Oncology