Preliminary phase 2 results of ABT-751 in subjects with advanced renal cell carcinoma (RCC)

Abstract

4603 Background: There is currently no effective adjuvant therapy available for subjects with advanced RCC. ABT-751, an oral antimitotic agent that binds to the colchicine site of β-tubulin and prevents microtubule polymerization, has shown antitumor activity in various human xenograft models. In addition, signs of antitumor activity, consisting mainly of stable disease, were seen in subjects with RCC during phase 1 ABT-751 studies. Methods: This phase 2, open label, multi-center study evaluated safety and efficacy of ABT-751 in subjects with advanced RCC [N = 97: 43 subjects with no prior therapy (NPT), 54 subjects with prior therapy (PT)]. For each cycle, subjects received 200 mg ABT-751 orally once daily for 21 consecutive days followed by a 7-day break. Cycles were repeated until the subject met discontinuation criteria. Safety was assessed by adverse events (AEs) and laboratory evaluations. Time to progression (TTP) was analyzed using Kaplan-Meier methodology. Tumor response was assessed radiographically every 2 cycles using RECIST. Results: The median duration of therapy was 2 cycles (range 1 - 10). AEs were reported in 94/97 subjects, and 31/97 (32%) subjects experienced serious adverse events (SAEs). The most commonly reported AEs were asthenia (69%), constipation (59%), nausea (46%), and anorexia (44%). The most common Grade 3 or 4 AEs considered possibly or probably related to drug were asthenia (7%) and ileus (7%). The most common SAEs were carcinoma (6%) and ileus (6%). Thirteen subjects experienced SAEs considered possibly related to study drug, and the most common were ileus (5%) and diarrhea (2%). The median TTP was 3.8 months (95% CI = 3.6 - 4.1). One partial response was observed, and the subject is ongoing in Cycle 9. Two other subjects are experiencing minor responses (26% and 22% decrease in target lesions; ongoing in Cycles 6 and 9, respectively). To date, 17 subjects have had stable disease for 8 or more cycles (12 NPT and 5 PT), the longest duration being nearly one year. Conclusions: The 21-day dosing regimen appears to have an acceptable safety profile in phase 2 clinical trials. Prolonged stable disease and tumor responses suggest a potential benefit from ABT-751 therapy. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Abbott Laboratories Abbott Laboratories