A randomized phase 2 study of the thrombospondin-mimetic peptide ABT-510 in patients with previously untreated advanced renal cell carcinoma

Abstract

4607 Background: ABT-510 is a potent nonapeptide that mimics the antiangiogenic activity of the naturally occurring protein, thrombospondin-1. In 2 phase 1 studies in patients with solid tumors, ABT-510 was tolerated at doses up to 260 mg per day. The pharmacokinetic target of 100 ng/mL for >3 hours was achieved at doses ≥20 mg per day. Six of 13 patients (46%) with refractory renal cell carcinoma (RCC) were progression-free for 16 or more weeks on study. A phase 2 study evaluating the activity of ABT-510 in the first-line treatment of patients with advanced RCC has completed accrual. Methods: 103 patients were randomized to receive ABT-510 at 10 mg or 100 mg twice daily by subcutaneous injection. Dosing is continuous. The primary endpoint of the study is progression-free survival (PFS); secondary endpoints include response rate, overall survival, and performance status. Tumor progression is evaluated every 8 weeks by RECIST; safety is evaluated at every visit. Results: 103 patients are enrolled in the study; 42 remain active. Demographic data are available for 87 patients (55M/32F); the median age is 58 years (range 20–80), and the baseline ECOG Performance Score for all patients is 0 or 1. For the 88 patients with preliminary data, the 6-month progression-free rate is 24.6% (95% CI=11.9, 37.3). One confirmed partial response has been observed. The most frequent adverse events (AEs) include injection site reaction, asthenia, and pain. There were 314 reported AEs, of which 32 (10%) were serious adverse events (SAEs). 7 SAEs were possibly or probably drug-related. These included 2 events related to bleeding (hemoptysis, gastrointestinal hemorrhage) and 1 thrombotic event (deep vein thrombosis); other possibly or probably drug-related SAEs included dehydration, cardiogenic pulmonary edema, cardiomyopathy, and gastrointestinal ulcer. Conclusions: Based on these preliminary data, this was a well-tolerated therapy but provided no obvious improvement in efficacy compared to historical controls. Study of ABT-510 in combination with other antiangiogenic or targeted agents may be reasonable, given the excellent safety profile of ABT-510. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Abbott Laboratories Abbott Laboratories, AstraZeneca, Merck, Pfizer Abbott Laboratories, Celegene, Eli Lilly, Novartis Abbott Laboratories