From the AACR March 2012 meeting inn Chicago:
Author Block: Adam Yopp, Yull Arriega, Amit Singal, John Mansour, Glen Balch, Phillip Thorpe. UT Southwestern Medical Center, Dallas, TX
Abstract Body: Background: HCC is the fastest growing cause of cancer-related deaths in the US, with the majority of patients presenting with advanced stage disease. Despite sorafenib being the only systemic therapy with proven efficacy in advanced HCC, the median survival for these patients is still less than one year. Sorafenib, in pre-clinical HCC models, upregulates phosphatidylserine (PS) exposure on tumor vascular endothelium. The phosphatidylserine (PS)-targeting antibody, bavituximab, given in combination with sorafenib has greater efficacy in pre-clinical HCC models than either therapy alone. Bavituximab acts by directing immune cells to destroy the PS-expressing tumor vasculature, and by reactivating tumor immunity.The aim of our study was to evaluate the maximum tolerated dose (MTD) of bavituximab in combination with 400 mg bid of sorafenib in patients with advanced HCC.
Methods: In this single institution, phase I study (NCT01264705), sorafenib-naive adult patients with measurable, advanced HCC, ECOG PS = 2, and Child-Pugh (CP) class A cirrhosis received escalating doses of bavituximab weekly (0.3, 1.0, and 3.0 mg/kg) and sorafenib 400 mg bid for 28 days.
Results: Median age of patients was 61(range 43-76) years and seven patients were male. Five patients had CP A5 and 4 patients had CP A6 cirrhosis. The majority of patients had underlying HCV (7/9), one patient had HBV and one patient had NASH. Five patients (4 TACE, 1 resection) received prior treatment. Four patients had metastatic disease at initiation of treatment. No dose limiting toxicities were seen at any dose level. No grade 3/4 treatment-related events in the first 28 days were noted. Common toxicities at all grades were related to sorafenib and included hand-foot syndrome (33% grade I, 22% grade II), fatigue (33% grade I) and anorexia (22% grade I).
Conclusions: Bavituximab and sorafenib can be given safely in patients with advanced HCC at 3.0 mg/kg weekly and 400 mg bid, respectively. Hand-foot syndrome, fatigue and anorexia were the most common adverse events and are consistent with known adverse events with sorafenib therapy. These doses are currently being evaluated in an ongoing phase II study in this population.
