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Weekly EZN-2208 (PEGylated SN-38) in Combination with Bevacizumab in Patients with Refractory Solid Tumors

Friday, November 08, 2013 — Poster Session III

10:00 a.m. – 12:00 p.m.

FAES Academic Center (Upper-Level Terrace)




  • W. Jeong
  • S. Park
  • A. Rapisarda
  • M. Eugeni
  • R. Kinders
  • A. Chen
  • G. Melillo
  • B. Turkbey
  • J.H. Doroshow
  • S. Kummar


Anti-angiogenics such as bevacizumab (Bev) have been shown to up-regulate HIF-1α. Camptothecin analogues, including SN-38, have been shown to inhibit HIF-1α in preclinical models. Thus, co-administration of EZN 2208 could offset the induction of HIF-1α following administration of Bev. We have conducted a trial of the combination of EZN 2208 (E) with Bev in patients with refractory solid tumors to determine the safety and tolerability, and to evaluate modulation of HIF-1α protein in tumor biopsies. Tumor biopsies are analyzed for HIF-1α protein levels using a validated immunoassay, and HIF-1α response genes are assessed using RTPCR. Twelve pts have been enrolled to date; Eight pts are evaluable for response; prolonged stable disease was observed in 2 pts: HCC 16 cycles, desmoplastic round cell tumor 7 cycles. Reduction in HIF-1α protein levels compared to baseline (post Bev alone) was seen in 4 of 5 pts (range 24% - 64%), with evidence of modulation of mRNA in 3 of 5 pt tumors evaluated. Conclusions: This clinical trial provides preliminary proof of mechanism demonstrating modulation of HIF-1α levels in tumors following administration of a camptothecin analog, EZN 2208.

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