Phase I/II study of targeted gene delivery in vivo—intravenous infusions of Rexin-G—demonstrate significant biologic activity by FDG PET-CT without toxicity in patients with progressive chemo-resistant sarcoma, breast cancer and pancreatic cancer

Abstract

14509 Background: Rexin-G is the first and so far only targeted gene delivery system that has been tested in the clinic (Nature Reviews/Genetics, Vol.8, p.573, 2007). Rexin-G is a pathotropic (disease-seeking) nanoparticle bearing a cytocidal cyclin G1 gene, that when injected intravenously, seeks out and accumulates in cancerous lesions, thus, enhancing local concentrations within the tumors. The purpose of the Phase I/II studies is to evaluate the safety and potential efficacy of repeated intravenous infusions of Rexin-G in patients with rapidly progressive chemo-resistant sarcoma, breast cancer, and pancreatic cancer. Methods: In these Phase I/II open label studies, patients with all types of sarcoma, or carcinoma of the breast or pancreas, were treated with 1×10e11 cfu Rexin-G, administered i.v. over 5 minutes, 2 times a week for 4 weeks (Cumulative Dose = 8×10e11 cfu) followed by a 2-week rest period. Patients with Grade 1 or less toxicity were given a dose-escalation consisting of additional treatment cycles of 1×10e11 cfu three times a week (Cumulative Dose per cycle: 1.2×10e12 cfu). Results: Aggregate analysis showed that ten of 12 (83%) evaluable patients had SD at 4–6 weeks evaluation using RECIST, while 4 of 12 (33%) and 8 of 12 (67%) had a PR or SD respectively using International PET criteria, and 5 of 12 (42%) and 6 of 12 (50%) had a PR or SD respectively using CHOI criteria. Further, the CA19–9 levels were significantly reduced in 2 of 4 of patients with pancreatic cancer. Two patients with sarcoma underwent partial resection and showed 50–95% tumor necrosis. At 5-months follow-up, the median progression-free survival and the median over-all survival was >3 months for all cancer types. Conclusions: These studies indicate (i) that repeated infusions of Rexin-G are safe and well-tolerated at these dose levels, and (ii) that Rexin-G retards tumor growth, induces significant tumor necrosis, reduces tumor density, FDG uptake, and tumor marker activity in patients with rapidly progressive chemo- resistant sarcoma, breast cancer and pancreatic cancer. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Epeius Biotechnologies Corporation Epeius Biotechnologies Corporation Epeius Biotechnologies Corporation