Avid Bioservices Inc (CDMO)

[cjgaddy]

2-4-16 Annals of Surgical Oncology: Bavi+Sorafenib vs. Liver Cancer/HCC - murine xenograft tests and Ph.1 human data from Dr. Yopp's UTSW IST trial...

2-4-16: “Antibody-Mediated Blockade of Phosphatidylserine Enhances the Antitumor Effect of Sorafenib in Hepatocellular Carcinomas Xenografts”
Annals of Surgical Oncology - Translational Research & Biomarkers (pp 1-9)
Xiaoyun Cheng, Li Li, Philip E. Thorpe, Adam C. Yopp, Rolf A. Brekken, Xianming Huang
http://link.springer.com/article/10.1245%2Fs10434-016-5107-5
ABSTRACT - Background
Currently, the only FDA-approved systemic therapy for hepatocellular carcinoma (HCC) is the multi-receptor tyrosine kinase inhibitor, sorafenib, which provides only modest clinical benefit. We recently showed that treatment with a phosphatidylserine (PS) targeting agent suppresses tumor growth by targeting tumor vasculature & reactivating antitumor immunity.
METHODS
We tested the hypothesis that sorafenib increases PS exposure on tumor vasculature, thereby enhancing the antitumor efficacy of PS targeting. We evaluated the efficacy of combining a PS targeting agent (2aG4) with sorafenib in murine xenograft models of human HCC.
RESULTS
Our results demonstrate that combination of 2aG4 & sorafenib had a superior therapeutic effect over single agent therapy. Mechanistic studies showed that sorafenib significantly increased PS exposure on tumor vasculature; the percentage of PS-positive vessels increased from 19 to 52, 23 to 68, and 30 to 55 % in PLC/PRF/5, C3A, and Huh7 tumors, respectively. Combination therapy significantly decreased tumor microvessel density and the level of M2 macrophages, while increasing the apoptotic index of tumor endothelial cells and the frequency of M1 macrophages. Furthermore, we report the findings of a Phase I clinical study of bavituximab, a chimeric version of 2aG4, combined with sorafenib in HCC patients. The Phase I results demonstrate the appropriate dose of bavituximab to be given with sorafenib in future clinical trials.
CONCLUSIONS
Overall, these results strongly support the combination of bavituximab with sorafenib as a promising systemic therapeutic strategy for the treatment for advanced HCC patients.
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Xiaoyun Cheng & Li Li have contributed equally to this work.
Rolf Brekken & Xianming Huang are consultants to, have equity interest in, and have a sponsored research agreement with Peregrine Pharmaceuticals Inc.

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H. 1st Investigator-Sponsored (IST) Ph.I/II Trial (Bavi+Sorafenib vs. Liver Cancer/HCC, open-label, n=9+38=47)
...Note: Sorafenib = Onyx/Bayer's Nexavar - see http://www.nexavar.com
Protocol: http://clinicaltrials.gov/ct2/show/NCT01264705 UTSW: http://tinyurl.com/mwdc2ql ; (5 sites: 3/UTSW, Parkland-Hosp, Dallas/VA, PI=Dr. Adam Yopp)

2-4-16/Annals.Surg.Onco.(Brekken/Thorpe/Yopp/Xianming) article: Murine xenograft & Ph.1/human data http://tinyurl.com/gtk2qg8
...”Bavi+sorafenib combo had a superior therapeutic effect over single agent therapy.”

3-25-15: Dr. Adam Yopp (UTSW) Oral-pres./SSO (Liver-IST/Ph2-data) http://tinyurl.com/opkh5qy N=38(79%HepC, ECOG/0=34%): MTTP=6.7mos, MOS=6.1, MDSS=8.7, DCR=58%
=>Dr.Yopp's PDF: http://www.peregrineinc.com/images/stories/pdfs/yopp_sso_03-28-2015.pdf

1-16-15 ASCO Gastro-Symposium: Ph.2 data/n=38 (Adam Yopp), ”These clinical outcomes of TTP=6.7/DCR=58%/PFS=4mo are quite encouraging…” http://tinyurl.com/m9uz9mo

11-8-14 SITC'14: Ph.2 Correlative Studies data (biopsies B4/After) on 6pts, incl. KOL Dimitry Gabrilovich’s comments: http://tinyurl.com/pchzr6h

9-9-14 Enrollment complete. http://tinyurl.com/ktrfswj ; (ph2=38  Ph1=9)

4-4-12 AACR'12: Dr. Adam Yopp, ”promising safety profile to-date" http://tinyurl.com/7yrwqm7 (see #5591)

Feb'12-Sep'14 10+ times: CEO Steve King hints of future ex-US partner-driven Bavi+Sorafenib/LIVER trial in Asia-Pacific: http://tinyurl.com/nkaxtcc
......Articles & Data describe Liver Cancer challenges in Asian populations: http://tinyurl.com/7z7o8j9 & http://tinyurl.com/7z99cy4

12-1-10: PPHM's 1st IST (Liver Cancer) initiated at UTSW, ~56 patients - http://tinyurl.com/3xd3e6c
…Per S.King, 5-18-10/R&R, "We've had a lot of interest in running clinical trials with the compound from investigators who have either had prior experience with the drug or would like to study the drug in various settings. Potential IST indications include all the major solid tumor types. Of particular interest is Liver Cancer, in which we have a natural tie-in with our HCV program, Ovarian Cancer and Pancreatic Cancer, also very nicely supported by the prior data.”