Replies to post #161109 on Avid Bioservices Inc (CDMO)

[BioBS2012]

FTM...what would be considered to be a good result? If the Sorafenib alone arm MOS is 6 months would the Bavi + Sorafenib arm MOS of 7 months be good enough? Or would 8 months or more be necessary to draw attention to these results? Is Sorafenib perhaps not as immunostimulatory as docetaxel?

While you wait for FTM's perspective, I will share mine. Given that this is an open lable trial, I would say 50% or more increase in MOS would be required to gain any attention. JMO

Below is the presentation on March 13 by Dr. Yopp on the interim results. As to how Sorafenib compares with Docetaxel with regards to PS flipping, I don't believe any such coparative data exists for the time being - JMO

Presentation Title:

Combination of Bavituximab and Sorafenib Inhibits HCC Growth: Results of Preclinical Data and a Phase I Study

Abstract Body:

HCC, the fastest growing cause of cancer deaths, presents at advanced stage and few therapy options. Bavituximab is a novel antibody targeting phosphatidylserine (PS), a membrane lipid externalized on cells promoting immune tolerence and immunosuppression. We hypothesize that sorafenib will upregulate PS exposure on HCC tumors providing targets for bavituximab shifting an immunosuppressive to immunoreactive milieu. In addition, we will demonstrate combination bavituximab and sorafenib can be given safely in patients with advanced HCC. Methods:Immunocompromised mice with orthotopic human HCC tumors (Huh7, C3A, or LC/PRF/5), were treated with sorafenib and tumors harvested and analyzed by IHC for vascular endothelium (anti-CD31) and PS exposure (2aG4, murine bavituximab analogue). Efficacy of sorafenib or 2aG4 or combination was evaluated in mice bearing LC/PRF/5 tumors. Tumor volume measured and microvascular density (anti-CD31) and macrophage recruitment and phenotype determined by IHC. In the phase I study, patients with advanced HCC and Child-Pugh A received escalating doses of bavituximab weekly (0.3, 1.0, and 3.0 mg/kg) and sorafenib 400 mg bid for 28 days. Results:Sorafenib treatment of HCC xenografts increased PS exposure in 1.7-2.9 fold compared to control in each model tested (p<0.01). Sorafenib and 2aG4 inhibited tumors more then single agent therapy (p<0.01). MVD was reduced 30% in combination therapy compared to sorafenib alone (p<0.01). Combination therapy increased M1 (pro-inflammatory) macrophages and sorafenib alone increased M2 (anti-inflammatory) macrophages. Phase I trial demonstrated maximum tolerated bavituximab dose of 3.0 mg/kg weekly and 400 mg BID sorafenib with no dose limiting toxicities. Toxicities were related to sorafenib and included hand-foot syndrome (22% grade II), fatigue (33% grade I) and anorexia (22% grade I). Conclusions:Sorafenib increases PS exposure on HCC vascular endothelium and when given in combination with the murine bavituximab analogue inhibits tumor growth greater than sorafenib alone by reactivating innate immunity. Bavituximab and sorafenib can be given safely in patients with advanced HCC.

[freethemice]

This is a one-arm trial. There is no comparison of bavi+sorafenib to sorafenib alone.
This is exactly why people have unreasonable expectations, because they don't
even do the most basic of checking as to what the facts are.