J Neurooncol：重大突破！基因疗法可使复发性胶质母细胞瘤患者的存活期翻倍

VBL’s lead compound VB-111 is the first highly targeted anti-angiogenic agent for the specific inhibition of tumor vascular growth to use VTS™, for cancer therapy. VB-111 is an IV-administered anti-angiogenic agent for the treatment of solid tumor indications, with current clinical trials in rGBM, thyroid cancer and ovarian cancer.

VBL has obtained fast track designation for VB-111 in the United States for prolongation of survival in patients with glioblastoma that has recurred following a treatment with standard chemotherapy and radiation; we have also received orphan drug designation in both the United States and Europe.

VBL designed VB-111 to address oncology indications, specifically solid tumors, by selectively targeting the blood vessels required for tumor growth and inducing the programmed cell-death process, or apoptosis, of cells in those blood vessels. VB-111’s mechanism of action is independent of tumor-specific mutations, which we believe makes it less susceptible to resistance and, therefore, potentially applicable for a broader patient population than current therapies. 

• Preclinical Insights: Preclinical pharmacological and toxicology studies on VB-111 have shown tissue specificity for the tumor tissue, no significant damage to normal non-cancerous tissues or to the normal blood vessels in the body, and a more than 90 percent reduction in metastatic lung cancer model with one injection, as well as similar efficacy in other tumor models.

• Phase I “all comers” Clinical Trial: We conducted our Phase 1 “all comers” clinical trial of VB-111 in the United States as an open-label, dose-escalating trial to assess the safety, pharmacokinetics and pharmacodynamics of VB-111 in 56 patients with advanced metastatic cancer. The trial was performed at multiple centers and was initiated as a single dose trial. A statistically significant improved overall survival in the VB-111 therapeutic dose cohort as compared to other cohorts was seen. In addition, there was a trend of improvement in the progression free survival rate in response to VB-111 at the therapeutic dose.  Following prolonged stability, a partial response, or both, in several patients after treatment with a single dose, we enrolled patients into two additionaldose cohorts who received multiple therapeutic doses of VB-111 in two specific tumor types.

• Phase I/II and Phase II Clinical Trials – top-line interim results from our ongoing Phase 2 study of VB-111 in patients with recurrent glioblastoma (rGBM) demonstrated a statistically significant improvement in overall survival in patients treated with VB-111 followed by VB-111 in combination with bevacizumab (Avastin®) upon disease progression, compared to patients treated with VB-111 followed by bevacizumab alone upon further progression (p=0.05).

   

  We are also conducting an exploratory Phase 2 clinical trial in the United States as an open-label, dose- escalating trial to assess the safety and efficacy of single or multiple doses of VB-111 in patients with advanced, recently progressive differentiated thyroid cancer that is unresponsive to radioactive iodine. Analysis performed in December 2014 showed that six patients (35%) in the therapeutic dose cohort (n=17) met the primary endpoint of 6-month progression-free survival using Response Evaluation Criteria in Solid Tumors (RECIST), compared to three patients (23%) in the low dose cohort (n=13). VB-111 was well-tolerated in both stages of this study, with no signs of clinically significant safety issues. The company will continue to follow the patients and shall provide a full Phase 2 report by the end of the first half of 2016.

  On May 30, 2015 at the 2015 American Society of Clinical Oncology (ASCO) Annual Meeting, VBL Therapeutics presented positive interim results from an investigator-initiated, Phase 1/2a of VB-111 in Recurrent Platinum-Resistant Mullerian (Ovarian) Cancer.  The data demonstrated promising evidence of clinical benefit in patients with recurrent platinum-resistant Müllerian cancer who received VB-111 in conjunction with weekly paclitaxel. The trial is conducted at Massachusetts General Hospital and Dana Farber Cancer Institute, Boston, MA under VBL’s IND. 

• Phase III Clinical trial – VBL Therapeutics’ pivotal Phase 3 GLOBE trial of VB-111 in rGBM is ongoing under a special protocol assessment granted by the FDA.