TEL AVIV, Israel, Oct. 21, 2015 (GLOBE NEWSWIRE) -- VBL Therapeutics (NASDAQ:VBLT), today announced positive results from its multi-cohort Phase 2 trial of VB-111 in advanced radioiodine-refractory differentiated thyroid cancer (RAIR-DTC). The pre-specified primary trial endpoint of 6-month Progression Free Survival (PFS) for at least 25% of enrolled patients was met, showing a dose response for VB-111. In the trial, which was conducted at the Mayo Clinic and Massachusetts General Hospital, VB-111 also demonstrated favorable safety and survival data, and a potential for dose-dependent disease stabilization. The results were presented today at the 15th International Thyroid Congress held in Orlando, FL.
The trial, which was designed to assess the safety and efficacy of VB-111, enrolled 29 patients with metastatic radioiodine resistant differentiated thyroid Cancer (RAIR-DTC), whose disease had progressed within the 6 months prior to enrollment. Most of the patients' cancers had previously not responded to various therapeutic interventions including radiation, tyrosine kinase inhibitors and cytotoxic agents. The primary endpoint required at least 25% of enrolled patients to achieve 6 month PFS.
The patients in this open-label, dose-escalating trial, were treated in two cohorts. In the first cohort, 12 patients received a single intravenous infusion of VB-111 at a low dose of 3X1012 viral particles (VPs). The second cohort included 17 patients who received VB-111 at a high dose of 1013 VPs every two months, until disease progression. Six patients (35%) in the high-dose cohort (n=17) met the primary endpoint of 6-month PFS using Response Evaluation Criteria in Solid Tumors (RECIST), compared to three patients (25%) in the low-dose cohort (n=12). PFS at 12 months was 25% in the VB-111 high-dose cohort, versus 0% in the low-dose cohort, potentially indicating dose-dependent disease stabilization. Several patients also had lesional objective responses, such as complete or partially resolved metastatic lesion or metastatic lymph node. To this point, patients in the trial have a median overall survival (OS) of 20 months: 18 months in the low-dose cohort and 22 months in the high-dose cohort. Nine patients remain alive – one in the low-dose cohort (8%) and eight in the high-dose cohort (47%), all of whom are beyond 18 months and still being followed.
"This Phase 2 trial was initiated following our Phase 1 'all comers' trial for VB-111, in which we noticed that the two patients enrolled with late-stage thyroid cancer each responded to treatment with VB-111," said Dror Harats, MD, CEO of VBL Therapeutics. "Meeting the primary endpoint of 6-month PFS in the current Phase 2 trial, along with the favorable overall survival data to date, further support the potential efficacy of VB-111 in patients with RAIR-DTC."
VB-111 was well tolerated in the majority of RAIR-DTC patients, consistent with the favorable safety and tolerability across more than 170 cancer patients in the VB-111 program. Adverse effects seen in the trial were generally modest, and mainly consisted of flu-like symptoms developing shortly after infusion. Severe adverse events were rare.
This positive efficacy signal is in line with the recently reported Phase 2 results of VB-111 for rGBM, which showed statistically significant overall survival benefit in patients treated with VB-111 continued with VB-111 in combination with Avastin™ upon disease progression, compared to patients treated with VB-111 followed by Avastin™ alone, upon disease progression. Similarly, in June, VBL Therapeutics reported positive results of VB-111 in recurrent ovarian cancer in combination with paclitaxel, showing encouraging response rates in heavily pre-treated platinum-resistant patients.
"VB-111 is an innovative, targeted anti-angiogenic agent that has shown efficacy results in clinical trials of three different cancer indications, as well as robust data in various animal models, including thyroid cancer. Together, we believe these data suggest that VB-111 may be an effective cancer therapy with a broad therapeutic potential," said Yael Cohen, MD, VP Clinical Development at VBL.
"Differentiated Thyroid Cancer is a prevalent cancer, with increasing incidence. While most patients respond favorably to surgery and radioactive iodine (RAI) therapy, a subset of patients develop resistant disease which is progressive, symptomatic and fatal. Kinase inhibitors have emerged as a new standard of care for such patients, but there remains a clear need for additional effective therapies. VB-111 represents a novel approach distinct from those otherwise available that may offer hope for these patients. In the present trial, the primary endpoint target for 6-month progression free survival was met, and several lesional responses were observed. A randomized controlled trial is required to more fully assess the efficacy and role of VB-111 in patients with RAI-refractory thyroid cancer," said Dr. Keith Bible, MD, PhD, of the Mayo Clinic Cancer center.
About Thyroid Cancer
Thyroid cancer occurs in the thyroid gland, a hormone-producing organ at the base of the neck that regulates heart rate, blood pressure, body temperature and weight. According to the National Cancer Institute, there are an estimated 535,000 people currently living with thyroid cancer in the United States, with an estimated 60,000 new cases each year and an estimated 1,850 annual deaths as a result of the disease. The type of treatment depends on the cancer cell type, tumor size and severity of the disease. First-line treatment is surgical removal of the thyroid gland, and is recommended for most patients. Treatment with radioactive iodine after surgery to destroy any remaining thyroid tissue may be recommended for more advanced disease. If radioactive iodine is ineffective, other treatments are prescribed, such tyrosine kinase inhibitors and systemic chemotherapy. However, if such treatments are unsuccessful, the therapeutic options for patients are currently very limited.
About the International Thyroid Congress (ITC)
The ITC is a collaborative meeting held every fifth year by the four world thyroid associations: ATA, Asia-Oceania Thyroid Association (AOTA), European Thyroid Association (ETA), and Latin American Thyroid Society (LATS). The meeting brings together the international community of endocrine specialists, surgeons and other health professionals to present and discuss the latest research and developments in thyroidology. This year's meeting is being held from Sunday October 18th to Friday, October 23rd, 2015 at the Walt DisneyWorld Swan and Dolphin Resort in Lake Buena Vista, Florida. For more information, refer to http://www.thyroid.org/itc2015/.
About VB-111
VB-111 is a novel, intravenously-administered, targeted anti-angiogenic agent that utilizes VBL's proprietary Vascular Targeting System (VTS™) to target endothelial cells in the tumor vasculature for cancer therapy. VB-111 contains a non-replicating adenovirus, a proprietary modified murine pre-proendothelin promoter (PPE-1-3x) and a Fas-Chimera transgene which is specifically activated in angiogenic tumor blood vessels, leading to their apoptosis.VB-111 is the first agent based on transcriptional targeting of tumor endothelium to be assessed in a clinical trial.
VB-111 completed a Phase 2 study in recurrent glioblastoma (rGBM), which showed a statistically significant improvement in overall survival in patients treated with VB-111 followed by VB-111 in combination with bevacizumab upon disease progression, compared to patients treated with VB-111 followed by bevacizumab alone. VB-111 is also being studied in a Phase 2a trial in recurrent platinum-resistant ovarian cancer, which provided promising evidence of clinical benefit in an interim analysis, and in a Phase 2a study in recurrent, iodine-resistant differentiated thyroid cancer, which provided evidence of disease stabilization and a positive safety profile. VB-111 has Fast Track Designation for recurrent glioblastoma in the U.S. and orphan drug status for glioblastoma in both the U.S. and EU.
About VBL
Vascular Biogenics Ltd., operating as VBL Therapeutics, is a late-stage clinical biopharmaceutical company focused on the discovery, development and commercialization of first-in-class treatments for cancer. The company's lead oncology product candidate, VB-111, is a gene-based biologic that is initially being developed for recurrent glioblastoma (rGBM), an aggressive form of brain cancer. VB-111 has received orphan drug designation in both the United States and Europe and was granted Fast Track designation by the FDA for prolongation of survival in patients with glioblastoma that has recurred following treatment with standard chemotherapy and radiation. VBL Therapeutics' pivotal Phase 3 GLOBE trial of VB-111 in rGBM is ongoing under a special protocol assessment granted by the FDA.
Forward-Looking Statements
This press release contains forward-looking statements. Forward-looking statements include all statements that do not relate solely to historical or current facts, and can be identified by the use of words such as "may," "will," "expect," "project," "estimate," "anticipate," "plan," "believe," "potential," "should," "continue" or the negative versions of those words or other comparable words. These forward-looking statements are not promises or guarantees and involve substantial risks and uncertainties. Among the factors that could cause actual results to differ materially from those described or projected herein include uncertainties associated generally with research and development, clinical trials and related regulatory reviews and approvals, and the risk that historical clinical trial results may not be predictive of future trial results. In particular, results from our proposed pivotal Phase 3 clinical trial of VB-111 in rGBM may not support approval of VB-111 for marketing in the United States. A further list and description of these risks, uncertainties and other risks can be found in the company's regulatory filings with the U.S. Securities and Exchange Commission. Existing and prospective investors are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof. VBL Therapeutics undertakes no obligation to update or revise the information contained in this press release, whether as a result of new information, future events or circumstances or otherwise.