VBL Therapeutics Presents Positive Data on VB-111 in Advanced Radioactive Iodine Refractory Differentiated Thyroid Cancer at the ITC 2015 Conference
Multi-Cohort Phase 2 Trial Met Its Primary Endpoint of 6-Month PFS
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.
