Additional Analyses Provide Insight into
Treatment Effect of VB-111
VBL Therapeutics (Nasdaq: VBLT), is reporting results today from
its Phase 3 GLOBE study in patients with recurrent glioblastoma
(rGBM) which was designed to evaluate VB-111 in combination with
bevacizumab (Avastin®) (`treatment arm`), compared to bevacizumab
(`control arm`). In March 2018, VBL announced top-line data
for the study, which did not demonstrate a benefit in overall
survival (OS) or progression-free survival for the treatment arm
relative to the bevacizumab control.
The GLOBE data are being presented today at the 2018 Society for
Neuro-Oncology Annual Meeting by Dr. Timothy Cloughesy, MD,
Professor of Clinical Neurology and Director of the Neuro-Oncology
Program, UCLA School of Medicine and principal investigator of the
GLOBE trial. The data include further analyses of the GLOBE
data including baseline prognostic factors and subgroups analysis.
Data show that the baseline tumor volume, which is a significant
prognostic factor in rGBM, was higher in the treatment arm compared
to the control arm. Overall, the subjects in the study had
relatively high tumor volume, as large-volume tumors were not an
exclusion criterion. It is of interest that patients with smaller
tumors (<15 cm3) appeared to respond better to the treatment
arm, with numerically higher response rate and overall survival
observed. Furthermore, a trend towards greater survival was
observed in patients treated with VB-111 who reported fever. VB-111
was well tolerated, with a similar early termination rate in both
the treatment and control arms. Most frequent adverse event was
self-limited fever, starting several hours post therapy and usually
resolving by 24 hours. As expected, a higher rate of SAEs and grade
>=3 AEs was reported in the combination treatment arm.
Subsequent analyses have focused on the potential reasons for
the major differences in outcomes between the positive VB-111 Phase
2 clinical trial in rGBM and the unsuccessful GLOBE results. The
Phase 2 trial of VB-111 met the primary endpoint of OS benefit with
median OS (mOS) of 13.6 months upon treatment with VB-111 as a
single drug (`priming`) followed by adding bevacizumab to VB-111
upon further progression, compared to mOS of 6.8 months for the
treatment arm in GLOBE (co-administration of VB-111 and
bevacizumab, without any VB-111 monotherapy `priming` period).
Thorough analyses of the baseline risk factors of the Phase 2
and the Phase 3 treatment groups did not reveal any differences.
Therefore, patient selection or different patient populations could
not explain the difference between the results of the two studies.
The only significant change between the Phase 2 and Phase 3
treatment cohorts was in the treatment regimen – the regimen for
Phase 2 trial included priming with VB-111 whereas the regimen for
GLOBE trial did not.
To test the hypothesis that concomitant treatment with
bevacizumab may have a negative effect on VB-111 activity, the
Company investigated this combination in a pre-clinical tumor
model. The results indicate that treatment with VB-111 in
combination with bevacizumab appears to block the anti-tumor the
effect of VB-111, compared to VB-111 monotherapy. In addition, a
retrospective analysis of a small cohort of 10 patients who were
treated concomitantly with VB-111 and bevacizumab for safety
evaluation (no priming), was inferior to what was observed with
VB-111 priming in the Phase 2 study.
To better understand these results, the Company is collaborating
with UCLA scientists in performing thorough analyses of MRI scans
for VB-111-primed combination arm patients from the Phase 2 trial,
compared to the un-primed combination arm patients in the GLOBE
trial.
“Our initial exploratory analyses demonstrate clear radiologic
responses over time in rGBM patients treated with VB-111 in the
Phase 2 trial, both on VB-111 monotherapy and in combination with
bevacizumab after priming with VB-111 alone, which were translated
to overall survival. We are currently analyzing the GLOBE MRI scans
to see if this signature of VB-111 activity is lost in the GLOBE
combination group and will report the outcome upon completion of
the analysis,” said Dr. Cloughesy.
“The new analyses we have been conducting provide insight into
how the VB-111 treatment regimen may influence its anti-tumor
effect and help us understand why the positive Phase 2 data were
not replicated in the GLOBE Phase 3 study,” said Dror Harats, M.D.,
Chief Executive Officer of VBL Therapeutics. “We believe that
priming with VB-111 without bevacizumab may be critical for the
immune and vascular-disruptive/anti-angiogenic mechanism of VB-111
in rGBM. We continue to have confidence in the ongoing OVAL Phase 3
study of VB-111 in platinum-resistant ovarian cancer patients,
whose protocol takes into account lessons learned from our GBM
trial. The OVAL Phase 3 study is evaluating VB-111 in combination
with chemotherapy rather than Avastin. The combination of VB-111
with paclitaxel worked well both in pre-clinical settings and in
our Phase 2 for ovarian cancer, including in patients whose tumors
progressed on prior treatment with Avastin. In OVAL, we are
repeating exactly the same successful Phase 2 regimen.”
For a link to the GLOBE presentation at SNO see: LINK
About the GLOBE study
The GLOBE pivotal Phase 3 trial was a randomized, controlled,
double-arm, open-label study of VB-111 dosed every two months in
combination with bevacizumab dosed every two weeks, compared to
bevacizumab monotherapy. Key inclusion criteria included first or
second progression of glioblastoma following standard of care
treatment with temozolomide and radiation, a histologically
confirmed diagnosis of glioblastoma and measurable disease by RANO
criteria at progression.
The study was conducted under a Special Protocol Assessment
(SPA) granted by the FDA, with full endorsement by the Canadian
Brain Tumor Consortium (CBTC). VB-111 has received orphan drug
designation in the United States and Europe and was granted Fast
Track designation by the FDA for promising and meaningful long-term
survival in patients with glioblastoma that has recurred following
treatment with standard chemotherapy and radiation.
About Ofranergene Obadenovec (VB-111)
VB-111, a potential first-in-class anticancer therapeutic
candidate, is the Company’s lead oncology product currently being
studied in a Phase 3 trial for ovarian cancer. VB-111 has received
orphan drug designation in both the US and Europe, and fast track
designation in the US for prolongation of survival in patients with
rGBM. In addition, VB-111 successfully demonstrated
proof-of-concept and survival benefit in Phase 2 clinical trials in
radioiodine-refractory thyroid cancer and recurrent
platinum-resistant ovarian cancer. VB-111 has received an Orphan
Designation for the treatment of ovarian cancer by the European
Medicines Agency (EMA).
About VBL
Vascular Biogenics Ltd., operating as VBL Therapeutics, is a
clinical stage biopharmaceutical company focused on the discovery,
development and commercialization of first-in-class treatments for
cancer. The Company’s lead oncology product candidate, ofranergene
obadenovec (VB-111), is a first-in-class, targeted anti-cancer
gene-therapy agent that is positioned to treat a wide range of
solid tumors. It is conveniently administered as an IV infusion
once every two months. It has been observed to be well-tolerated in
>300 cancer patients and demonstrated efficacy signals in an
“all comers” Phase 1 trial as well as in three tumor-specific Phase
2 studies. Ofranergene obadenovec is currently being studied in a
Phase 3 trial for platinum-resistant ovarian cancer.
Forward Looking Statements
This press release contains forward-looking statements. All
statements other than statements of historical fact are
forward-looking statements, which are often indicated by terms such
as “anticipate,” “believe,” “could,” “estimate,” “expect,” “goal,”
“intend,” “look forward to,” “may,” “plan,” “potential,” “predict,”
“project,” “should,” “will,” “would” and similar expressions. These
forward-looking statements include, but are not limited to,
statements regarding our programs, including VB-111, including
their clinical development, such as the timing thereof, therapeutic
potential and clinical results, and the scope and protection of our
intellectual property rights. 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, the
risk that historical clinical trial results may not be predictive
of future trial results, and that we may not realize the expected
benefits of our intellectual property protection. 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, including in our annual report
on Form 20-F for the year ended December 31, 2017, and subsequent
filings with the SEC. 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.
INVESTOR CONTACT:
Michael Rice LifeSci Advisors, LLC (646) 597-6979
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