Updates Presented on Cervical, Prostate and
Anal Cancer Clinical Programs
ADXS-NEO Ph 1 Trial, ADXS-HOT INDs Coming
Advaxis, Inc. (NASDAQ: ADXS), a late-stage biotechnology company
developing cancer immunotherapies, held its annual Investor &
Analyst Day this week with clinical investigators and company
leaders providing updates and details on the company’s Lm
Technology™ and nine development programs.
ADXS-PSA: Prostate Cancer Program
Mark Stein, MD, of Rutgers Cancer Institute of New Jersey,
discussed encouraging preliminary immunological data generated from
Advaxis’ prostate cancer program with ADXS-PSA in combination with
Keytruda® (pembrolizumab). Dr. Stein reported that ADXS-PSA when
used as monotherapy was shown to stabilize disease progression in
~30% (4/13) of patients in the dose escalation phase of the study.
He also reported that ADXS-PSA was shown to be able to both
activate and expand pre-existing T cell clones and was also
responsible for generation of new clones of T cells in nearly all
patients. He remarked that for patients who have stabilization of
disease, high levels of the new T cell clones persist. However, in
patients where the expanded T cell clones diminish, it leads to
disease progression.
Early data on the first few patients treated with ADXS-PSA in
combination with Keytruda suggested that the combination may lead
to the emergence of a larger number of expanded and new T cell
clones, especially over the first few treatments, thereby
increasing the frequency of expanded T cells that can persist. This
T cell clone expansion and persistence effect correlates with
stabilization of disease. These findings and additional correlative
immunologic data from this ongoing trial have been submitted for
presentation at the CRI-CIMT-EATI-AACR International Cancer
Immunotherapy Conference in Frankfurt, Germany, in September. Dr.
Stein also detailed plans to initiate an investigator sponsored
trial of ADXS-PSA in patients with earlier stage prostate
cancer.
Cervical Cancer Program Update: Axalimogene
filolisbac
Axalimogene filolisbac has received Fast Track designation for
adjuvant therapy for high-risk locally advanced cervical cancer
(HRLACC) and a Special Protocol Assessment for the global,
450-patient phase 3 AIM2CERV trial in HRLACC patients. The
immunotherapy has also received orphan drug designation in three
clinical indications.
Sharad Ghamande, MD, of the Georgia Cancer Center at Augusta
University, provided an update on axalimogene filolisbac, the
company’s lead cancer immunotherapy candidate which targets
HPV-associated cancers, including cervical cancer, and presented a
case study showing an ongoing and durable partial response seen in
a patient with recurrent metastatic disease who was heavily
pre-treated and received monotherapy with axalimogene filolisbac.
“A sustained and durable partial response is very rare for this
kind of tumor that is unresponsive to chemotherapy, and survival in
these patients is often less than 10 months,” said Dr.
Ghamande.
Metastatic Cervical Cancer Combination Study with
ADXS-DUAL
Dr. Ghamande previewed the upcoming registrational-quality study
for patients with persistent, recurrent or metastatic (squamous or
non-squamous cell) carcinoma of the cervix (PRmCC) with
Bristol-Myers Squibb’s PD-1 immune checkpoint inhibitor, Opdivo®
(nivolumab), and ADXS-DUAL, Advaxis’ next generation HPV-associated
cancer immunotherapy candidate. “ADXS-DUAL, which contains antigens
for both alpha 7 (HPV 18) and alpha 9 (HPV 16) families, has the
potential to promote more potent T-cell responses for patients with
metastatic cervical cancer where patients may have a greater
disease burden,” said Dr. Ghamande.
Focus on Patient Case Studies
The physicians in attendance shared their experiences with
patients they have personally treated with axalimogene filolisbac,
and the impact on the patients’ lives. Dr. Ghamande also shared
another case study during his presentation; a complete recovery
from the company’s GOG-0265 study. The patient was also had
recurrent metastatic disease, was heavily pre-treated and received
monotherapy with axalimogene filolisbac. Dr. Ghamande stated,
“Putting it into perspective, women with this stage of disease
rarely live more than a few months. To see these types of
responses, and to have these women not just surviving, but living
full lives, is truly stunning.”
Brian Slomovitz, MD, Director Division of Gynecologic Oncology
at the University of Miami Miller School of Medicine, shared a case
study from the company’s ongoing phase 2 study of axalimogene
filolisbac in combination with the PD-L1 blocker IMFIZI™
(durvalumab) in metastatic cervical cancer and metastatic head and
neck cancer. His 48-year-old patient, with heavily pre-treated,
recurrent cervical cancer, was enrolled in the axalimogene
filolisbac and durvalumab combination study. “She is currently 18
months out from when she started the trial and she has had a
sustained, complete remission,” said Slomovitz. “For those of us
who see cervical cancer and treat this disease, this is truly a
remarkable outcome. With only traditional therapy, it’s unlikely
this woman would be alive today.”
Axalimogene filolisbac: Anal Cancer Program
Cathy Eng, MD, FACP, of the University of Texas MD Anderson
Cancer Center, provided an update on the phase 2 FAWCETT study of
axalimogene filolisbac as a monotherapy for metastatic anal cancer.
The FAWCETT study is a multi-center, open-label, two-stage study
designed to evaluate the efficacy and safety of axalimogene
filolisbac as a monotherapy in patients with HPV-associated
metastatic anal cancer who have received at least one prior
treatment regimen for advanced disease. Dr. Eng, the principal
investigator of the study, reported that data from 29 of the
planned 31 evaluable patients enrolled in Stage 1 met the
predefined 6-month progression free survival rate, paving the way
for stage 2 of the study. Dr. Eng also noted that one patient
experienced a durable partial response lasting greater than 6
months (after progression on prior anti-PD-1 therapy). Stable
disease was reported in 7 patients (24%) and a disease control rate
of 28% was also reported. Treatment was well tolerated with mostly
grade 1-2 infusion related AEs that resolved successfully with
standard care; common (≥ 30%) treatment related AEs (TRAEs)
included grade 1-2 chills/rigors, fever, hypotension and
vomiting.
Advaxis is evaluating whether to continue to the second stage of
the monotherapy trial, or initiate a registrational-quality study
in combination with a checkpoint inhibitor in the same patient
population later this year.
European Path Towards Commercialization
Advaxis reaffirmed plans to file a complete Marketing
Authorization Application (MAA) for axalimogene filolisbac in
Europe for the treatment of metastatic cervical cancer by the end
of 2017. The European Medicines Agency (EMA) issued an Advanced
Therapy Medicinal Product (ATMP) certificate for manufacturing
quality and non-clinical data following a thorough scientific
evaluation over several months of the quality (CMC) data and
non-clinical data by the EMA’s Committee for Advanced Therapies
(CAT).
As part of the company’s overall strategy for the EU, Advaxis is
working on a comprehensive commercialization plan that will
minimize up-front costs and maximize value to shareholders. “With a
significant unmet need for cervical cancer, low vaccination and
screening rates and limited and toxic treatment options, a therapy
with the potential of axalimogene filolisbac is gaining strong
support from the European medical community,” said Chris Duke,
Advaxis Chief Operating Officer.
ADXS-HER2 Osteosarcoma Studies
Nicola Mason, PhD, BVetMed, an Associate Professor of Medicine
and Pathobiology at the University of Pennsylvania School of
Veterinary Medicine, discussed how the learnings from her work
evaluating ADXS-HER2 in dogs with surgically treated osteosarcoma
is informing the study design for a human study in pediatric
osteosarcoma. Advaxis intends to initiate a phase 2, open-label,
single-arm study of ADXS-HER2 in patients between the ages of 12
and 39 years old with HER2-expressing recurrent, completely
resected osteosarcoma. This study is being conducted in
collaboration with the Children’s Oncology Group, the world’s
largest organization devoted exclusively to childhood and
adolescent cancer research, with more than 9,000 experts in
childhood cancer at more than 200 leading children’s hospitals,
universities, and cancer centers across North America, Australia,
New Zealand, and Europe.
AXAL and Prognostic Indicators of Response
Advaxis has analyzed over 50 markers using pre- and
post-treatment samples from patients in the GOG-0265 study in a
search for potential biomarkers associated with survival benefit in
axalimogene filolisbac treatment. Four markers were found to be
highly correlated with statistical significance. Two clusters
of patients associated with positive and negative survival
outcomes were identified respectively. Upon further analysis, the
majority of the effect correlated with one particular marker,
designated as “Marker #1.” This is an important finding because
Marker #1 has not previously been associated with survival in
cervical cancer, and appears to be consistent with the axalimogene
filolisbac mechanism of action.
Marker #1 is undergoing extensive further evaluation as a
prospective biomarker indicative of response to treatment with
axalimogene filolisbac, reported Robert Petit, PhD, Advaxis Chief
Scientific Officer. The 12-month survival rate in GOG-0265 patients
with “low” levels of Marker #1 was 49%, compared to 0% in the
patients who were Marker #1 high (N=10/50, 20%) with no differences
in other prognostic factors. “If we excluded “Marker #1 high”
patients and adjust the 12-month survival rate in the GOG-0265
patient population, then the 12-month survival rate would increase
to almost 50 percent,” said Dr. Petit. “We look forward to further
study of Marker #1 and anticipate prospectively stratifying
patients in future studies to meet the regulatory standard to
validate it as a biomarker.”
The company plans to present this data at the International
Meeting of the European Society of Gynecological Oncology (ESGO) in
Vienna, Austria, in November.
Emerging Opportunities: ADXS-NEO, ADXS-HOT and Lm-WT1
The company confirmed that it is on track to initiate clinical
studies of ADXS-NEO later this year. ADXS-NEO is a personalized
neoantigen-targeted approach to cancer immunotherapy that is being
developed in collaboration with Amgen for the treatment of several
metastatic tumor types. This approach also uses Lm technology, and
the FDA accepted the ADXS-NEO IND in March 2017. This is an
important milestone, as the NEO IND is one of the first INDs for a
patient-specific neoantigen treatment. Once in clinic, the Advaxis
turnaround time from biopsy to infusion is expected to take 6-8
weeks.
Building on the learnings from ADXS-NEO, the company confirmed
plans to file two new Investigational New Drug applications with
the U.S. Food and Drug Agency (FDA) in the second half of this year
for ADXS-HOT. ADXS-HOT leverages Advaxis’ Lm Technology to target
public or shared acquired mutations, so-called “hotspots,” in tumor
driver genes. Advaxis has developed a library of constructs
targeting hotspots that could be available to patients following a
rapid diagnostic test that does not require sequencing.
Advaxis is collaborating with SELLAS Life Sciences to use Lm
technology and SELLAS’ patented WT1 targeted heteroclitic peptide
antigen. The WT1 antigen is highly expressed in most tumor types
and considered the most important cancer antigen by the National
Cancer Institute.
About Advaxis, Inc.
Located in Princeton, N.J., Advaxis, Inc. is a late-stage
biotechnology company developing multiple cancer immunotherapies
based on its proprietary Lm Technology. Lm Technology,
using bioengineered live attenuated Listeria
monocytogenes (Lm) bacteria, is the only known cancer
immunotherapy agent shown in preclinical studies to both generate
cancer fighting T cells directed against cancer antigens and
neutralize Tregs and myeloid-derived suppressor cells (MDSCs) that
protect the tumor microenvironment from immunologic attack and
contribute to tumor growth. Advaxis’ lead Lm Technology™
immunotherapies axalimogene filolisbac and ADXS-DUAL target
HPV-associated cancers and are in clinical trials for four
potential indications, including phase 3 in invasive cervical
cancer and metastatic cervical cancer in combination with
nivolumab, phase 2 in head and neck cancer, and phase 2 in anal
cancer. The FDA has granted axalimogene filolisbac orphan drug
designation for each of these three clinical settings, as well as
Fast Track designation for adjuvant therapy for HRLACC patients and
a SPA for the phase 3 AIM2CERV trial in HRLACC patients.
Axalimogene filolisbac has also been classified as an advanced
therapy medicinal product for the treatment of cervical cancer by
the EMA’s CAT. Advaxis has two additional immunotherapy products:
ADXS-PSA in prostate cancer and ADXS-HER2 in HER2 expressing solid
tumors, in human clinical development. In addition, Advaxis and
Amgen are developing ADXS-NEO, an investigational cancer
immunotherapy treatment designed to activate a patient's immune
system to respond against the unique mutations, or neoepitopes,
contained in and identified from each individual patient's tumor,
with plans to enter the clinic in 2017.
To learn more about Advaxis, visit www.advaxis.com and connect
on Twitter, LinkedIn, Facebook, and YouTube.
Advaxis Forward-Looking Statement
This press release contains forward-looking statements,
including, but not limited to, statements regarding Advaxis’
ability to develop the next generation of cancer immunotherapies,
and the safety and efficacy of Advaxis’ proprietary
immunotherapies, axalimogene filolisbac and ADXS-DUAL. These
forward-looking statements are subject to a number of risks
including the risk factors set forth from time to time in Advaxis’
SEC filings including, but not limited to, its report on Form 10-K
for the fiscal year ended October 31, 2016, which is available at
http://www.sec.gov.
Any forward-looking statements set forth in this presentation
speak only as of the date of this presentation. We do not intend to
update any of these forward-looking statements to reflect events or
circumstances that occur after the date hereof other than as
required by law.
You are cautioned not to place undue reliance on any
forward-looking statements.
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version on businesswire.com: http://www.businesswire.com/news/home/20170613006195/en/
Company:Advaxis, Inc.Noelle Heber, 609-250-7575Sr.
Director Corporate Communications and Government
Affairsheber@advaxis.comorMedia Contact:JPA Health
CommunicationsDavid Connolly, 617-657-1301dconnolly@jpa.com
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