- Updated data from Phase 1/2 ADXS-PSA
study combination arm show prolonged survival in heavily pretreated
prostate cancer patients with microsatellite-stable (MSS)
disease
- Updated early findings from Phase 1
ADXS-NEO study show encouraging safety, immunogenicity and clinical
signals in MSS colorectal cancer patients
Advaxis, Inc. (NASDAQ: ADXS), a late-stage
biotechnology company focused on the discovery, development and
commercialization of immunotherapy products, announces the
presentation of two posters at the Frontiers in Cancer
Immunotherapy conference, being held today at the New York Academy
of Sciences in New York City. Both posters were first presented at
the recent American Association for Cancer Research (AACR) Annual
Meeting, and each has updated findings being presented today.
The first presentation regarding a poster entitled “Effects of
ADXS-PSA With or Without Pembrolizumab on Survival and Antigen
Spreading in Metastatic, Castration-Resistant Prostate Cancer
Patients (Results from KEYNOTE-046)” is conference poster #31, and
will be presented by Robert Petit, Ph.D., Advaxis Chief Scientific
Officer, and Mark N. Stein, M.D., FACS, Associate Professor of
Medical Oncology at Columbia University Medical Center, from 4:45
to 5:30 p.m. Eastern time.
The Phase 1/2 KEYNOTE-046 study is being conducted in
conjunction with Merck (known as MSD outside the U.S. and Canada)
in metastatic, castration-resistant prostate cancer (mCRPC). This
trial and is evaluating ADXS-PSA, one of Advaxis’ Listeria
monocytogenes (Lm)-based immunotherapies, alone and in combination
with KEYTRUDA® (pembrolizumab), Merck’s anti-PD-1 therapy.
KEYNOTE-046 is an open-label, multicenter, dose-determining
safety and tolerability Phase 1/2 trial of 50 heavily pretreated
patients conducted in two parts (Part A and Part B), with a Phase 2
expansion cohort. The objective of the study is to evaluate
ADXS-PSA alone (Part A) and in combination with KEYTRUDA® (Part B)
for primary endpoints that include safety, tolerability and dosing.
Secondary endpoints include anti-tumor activity and
progression-free survival, and exploratory endpoints include
associations between biomarkers of immunologic response (serum PSA)
with clinical outcomes.
Key findings from 37 patients treated in the combination arm
(Part B) of KEYNOTE-046 as reported at AACR include the
following:
- The majority of treatment-related
adverse events consisted of transient and reversible Grade 1-2
chills/rigors, fever, hypotension, nausea and fatigue. The
combination of ADXS-PSA and pembrolizumab has been well-tolerated
to date, with no additive toxicity observed.
- Median overall survival (OS) was 21.1
months at data cutoff (February 1, 2019) (95% CI, range 16.0 months
to not-yet-reached) in this dataset of 37 patients.
- Correlative immune analyses showed
T-cell responses against PSA in 75% of subjects and antigen
spreading in 85% of subjects.
- Broader immune stimulation, including
B-cell activation, was observed in the combination arm (n=37) than
in the ADXS-PSA monotherapy arm (n=13).
Updated findings being presented at the Frontiers in Cancer
Immunotherapy conference include:
- Microsatellite Instability-High
(MSI-High), the condition of genetic hypermutability that results
from defective DNA mismatch repair, is observed in 5-12% of all
mCRPC patients and often leads to a higher likelihood of response
to immunotherapy. In this study, 36 of the patients in the
combination arm, which observed prolonged survival, were MSI-High
negative (with one subject not tested), thereby making them
unlikely to respond to checkpoint blockade.
- There are 16 patients in the
combination therapy part of this trial who are alive and continue
to be monitored.
“The latest results from our KEYNOTE-046 study demonstrate that
practically all the patients in the combination arm of this study
are microsatellite stable and therefore are not expected to respond
to treatment with a checkpoint inhibitor,” said Kenneth A. Berlin,
President and Chief Executive Officer of Advaxis. “These data
suggest that the combination of ADXS-PSA and pembrolizumab appears
to show activity and to be associated with prolonged OS in this
population.”
The second poster discussion entitled “Safety and Immunogenicity
of a Personalized Neoantigen-Listeria Vaccine in Cancer Patients”
is conference poster #9, and will be presented by Frank Tsai, M.D.,
Medical Oncologist and Investigator at Honor Health Research
Institute and one of the lead investigators of the ADXS-NEO
clinical study, from 4:45 to 5:30 p.m. Eastern time.
ADXS-NEO is a live, attenuated Lm immunotherapy using
personalized antigen delivery based on whole-exome sequencing of a
patient’s tumor to identify personal neoantigens. The ongoing Phase
1 trial is designed to evaluate the safety, tolerability and
preliminary clinical immunological activity of ADXS-NEO alone (Part
A) and in combination with anti-PD-1 antibody therapy (Part B) in
subjects with certain types of advanced or metastatic solid tumors.
Part C of the trial will be an expansion of the combination therapy
arm and will be initiated based on emerging data from the first two
parts of the trial.
Preliminary findings from the ADXS-NEO Phase 1 study as reported
at AACR include the following:
- Substantial anti-tumor immunity,
including T cell responses to neoantigens and antigen spreading,
was observed within one week of first dose at both dose
levels.
- Dosing of ADXS-NEO at 1x108 colony
forming units (CFU) has been well-tolerated in two
patients.
- ADXS-NEO dosed at 1x109 CFU was beyond
the maximum tolerated dose (MTD)
- Reversible Grade 3 hypoxia (n=2) and
Grade 3 hypotension (n=1) were dose-limiting toxicities
(DLTs).
- Manufacturing of ADXS-NEO, comprised of
40 personal neoantigens, was successfully completed within seven to
eight weeks for each subject.
Updated findings being presented at the Frontiers in Cancer
Immunotherapy conference include:
- Data from the two MSS colorectal cancer
patients dosed with ADXS-NEO at 1x108 CFU demonstrated
increased CD8+ T cell infiltration in the tumor microenvironment
after three doses of ADXS-NEO. Both patients had metastatic
colorectal cancer, which is considered to be a “cold” tumor and
typically exhibits little CD8+ T cell infiltration and resistance
to immunotherapy, yet both successfully transitioned from “cold”
tumors into “hot” tumors with ADXS-NEO therapy. An estimated 80-85%
of colorectal cancer patients are MSS.
- Two patients (one treated at 1x109 and
one at 1x108 CFU) achieved stable disease per RECIST 1.1 criteria.
Another patient has yet to be evaluated but has experienced normal
performance status and an active lifestyle over the three months of
therapy with ADXS-NEO at 1x108 CFU.
“Although we have just started to define the safety,
immunogenicity and changes in the tumor microenvironment with
ADXS-NEO monotherapy, it is possible that these effects may have a
positive impact in the sensitivity to checkpoint inhibitors in
‘cold’ tumors,” said Dr. Tsai. “We look forward to further
documenting the effects of ADXS-NEO monotherapy in MSS metastatic
colorectal cancer (CRC) and in other tumors. Also, since the
majority of patients with MSS-CRC do not respond well to
immunotherapy, we are also looking forward to starting the
combination therapy of ADXS-NEO and a checkpoint inhibitor, as
called for in the current study.”
Mr. Berlin added, “We are pleased to report encouraging updated
findings from both of these ongoing studies at the Frontiers in
Cancer Immunotherapy conference. We are encouraged given that we
are seeing clinical benefit from our immunotherapy drug candidates
in difficult-to-treat patient populations in furtherance of our
mission to helping improve the lives of people with cancer. We look
forward to sharing further data from our programs throughout the
balance of the year.”
Both posters will be available at www.advaxis.com today at 4:45
p.m. ET.
About KEYNOTE-046
KEYNOTE-046 (NCT02325557) is a Phase 1/2 open-label,
multicenter, dose-determination and expansion trial that evaluates
the safety, tolerability and preliminary clinical activity of
ADXS-PSA as monotherapy (Part A; n=14 [13 treated]), and in
combination with KEYTRUDA® (Part B; n=37) in heavily pretreated
patients with progressive and refractory mCRPC.
About ADXS-PSA
ADXS-PSA, one of Advaxis' Lm-based immunotherapies, utilizes
live, attenuated, bioengineered Lm as a vector to deliver PSA
directly to antigen presenting cells. Development is being
pursued in a clinical trial collaboration and supply agreement with
Merck.
About ADXS-NEO
ADXS-NEO is an investigational personalized Lm-based
immunotherapy designed to generate immune response against
mutation-derived tumor-specific neoantigens identified through DNA
sequencing of a patient’s own tumor. The program focuses on
creating a customized treatment for each patient targeting multiple
neoantigens found in a biopsy of the patient’s tumor.
About Advaxis, Inc.
Advaxis, Inc. is a late-stage biotechnology company focused on
the discovery, development and commercialization of
proprietary Lm-based antigen delivery products. These
immunotherapies are based on a platform technology that utilizes
live attenuated Listeria monocytogenes (Lm) bioengineered to
secrete antigen/adjuvant fusion proteins. These Lm-based
strains are believed to be a significant advancement in
immunotherapy as they integrate multiple functions into a single
immunotherapy and are designed to access and direct antigen
presenting cells to stimulate anti-tumor T cell immunity, activate
the immune system with the equivalent of multiple adjuvants, and
simultaneously reduce tumor protection in the tumor
microenvironment to enable T cells to eliminate tumors. Advaxis has
four programs in various stages of clinical development: ADXS-HPV
for cervical cancer; ADXS-NEO, a personalized neoantigen-directed
therapy for multiple cancers; ADXS-503 for non-small cell lung
cancer, from its ADXS-HOT off-the-shelf neoantigen-directed
program; and ADXS-PSA for prostate cancer.
To learn more about Advaxis, visit www.advaxis.com and connect
on Twitter, LinkedIn, Facebook and YouTube.
Advaxis Forward-Looking Statement
Some of the statements included in this press release may be
forward-looking statements that involve a number of risks and
uncertainties. For those statements, we claim the protection of the
safe harbor for forward-looking statements contained in the Private
Securities Litigation Reform Act of 1995. The factors that could
cause our actual results to differ materially include: the success
and timing of our clinical trials, including subject accrual; our
ability to avoid any clinical holds and to resolve FDA’s partial
clinical hold; our ability to obtain and maintain regulatory
approval and/or reimbursement of our product candidates for
marketing; our ability to obtain the appropriate labeling of our
products under any regulatory approval; our plans to develop and
commercialize our products; the successful development and
implementation of our sales and marketing campaigns; the size and
growth of the potential markets for our product candidates and our
ability to serve those markets; our ability to successfully compete
in the potential markets for our product candidates, if
commercialized; regulatory developments in the United States and
other countries; the rate and degree of market acceptance of any of
our product candidates; new products, product candidates or new
uses for existing products or technologies introduced or announced
by our competitors and the timing of these introductions or
announcements; market conditions in the pharmaceutical and
biotechnology sectors; our available cash; the accuracy of our
estimates regarding expenses, future revenues, capital requirements
and needs for additional financing; our ability to obtain
additional funding; our ability to obtain and maintain intellectual
property protection for our product candidates; the success and
timing of our preclinical studies including IND-enabling studies;
the timing of our IND submissions; our ability to get FDA approval
for study amendments; the timing of data read-outs; the ability of
our product candidates to successfully perform in clinical trials;
our ability to initiate, enroll, and execute pilots and clinical
trials; our ability to maintain collaborations; our ability to
manufacture and the performance of third-party manufacturers; the
performance of our clinical research organizations, clinical trial
sponsors and clinical trial investigators; our ability to
successfully implement our strategy; and, other risk factors
identified from time to time in our reports filed with
the SEC. Any forward-looking statements set forth in this
press release speak only as of the date of this press release. We
do not intend to update any of these forward-looking statements to
reflect events or circumstances that occur after the date
hereof.
KEYTRUDA® is a registered trademark of Merck Sharp & Dohme
Corp., a subsidiary of Merck & Co., Inc., Kenilworth, N.J.,
USA.
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Investors:LHA Investor RelationsYvonne Briggs, (310)
691-7100ybriggs@lhai.com
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