Advaxis,
Inc., (NASDAQ:ADXS), a leader in
developing the next generation of cancer immunotherapies, announced
today final 18-month survival data from Lm-LLO-E7-15, a
randomized Phase 2 study evaluating the safety and efficacy of ADXS-HPV
(1x109 cfu) (ADXS11-001) with and without cisplatin (40
mg/m2, weekly x5) in 110 patients with recurrent cervical cancer in two
treatment arms of 55 patients each. The primary endpoint of the study is
overall survival. These data will be presented at the 2013 Society for
Immunotherapy of Cancer (SITC) Annual Meeting in National Harbor, MD, on
November 9, 2013 (Poster #258).
The last patient last visit (Day 545) occurred on October 18, 2013. The
final 18-month survival data are 28% (31/110) which is updated from the
preliminary18-month survival of 22% (16/73) reported at the 2013 ASCO
Annual Meeting on June 2, 2013. The final 12-month survival was 36%
(39/110). These data are comparable to the results for the landmark 2004
Phase 3 study conducted by the Gynecologic Oncology Group of cisplatin
alone and cisplatin plus paclitaxel in recurrent cervical cancer
patients with the same initial performance (health) status (0-2).1
In that study, 12 month survival was presented as 35% for cisplatin
alone and 32% for the combination and 18 month survival was presented as
20% for combination therapy and 12% for cisplatin, alone.
“The final 18 month survival outcome of 28% suggests that ADXS-HPV is an
active treatment in recurrent cervical cancer. Achieving this promising
18 month survival with a single treatment cycle at the lowest effective
dose, further suggests that higher doses and repeated cycles of
immunotherapy might extend the lives of patients even further beyond the
data presented here,” commented Dr. Robert Petit, Chief Scientific
Officer of Advaxis. “To achieve this survival by giving an immunotherapy
associated with only transient and low grade side effects in advanced
cancer, supports that ADXS-HPV could provide an important new treatment
option in the management of recurrent cervical cancer.”
Median overall survival in the Advaxis study was approximately 8.5
months which is indicative of the late stage of disease and baseline
performance status of the patients. Those patients that completed the
study will continue to be followed for survival. Survival results were
not significantly different between treatment groups with or without
cisplatin chemotherapy or who had previous therapy comprised of a
combination of chemotherapy and radiation, radiation alone, or
chemotherapy alone.
The tumor response rate was 11% with 6 complete responses and 6 partial
responses/110 patients and was similar in both treatment groups per
RECIST 1.1 criteria. Stable disease >3 months was observed in 35
additional patients, for a disease control rate of 43% (47/110). Average
duration of response after 12 month minimum follow-up was 10.5 months
for both treatment groups. In those patients treated with ADXS-HPV alone
who had stable disease, the average duration of response was 6 months
compared to 4.1 months in patients treated with ADXS-HPV plus cisplatin.
Activity was observed against all high risk HPV strains detected,
including 16, 18, 31, 33, and 45.
Subset analyses showed that the combination arm (addition of cisplatin
to ADXS-HPV) did not significantly improve survival or tumor response;
and survival and tumor response were equally strong in patients with
aggressive disease (defined as recurrence ≤2 years from initial
diagnosis) versus non-aggressive disease (defined as recurrence >2 years
from initial diagnosis).
The tolerability of ADXS-HPV continues to compare favorably with single
agent and combination chemotherapies active in this disease setting. 110
patients received 264 doses of ADXS11-001 at 1x109 cfu per
dose. 42% (46/110) of patients experienced 104 mild-moderate Grade 1-2
adverse events and 2% (2/110) of patients experienced a serious adverse
event (1 Grade 3 and 1 Grade 4) related/possibly related to ADXS11-001.
This compares to published serious adverse event rates of 100%-400%
related to treatment in studies on a range of chemotherapy regimens for
cervical cancer.
Dr. Poonam Molli, Senior Scientist at Advaxis, will also present data on
initial biomarker analysis of a subset of serum samples collected from
patients in Lm-LLO-E7-15, pre- and post-dosing with ADXS11-001.
Administration of ADXS11-001 immunotherapy resulted in increased
expression of cytokines (IL6, IL-8, IL10, INF-γ and TNF-α) and
chemokines (MIP-1α, MIP-1β and MCP-1) indicating activation of innate
immunity. An association was also found between changes in the
expression of cytokine and/or other serum factors and the severity of
adverse events. These data may provide future screening tools to assist
in predicting clinical efficacy and to monitor and manage side effects.
“We are pleased with the encouraging results and fully support
continuing the path towards registration for our lead product candidate,
ADXS-HPV, in invasive cervical cancer,” added Daniel J. O’Connor, Chief
Executive Officer of Advaxis. “The completion of this study is a
considerable step in demonstrating the potential of our technology to
have a positive impact in an unmet medical need.”
These posters will be available on the Advaxis website at http://www.advaxis.com.
About The Lm-LLO-E7-15 Study
Lm-LLO-E7-15 was a randomized Phase 2 study being conducted in
India in 110 women with recurrent cervical cancer designed to evaluate
the safety and efficacy of ADXS-HPV +/- cisplatin. All patients were
treated previously with chemotherapy, radiotherapy, or both; and had an
ECOG performance status of 0-2. The ADXS-HPV treatment group received
ADXS-HPV (1x109 cfu) as 3 IV infusions 4 weeks apart, each
dose followed by antibiotic at 3 days post-dosing. The ADXS-HPV +
cisplatin treatment group received ADXS-HPV as an IV infusion (1x109
cfu), followed by antibiotic beginning 3 days post-dosing, followed 4
weeks later with 5 weekly IV administrations of cisplatin (40 mg/m2)
followed 4 weeks later by 3 IV infusions of ADXS11-001 one month apart
with antibiotic beginning 3 days after each ADXS11-001 dose. Naproxsyn
500 mg BID, (Day -1, 0) and promethazine 25 mg PO, BID (pre-dose, 8
hours) were administered as premedications. Ampicillin 500 mg QID (Days
3-9) was administered post-infusion. Safety was assessed at every visit.
Efficacy was determined from overall survival and scans taken at
baseline (before the first treatment dose) and at 3, 6, 9 12, and 18
months after treatment began.
About ADXS-HPV
ADXS-HPV is an immunotherapy that is designed to target cells expressing
the HPV gene E7. Expression of the E7 gene from high-risk HPV variants
is responsible for the transformation of infected cells into dysplastic
and malignant tissues. Eliminating these cells can eliminate the
dysplasia or malignancy. ADXS-HPV is designed to infect
antigen-presenting cells and direct them to generate a powerful,
cellular immune response to HPV E7. The resulting cytotoxic Tcells
infiltrate and attack the tumors while specifically inhibiting tumor
Tregs and MDSCs in the tumors that are protecting it.
About Cervical Cancer
According to the WHO Human Papillomavirus and Related Cancers in the
World Summary Report 2010, there are 500,000 new cases of cervical
cancer caused by HPV worldwide every year. Current preventative vaccines
cannot protect the 20 million women who are already infected with HPV;
and of the high risk oncogenic strains, only HPV 16 and 18 are present
in these vaccines. Challenges with acceptance, accessibility, and
compliance have resulted in only a third of young women being vaccinated
in the United States and even less in other countries around the world.
HPV is associated with 20-50% of oral squamous cell carcinomas.
HPV-associated head and neck cancer is growing at an epidemic rate in
western countries; and occurs more frequently (3:1) in men than women.
In the United States, the number of HPV-positive head and neck cancer
cases has already equaled the number of cases of cervical cancer and
continues to increase in frequency. HPV is associated with 80-100% of
anal cancers and is also increasing in frequency.
About Advaxis, Inc.
Advaxis is a clinical-stage biotechnology company developing the next
generation of immunotherapies for cancer. Advaxis immunotherapies are
based on a novel platform technology using live, attenuated bacteria
that are bio-engineered to secrete an antigen/adjuvant fusion protein(s)
that is designed to redirect the powerful immune response all human
beings have to the bacterium to the cancer itself.
ADXS-HPV is currently being evaluated in four clinical trials for human
papillomavirus (HPV)-associated cancers: recurrent/refractory cervical
cancer (India), locally advanced cervical cancer (GOG/NCI U.S. study,
Clinical Trials.gov Identifier NCT01266460), head & neck cancer
(CRUK study, Clinical Trials.gov Identifier NCT01598792), and anal
cancer (BrUOG study, Clinical Trials.gov Identifier NCT01671488).
Advaxis has over 15 distinct immunotherapies in various stages of
development, developed directly by Advaxis and through strategic
collaborations with recognized centers of excellence such as: the University
of Pennsylvania, the Georgia
Regents University Cancer Center, Brown
University Oncology Group, and others.
For more information please visit: www.advaxis.com
1Moore et. al. “Phase III Study of Cisplatin With or Without
Paclitaxel in Stage IVB, Recurrent, or Persistent Squamous Cell
Carcinoma of the Cervix: A Gynecologic Oncology Group Study.” Journal
of Clinical Oncology, 2004; 22:3113-3119.
Forward-Looking Statements
This news release contains forward-looking statements, including,
but not limited to: statements regarding Advaxis' development of the
next generation of cancer immunotherapies; the suggestion that ADXS-HPV
is active in invasive cervical cancer; whether higher doses and repeated
cycles of immunotherapy might further extend the lives of patients with
cervical cancer beyond the data presented here; whether ADXS-HPV could
provide an important treatment option in the management of recurrent
cervical cancer; the potential registration of ADXS-HPV, having a
positive impact in an unmet medical need. 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,
2012, which is available at http://www.sec.gov.
Advaxis undertakes no obligation to publicly release the result of any
revision to these forward-looking statements which may be made to
reflect the events or circumstances after the date hereof or to reflect
the occurrence of unanticipated events, except as required by law. You
are cautioned not to place undue reliance on any forward-looking
statements.
Copyright Business Wire 2013