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ADXS11-001 LM-LLO Immunotherapy Targeting HPV-E7: Preliminary Safety and Survival Data From a Phase 2 Study in Indian Women With Recurrent/Refractory Cervical Cancer

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Abstract

ADXS11-001 immunotherapy is a live attenuated Listeria monocytogenes (Lm) bioengineered to secrete a HPV-16-E7 fusion protein targeting HPV transformed cells. The Lm vector serves as its own adjuvant and infects antigen presenting cells (APC) where it cross presents, stimulating MHC class I and II pathways resulting in specific T-cell immunity to tumors. Here we describe final 12 month overall survival data associated with ADXS11-001 administration in Lm-LLO-E7-015, a randomized P2 study conducted in India in 110 patients with recurrent cervical cancer; previously treated with chemotherapy, radiotherapy or both. Patients were randomized to either 1 cycle (3 doses) of ADXS11-001 at 1 x 109 cfu or 4 doses of ADXS11-001 at 1 x 109 cfu with cisplatin chemotherapy. Naprosyn and oral promethazine were given as premedications and a course of ampicillin was given 72 hours after infusion. Patients received CT scans at baseline and 3, 6, 9, 12 and 18 months. The primary endpoint is overall survival. As of May 17, 2013, the trial has completed enrollment and 110 patients received 264 doses of ADXS11-001. The percentage of patients at 12 months is 36% (39/110) and currently the 18 month survival is 22% (16/73). The response rate was 11% (6 CRs and 6 PR/110) with tumor responses observed in both treatment arms. 33 additional patients had stable disease > 3 months, for a disease control rate of 41% (45/110). Activity was observed against all high risk HPV strains detected. Two Grade 3 serious adverse events and 104 mild-moderate adverse events possibly related/related to ADXS11-001 treatment have been reported in 41% (45/110) of patients. The non-serious adverse events consisted predominately of transient, non-cumulative flu-like symptoms associated with infusion that either self-resolved or responded to symptomatic treatment. ADXS11-001 can be safely administered to patients with advanced cancer alone and in combination with chemotherapy. ADXS11-001 is well tolerated and presents a predictable and manageable safety profile. The addition of cisplatin to ADXS11-001 in this study did not significantly improve tumor responses or overall survival. Objective tumor responses included CR’s and apparent prolonged survival with minimal adverse experiences. Average duration of response in both treatment groups was 10.5 months. The 36% 12 month survival and 11% response rate observed in this recurrent disease setting is encouraging and suggests that ADXS11-001 is an active agent in recurrent cervical cancer. Final 18 month overall survival will be presented at the meeting.
P O STER P RESENTATION Open Access
ADXS11-001 immunotherapy targeting HPV-E7:
updated survival and safety data from a phase
2 study in Indian women with recurrent/refractory
cervical cancer
Robert G Petit
1*
, Partha Basu
2
From Society for Immunotherapy of Cancer 28th Annual Meeting
National Harbor, MD, USA. 8-10 November 2013
ADXS11-001 immunotherapy is a live attenuated Listeria
monocytogenes (Lm) bioengineered to secrete a HPV-16-
E7 fusion protein targeting HPV transformed cells. The
Lm vector serves as its own adjuvant and infects antigen
presenting cells (APC) where it cross presents, stimulat-
ing MHC class I and II pathways resulting in specific
T-cell immunity to tumors. Here we describe final
12 month ov era ll s urvi val data associated with ADXS11-
001 administ ration in Lm-L LO-E7- 015, a randomized P2
study conduct ed in India in 110 pat ients with recurrent
cervical cancer; previously treate d w ith c hemotherapy,
radiotherapy or both. Patients were randomized to either
1cycle(3doses)ofADXS11-001at1x10
9
cfu or 4
dosesofADXS11-001at1x10
9
cfuwithcisplatinche-
motherapy. Naprosyn and oral promethazine were given
as premedications and a course of ampicillin was given
72 hours after infusion. Patients received CT scans at
baseline and 3, 6, 9, 12 and 18 months. The primary end-
point is overall survival. As of May 17, 2013 , the trial has
completed enrollment and 110 patients received 264
doses of ADXS11-001. The percentage of patients at
12 months is 36% (39/110) and currently the 18 month
survival is 22% (16/73). The response rate was 11%
(6 CRs and 6 PR/110) with tumor responses observed in
both treatment arms. 33 additional patients had stable
disease > 3 months, for a disease control rate of 41%
(45/110). Activity was observed against all high risk HPV
strains detected. Two Grade 3 serious adverse events and
104 mild-moderate adverse events possibly related/
related to ADXS11-001 treatment have been reported in
41% (45/110) of patients. The non-serious adv erse events
consisted predominately of transient, non-cumulative flu-
like symptoms associated with infusion that eithe r s elf-
resolved or responded to symptomatic treatment.
ADXS11-001 can be safely admi nist ered to patien ts with
advanced cancer alone and in combination with che-
motherapy. ADXS11-001 is well tolerated and presents a
predictable and manageable safety profile. The addition
of cisplatin to ADXS11-001 in this study did not signifi-
cantly improve tumor responses or overall survival.
Objective t umor responses included CR s a nd apparent
prolonged survival with minimal adverse experiences.
Average duration of response in both treatment groups
was 10.5 mon ths. The 36% 12 month survival and 11%
response rate observed in this recurrent disease setting is
encouraging and suggests that ADXS11-001 is an active
agent in recurrent cervical cancer. Final 18 month overall
survival will be presented at the meeting.
Authors details
1
Advaxis, Inc., Princeton, NJ, USA.
2
Chittaranjan National Cancer Institute,
Kolkata, India.
Published: 7 November 2013
doi:10.1186/2051-1426-1-S1-P231
Cite this article as: Petit and Basu: ADXS11-001 immunotherapy
targeting HPV-E7: updated survival and safety data from a phase
2 study in Indian women with recurrent/refractory cervical cancer.
Journal for ImmunoTherapy of Cancer 2013 1(Suppl 1):P231.
1
Advaxis, Inc., Princeton, NJ, USA
Full list of author information is available at the end of the article
Petit and Basu Journal for ImmunoTherapy of Cancer 2013, 1(Suppl 1):P231
http://www.immunotherapyofcancer.org/content/1/S1/P231
© 2 013 Petit and Basu; licensee BioMed Central Ltd. This is a n Open Access article distributed under the terms of the Creative
Commons Attribution License (http://creativecommons.org/lice nses/by/2.0), which permits unrestricted use, distribution, and
reproduction in any medium, provided the original work is properly cited.
... It is worth mentioning that Advaxis, a clinical-stage biotechnology company, has made a major breakthrough in Lm immunotherapy technology. Among them, the ADXS11-001 vaccine, a live attenuated Lm bacterium bioengineered to secrete the HPV-16 E7 protein fused with a truncated fragment of listeriolysin O (tLLO), has been used in the treatment of anal and cervical cancer and has conducted clinical trials [8,9]. In addition, the ADXS31-142 (secretion of LLO and human prostate specific antigen) and ADXS31-164 (secretion of chimeric tLLO fusion protein containing immunogenic regions of HER2 protein) vaccines were used to treat prostate and breast cancer, respectively [10,11]. ...
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... The safety of LM vaccine has been well-demonstrated in human clinical trials: Angelakopoulos's clinical trial demonstrated the ability of an attenuated LM-based empty vaccine to safely and effectively induce antigen-specific T cell responses in humans (Angelakopoulos et al., 2002); Maciag's Phase I trial and Petit's Phase II clinical trial with LM-LLO-E7 verified that the safe and effective recombinant vaccines could be potentially a new therapeutic option (Maciag et al., 2009;Petit and Basu, 2013). LM has particular advantages to offer as a neonatal vaccine vehicle: attenuated strains of LM that are safe for neonates have now been identified, and interestingly, they are very efficient at inducing robust Th1-type immunity in neonates (Kollmann et al., 2007). ...
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