PRINCETON, N.J.--(BUSINESS WIRE)--Advaxis, Inc., (OTCBB: ADXS), a leader in developing the next generation of immunotherapies for cancer and infectious diseases, announced today final 12 month overall survival and additional data from Lm-LLO-E7-15, a randomized Phase 2 study evaluating the safety and efficacy of ADXS-HPV +/- cisplatin in patients with recurrent cervical cancer. The data were presented by Dr. Robert Petit, Chief Scientific Officer at Advaxis, at the 2013 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, IL, on Sunday, June 2, 2013 (Abstract #5529).
As of May 17, 2013, the trial has completed enrollment and 110 patients have received 264 doses of ADXS-HPV (ADXS11-001). Final 12 month overall survival is 36% (39/110) with a (current) 18 month survival of 22% (16/73). This compares to 33% and 17%, respectively, at the last update and are the best results yet reported for this study.
These data are comparable to the results for the landmark 2004 Moore Phase 3 study 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.
Median overall survival was approximately 8.5 months. Those patients who have completed the study will continue to be followed for survival. Survival results were not significantly different between groups who had previous therapy of radiation, alone, chemotherapy, alone, or a combination of both.
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 33 additional patients, for a disease control rate of 41% (45/110). 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 human papillomavirus (HPV) strains detected, including 16, 18, 31, 33, and 45.
Subset analyses showed that the addition of cisplatin to ADXS-HPV did not significantly improve survival or tumor response in this study; 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. 41% (45/110) of patients experienced 104 mild-moderate Grade 1-2 adverse events and 2% (2/110) of patients experienced a Grade 3 serious adverse event. This compares to published treatment-related serious adverse event rates of 100%-400% in studies evaluating a range of chemotherapy regimens for cervical cancer, including the Moore study and studies conducted by the Gynecologic Oncology Group (GOG) of the National Cancer Institute (NCI).
“These data suggest that ADXS-HPV has the potential to become a non-chemotherapy treatment option capable of improving survival for women with cervical cancer. Clinical benefit was evident in this trial even in women with cancer that recurred aggressively, who had bulky metastatic tumors, and who had been previously treated with both chemotherapy and radiotherapy. The side effects reported by less than half of the patients were mild, and associated primarily with the infusion. Furthermore, the ability of ADXS-HPV in this study to cause durable complete and partial remission of solid tumors as a monotherapy, is very promising,” commented Dr. Petit.
Thomas A. Moore, Chairman and CEO of Advaxis, further commented, “These results have stood up very well, both over time and in our new, detailed analysis. We believe the promising clinical benefits and attractive side effect profile shown in the data collected about ADXS-HPV thus far make this potentially a whole new class of therapy in this disease. Advaxis will progress ADXS-HPV to registrational trials as quickly as possible, exploring additional dosing that may further extend any clinical benefits.”
The poster will be available on the Advaxis website at http://www.advaxis.com.
About The Lm-LLO-E7-15 Study
Lm-LLO-E7-15 is 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 1 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 is assessed at every visit. Efficacy is 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 begins.
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 and infectious diseases. 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 being evaluated in four clinical trials for HPV-associated diseases: 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). 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 National Cancer Institute, Cancer Research – UK, the Wistar Institute, the University of Pennsylvania, the University of British Columbia, the Karolinska Institutet, and others. For more information please visit: advaxis.com | Facebook | twitter | LinkedIn
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: follow-up for survival for patients who have completed the study, the ability of ADXS-HPV to become a non-chemotherapy treatment option capable of improving survival for women with cervical cancer, the ability of ADXS-HPV to cause durable complete and partial remission of solid tumors as a monotherapy, the potency of ADXS-HPV, the potential for a whole new class of therapy for cervical cancer, the progression of ADXS-HPV to registrational trials, and exploring additional dosing for ADXS-HPV. These forward-looking statements are subject to a number of risks, such as 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 www.sec.gov. The Company 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.
