Advax is Inc., the live, attenuated Listeria monocytogenes (Listeria) immunotherapy company has begun dosing patients in its 110 patient clinical trial of ADXS11-001 for the treatment of cervix cancer in women for whom cytotoxic treatment has failed. This follows extensive review by the office of the Drugs Controller General of India (DCGI), a blue ribbon commission of scientists convened to assess Advaxis clinical protocol, and a chemical and microbiological assessment of ADXS11-001 by the Indian Central Vaccine Research Laboratory at Kasuli. The initial patient is at the Dr. Kamakshi Memorial Hospital in Chennai.
The US National Cancer Institute’s Gynaecologic Oncology Group has conducted 16 clinical trials in over 500 patients using various therapeutic regimens in this patient population and found the most effective regimen tested resulted in a median survival of approximately 6 months and a 1 year survival of 5%. By contrast, in a phase 1 study not designed to show efficacy, ADXS11-001 demonstrate a median survival of 347 days and a one year survival of 53%.
Because of the progressive and rapidly fatal nature of cervix cancer in women for whom cytotoxic treatment has failed, the design of this trial allows for a rapid appraisal of efficacy. Advaxis intends to report the effect of ADXS11-001 on survival versus these historical values in “real time”, as the trial progresses, beginning in summer, 2011.
This trial differs from Advaxis phase I trial in this patient population in two significant ways. First, the phase II will assess the more therapeutic regimen of three doses compared with two in phase I. Second, this randomized trial compares ADXS11-001 alone with ADXS11-001 combined with platinum based chemotherapy. Combined immuno and chemo-therapy regimens may be more effective than single agent regimens, and Advaxis has generated some anecdotal data in support of this idea in the phase I trial.
Patients will be randomly assigned to receive either three administrations of ADXS11-001 (55 patients) or a single dose of the immunotherapy, followed by cisplatin treatment, followed by a three course regimen of ADXS11-001 (55 patients). Various clinical and immunologic measures will be taken and survival will be followed for the life of the patient.
ADXS11-001 is a live, attenuated Listeria vaccine that targets the Human Papilloma Virus (HPV) oncoprotein E7. HPV is recognized as the cause of cervix cancer and E7 is one of the HPV proteins believed to be responsible. Doses of 1x109, 3.3x109 or 1x1010 cfu were administered to groups of five women who had failed prior therapy including radiation and chemotherapy. In such cases, no therapy has been found to be effective and the median survival once disease progression resumes is typically six months or less, depending upon the treatment given. One year survival for these patients historically is approximately 5%.
The phase I trial of ADXS11-001 was intended to assess safety. Like all phase-I trials, it was not powered for efficacy; so, no conclusions can be made based upon the small number of patients treated. However, in this trial, the median survival was 347 days and the 1 year survival was 53%.
Advaxis is a biotechnology company developing proprietary, live, attenuated Listeria monocytogenes (Listeria) vaccines that deliver engineered tumour antigens, which stimulate multiple, simultaneous immunological mechanisms to fight cancer. Today, the Company has nine distinct, cancer-fighting constructs in various stages of development, directly and through strategic collaborations with such recognized sites of excellence as the City of Hope, the Roswell Park Cancer Institute, the National Cancer Institute, the University of Pittsburgh, Cancer Research – UK and the Department of Homeland Security. Advaxis’ technology was developed by Dr. Yvonne Paterson, professor of microbiology at the University of Pennsylvania and chairperson of Advaxis’ scientific advisory board.