Advaxis, Inc., a clinical stage biotechnology company developing cancer immunotherapies, announced that it reached an agreement with the US Food and Drug Administration (FDA), under the Special Protocol Assessment (SPA) process, for the phase 3 AIM2CERV trial evaluating the company’s lead Lm immunotherapy candidate, axalimogene filolisbac (AXAL), in patients with high-risk, locally advanced cervical cancer (HRLACC). AIM2CERV is a multinational, randomized, controlled clinical trial conducted in collaboration with The GOG Foundation, Inc. Trial enrollment will commence this summer.

A successfully concluded SPA provides a binding agreement with FDA’s review division that a pivotal trial design, conduct, and planned analysis adequately address the scientific and regulatory objectives in support of a regulatory submission for drug approval. Final marketing approval depends upon the efficacy results, safety profile and an evaluation of the risk/benefit of treatment demonstrated in the phase 3 clinical trial.

In the 10-year period ending in 2013, only 25 per cent of the requests for a SPA of oncology trials concluded with an FDA agreement.

“Receiving a SPA for the AIM2CERV trial is a testament to the promising AXAL results we have seen in cervical cancer patients,” said Bradley Monk, M.D., Professor and director of the Division of Gynecologic Oncology at Creighton University School of Medicine at St. Joseph’s Hospital and Medical Center and lead cervical cancer advisor to Advaxis. “The AIM2CERV trial will be a critical step in demonstrating that AXAL can be successful as an immunotherapy, with the trial’s goal to cure more women, and prevent disease recurrence.”

“Collaborative discussions with the FDA led to a positive outcome with a SPA that clearly defines the clinical and regulatory pathway for the approval and commercialization of AXAL for the treatment of patients with HRLACC,” said Daniel J. O’Connor, president and chief executive officer. “Obtaining a SPA for the AIM2CERV phase 3 protocol was our number one priority this year and it has now been achieved.”

AXAL is a live attenuated Listeria monocytogenes bacteria bioengineered to target HPV-associated cancer. The primary objective of AIM2CERV is to compare the disease free survival of AXAL to placebo administered in the adjuvant setting following concurrent chemotherapy and radiotherapy (CCRT) administered with curative intent to patients with HRLACC. Secondary endpoints include examining overall survival and safety.

A SPA is an agreement with the FDA that the proposed trial protocol design, clinical endpoints and statistical analyses are acceptable to support the submission of an application for FDA’s determination of regulatory approval.

Cervical cancer is the third most common malignancy in women worldwide. In the United States, nearly 13,000 new cases are diagnosed, and approximately 4,100 deaths are reported due to cervical cancer. According to the WHO/ICO Information Centre on HPV and Cervical Cancer, about 3.9 per cent of women in the United States are estimated to harbor high-risk cervical HPV infection at a given time, and 71.7 per cent of invasive cervical cancers are attributed to high-risk HPV strains.

Axalimogene filolisbac (AXAL) is Advaxis' lead Lm Technology immunotherapy candidate for the treatment of patients with HPV-associated cancers and is in clinical trials for three potential indications: invasive cervical cancer, head and neck cancer, and anal cancer. In a completed randomized phase 2 study in recurrent/refractory cervical cancer, AXAL showed apparent prolonged survival, objective tumor responses, and a manageable safety profile alone or in combination with chemotherapy, supporting further development of the company’s Lm Technology. AXAL has Orphan Drug designation in the US for the treatment of anal cancer.