Advaxis, Inc., a clinical-stage biotechnology company developing cancer immunotherapies, and MedImmune, the global biologics R&D arm of AstraZeneca, announced that enrollment has commenced in a phase I/II clinical trial of axalimogene filolisbac (ADXS-HPV), Advaxis's investigational Lm Technology immunotherapy, in combination with MedImmune's investigational anti-PD-L1 immune checkpoint inhibitor, durvalumab (MEDI4736), for the treatment of patients with advanced, recurrent or refractory human papillomavirus (HPV)-associated cervical cancer and HPV-associated head and neck cancer.

The two-part, open-label phase I/II study is designed to evaluate the safety and efficacy of axalimogene filolisbac as a monotherapy and in combination with durvalumab in approximately 66 patients. Phase I is a dose-confirmation combination study with axalimogene filolisbac and durvalumab, which is expected to establish the maximum tolerated dose. The phase II portion of the study will randomize patients to receive axalimogene filolisbac monotherapy, durvalumab monotherapy, or the combination. The primary efficacy endpoints include objective response rate and progression-free survival.

"We are pleased to have initiated patient enrollment for this combination immunotherapy study and look forward to evaluating this immunotherapy combination in the clinic, with the hopes of confirming the preclinical anti-tumour effects," said Daniel J. O'Connor, president and CEO of Advaxis.

"The initiation of our combination immunotherapy study with MedImmune adds to what has become a rapidly expanding clinical development pipeline for Advaxis involving our Lm Technology immunotherapy platform alone and in combination with potentially synergistic technologies."

Axalimogene filolisbac and durvalumab are members of a new class of cancer treatments known as immunotherapies, which are designed to enhance the body's own defenses in fighting cancer. Data from preclinical studies suggest that Advaxis's Lm Technology immunotherapies in combination with a checkpoint inhibitor, such as durvalumab, may lead to an enhanced anti-tumor immune response. Results from the phase I/II study will determine the future clinical development programme for the combination.

Cervical cancer is the fourth most common cancer and the most common cause of mortality in women worldwide with 528,000 new cases reported annually and an estimated 266,000 deaths in 2012; the majority of which is diagnosed in less-developed countries. Within the US, approximately 12,900 cases of invasive cervical cancer are diagnosed annually and up to 30 per cent are diagnosed with locally advanced disease. Despite a well-established and adopted standard of care for the treatment of locally advanced cervical cancer, consisting of cisplatin and radiotherapy administered concurrently, a large percentage of these patients, particularly those with high risk features and/or poor prognostic factors, will experience cancer recurrence and ultimately die of their disease. These patients represent a subpopulation of locally advanced cervical cancer with the highest unmet medical need and where the need for new therapeutic options is greatest as there are no approved therapies for this specific patient population.

The incidence of HPV-associated head and neck cancers has been increasing at an epidemic rate, while head and neck cancers from other causes have been decreasing. According to the WHO, approximately 15-20 per cent of the 400,000 new cases of head and neck cancer are HPV-related. In the US, there are about 12,000 new cases of HPV-associated head and neck cancer per year, affecting men about three times more frequently than women. HPV-associated head and neck cancer is growing fastest in developed countries like the US.

Axalimogene filolisbac is Advaxis's lead Lm Technology immunotherapy candidate for the treatment of 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 II study in recurrent/refractory cervical cancer, axalimogene filolisbac showed apparent prolonged survival, objective tumour responses, and a manageable safety profile alone or in combination with chemotherapy, supporting further development of the company's Lm Technology.

Durvalumab is an investigational human monoclonal antibody directed against programmed cell death ligand 1 (PD-L1). Signals from PD-L1 help tumours avoid detection by the immune system. Durvalumab blocks these signals, countering the tumor's immune-evading tactics.

Durvalumab was accelerated into phase III clinical development in non-small cell lung cancer and head and neck cancer. The OCEANS clinical development programme will evaluate durvalumab as monotherapy and in combination with a cytotoxic T-lymphocyte-associated protein-4 (CTLA-4) monoclonal antibody tremelimumab, in lung cancer, across the spectrum of the disease. In head and neck cancer, durvalumab is being investigated in three late stage studies (HAWK, CONDOR and EAGLE) as monotherapy and in combination with tremelimumab, looking at patients with different PD-L1 expression status who have failed on chemotherapy.

A comprehensive development programme for durvalumab is underway across multiple tumour types, including gastric, pancreatic and bladder cancer, in addition to lung and head and neck cancers.