A phase III trial testing the ability of Advaxis Inc.’s lead immunotherapy candidate, axalimogene filolisbac, to improve disease-free survival among patients with high-risk locally advanced cervical cancer has enrolled and dosed its first patient. The FDA fast-tracked study, called AIM2CERV, is expected to enroll 450 patients and is being run under a special protocol assessment.

The global, randomized trial gives Advaxis its first shot at potentially getting a product on the market and a stable foothold in cervical cancer, an area to which big pharma has paid less attention since the introduction of human papillomavirus (HPV) vaccines have reduced the incidence of vaccine-type HPV and the associated incidence of HPV-related diseases like cervical cancer.

The primary objective of the trial, agreed to with the FDA, is to compare disease-free survival (DFS) in patients receiving axalimogene filolisbac, or Axal, to DFS in patients receiving placebo. It’s an endpoint supported by GOG Foundation Inc., a nonprofit that has collaborated with the company on trial design, and appropriate for several reasons, Advaxis President and CEO Dan O’Connor told BioWorld Today.

As a monotherapy focused on preventing cervical cancer recurrence in patients who had no evidence of the disease after chemotherapy and radiation, he said, the goal is to prevent micro-metastatic disease not observable by conventional imaging techniques from gaining traction.

“If we can put these patients in a position where their disease doesn’t recur at all or significantly extend the time to recurrence, the clinicians that treat the patients day in, day out feel that that’s a tremendous advancement,” he said.

Secondary objectives of the trial include overall survival, safety and tolerability.

A second phase III study of Axal in metastatic cervical cancer is planned for initiation in the second half of the year. That trial, which would enroll women with persistent or recurrent metastatic (squamous or nonsquamous cell) carcinoma of the cervix (PRmCC), is intended to build on top-line data from the phase II GOG-0265 study presented by Advaxis last year. The GOG-0265 study showed a 12-month overall survival rate of 38 percent in 50 patients with PRmCC, a 52 percent improvement over the 12-month overall survival rate expected in the trial’s patient population based on prognostic factors.

The most commonly reported side effects during the ‘0265 study were hypotension and symptoms related to cytokine release, including nausea, chills and fever. Full data from the study will be presented at the Society of Gynecologic Oncology’s 48th Annual Meeting on Women’s Cancer in March.

Axal received orphan drug and fast track status for adjuvant therapy in high-risk locally advanced carcinoma of the cervix and FDA orphan drug designation for stage II-IV cervical cancer. It has also been classified as an advanced therapy medicinal product for the treatment of cervical cancer by the EMA. The company plans to submit a European marketing authorization application for approval of Axal to treat patients with metastatic cervical cancer in the second half of 2017.

Princeton, N.J.-based Advaxis has raised about $260 million in the last few years, following a reverse stock split in August 2013 that helped it prepare for its up-listing to Nasdaq that year.

Progress continues on the company’s development of the preclinical cancer immunotherapy, ADXS-NEO, for which it licensed global rights to Amgen Inc. for a combined pledge of up to $540 million in August 2016. Advaxis expects to submit an investigational new drug (IND) application to the FDA for the program sometime early this year. (See BioWorld Today, Aug. 3, 2016.)

The company is also planning to complete initial dosing of part B of its phase I/II trial evaluating ADXS-PSA in combination with Keytruda (pembrolizumab) in advanced, metastatic castration-resistant prostate cancer and present preliminary data at a medical meeting in 2017.

Preparations are also underway for filing an IND with the FDA for ADXS-HOT constructs that target tumor driver genes, “hotspot” mutations or public mutations found in various cancer types, expected in the second half of this year.