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FDA Lifts Partial Hold on AIM2CERV Trial of Investigational Immunotherapy Agent in Cervical Cancer

Shannon Connelly
Published Online:7:56 PM, Wed May 15, 2019
The FDA has lifted the partial clinical hold placed on the phase III AIM2CERV trial (NCT02853604), which is evaluating axalimogene filolisbac (AXAL) for the treatment of patients with high-risk locally advanced cervical cancer, according to Advaxis, the developer of the investigational immunotherapy agent.

The FDA placed the partial clinical hold in January 2019, citing the need for additional information on chemistry, manufacturing, and control (CMC) matters associated with AXAL. All patients enrolled on the trial were allowed to continue receiving treatment; however, no new patients were permitted to enroll until the hold was resolved.

In its letter, the FDA acknowledged that Advaxis has now satisfactorily addressed all questions associated with the hold.

“The Advaxis team worked diligently to provide a comprehensive response back to the FDA’s requests for additional CMC information, and through constructive dialogue, we successfully resolved the partial clinical hold,” said Kenneth A. Berlin, president and CEO of Advaxis, in a statement. “Our AXAL product has demonstrated a manageable safety profile in the over 400 patients we have dosed to date, and we look forward to working with our clinical research organization to reopen enrollment at AIM2CERV sites. We remain focused on our mission of developing innovative therapies to address unmet needs and improving the lives of people with cancer.”

The double-blind, placebo-controlled, randomized phase III AIM2CERV trial (NCT02853604) is comparing outcomes with AXAL versus placebo following computer-controlled radiation therapy (CCRT) with curative intent. The primary endpoint of the study is disease-free survival (DFS), with safety, tolerability, and overall survival serving as secondary endpoints.

The trial, which is being conducted under a special protocol assessment from the FDA, has a planned enrollment of 450 patients who will be randomized 2:1 to receive placebo or 1 infusion of AXAL every 3 weeks for 3 doses for the first 3 months. This will be followed by administration of AXAL every 8 weeks for a total of 5 doses or until disease recurrence. Patients are also given a 7-day course of oral antibiotic or placebo starting at 72 hours after they complete study treatment administration.

An interim analysis is planned for when at least 50% of the number of DFS events required for full maturity of the trial are reached.

AXAL has received a fast track designation from the FDA as an adjuvant therapy for patients with high-risk locally advanced cervical cancer and has also received orphan drug designation in 3 clinical indications.

In a phase II trial evaluating AXAL for the treatment of persistent or recurrent metastatic cervical cancer, the agent showed a 12-month overall survival rate of 38% in 50 patients, which was a 52% improvement over the 12-month overall survival rate that was expected in the trial’s patient population based on prognostic factors, according to Advaxis.

The FDA previously placed a hold on a phase I/II study evaluating AXAL in combination with durvalumab (Imfinzi) in patients with advanced, recurrent, or refractory cervical cancer and human papillomavirus-associated head and neck cancer. The hold was placed in March 2018 after a report of a patient who died of acute respiratory failure following 9 months of AXAL treatment. The hold was lifted in July 2018 after Advaxis agreed to new guidelines for the early detection and treatment of rare adverse events, including acute respiratory failure.
FDA Lifts Partial Clinical Hold on Phase 3 AIM2CERV Study of Axalimogene Filolisbac [news release]. Princeton, NJ: Advaxis; May 15, 2019. https://bit.ly/2w9oeyx. Accessed May 15, 2019.

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