Kenneth A. Berlin
The FDA has placed a partial clinical hold on the phase III AIM2CERV trial (NCT02853604) evaluating the use of axalimogene filolisbac (AXAL) in patients with high-risk locally advanced cervical cancer, according to Advaxis, Inc., the developer of the investigational immunotherapy agent.1
The communication from the FDA cites that the partial hold has been put in place until additional information on chemistry, manufacturing, and control (CMC) matters associated with AXAL, are received. No safety issues associated with the trial were cited, and all participants currently enrolled will continue to receive treatment with the agent. However, no new patients can enroll in the trial until the hold is resolved.
“The FDA’s review of the AXAL Investigational New Drug application was prompted by our proposal to modify the AIM2CERV trial’s analysis plan to include, among other things, allowance for a second formal interim analysis for both safety and efficacy,” said Kenneth A. Berlin, president and chief executive officer of Advaxis, in a press release. “The primary focus of the items raised by the agency relates to providing additional clarifying details for CMC information previously provided in support of phase III development and which will help support a future Biologics License Application.”
Berlin adds that Advaxis representatives have already taken steps to provide the FDA with the requested information on AXAL in an effort to get the hold lifted in a timely manner.
Treatment for patients with high-risk locally advanced cervical cancer following concurrent chemotherapy and radiation therapy is an area of significant unmet need in the space. In an effort to address this need, investigators launched the double-blind, placebo-controlled, randomized phase III trial to compare disease-free survival (DFS) outcomes of AXAL with placebo following computer-controlled radiation therapy (CCRT) with curative intent.2
In the trial, patients are randomized 2:1 to receive placebo or 1 infusion of AXAL every 3 weeks for 3 doses for the first 3 months. This is followed by administration of AXAL every 8 weeks for a total of 5 doses or until disease recurrence. Patients are then given a 7-day course of oral antibiotic or placebo starting at 72 hours after they complete the study treatment.
The current study design has a planned sample size of 450 participants in order to maintain adequate statistical power over a broader range of survival outcomes. Investigators will perform an interim analysis when at least 50% of the number of DFS events required for full maturity of the trial are reached.
“AIM2CERV is a global trial with almost 150 sites in more than 20 countries. We take the patients who are destined to fail, meaning patients with either advanced cervical cancer or patients with early disease who have positive lymph nodes,” said Sharad Ghamande, MD, an associate professor at the Georgia Cancer Center, Augusta University, in a prior interview with OncLive
. “These patients finish their radiation and chemotherapy, and once they are in remission, they are randomized 2:1 to either the vaccine for up to 1 year or a placebo. It is a registrational trial that will hopefully make a difference in these patients’ lives by preventing cervical cancer.”
The FDA previously lifted a clinical hold in July 2018 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 initiated in March 2018 following a report of a patient who died of acute respiratory failure following 9 months of AXAL treatment. Following the hold, Advaxis had agreed to new guidelines for the early detection and treatment of rare adverse events, acute respiratory failure.
“Our AXAL product has demonstrated a manageable safety profile in the over 400 patients we have dosed to date and we look forward to enrolling new patients in our AIM2CERV trial after the FDA agrees that the information that we submit is responsive to its requests,” concluded Berlin.
- Advaxis’ Phase 3 AIM2CERV Study Placed on Partial Clinical Hold by FDA Related to CMC Requests [news release]. Advaxis; January 23, 2019. https://bit.ly/2S3GMNa. Accessed January 24, 2019.
- Study of ADXS11-001 in Subjects With High Risk Locally Advanced Cervical Cancer (AIM2CERV). ClinicalTrials.gov website. clinicaltrials.gov/ct2/show/NCT02853604?term=NCT02853604. Published August 3, 2016. Updated April 12, 2018. Accessed January 24, 2019.