Advaxis has acknowledged that the FDA has placed on clinical hold its Phase I/II cancer combination treatment study assessing its axalimogene filolisbac (ADXS11-001) with AstraZeneca’s Imfinzi® (durvalumab), following the death of a patient last month.

The combination study is designed to assess the axalimogene filolisbac/Imfinzi combo in patients with advanced, recurrent, or refractory human papillomavirus (HPV)-associated cervical cancer and HPV-associated head and neck cancer. Following the trial’s sixth combination cycle, a patient developed respiratory failure and died, Advaxis disclosed yesterday.

“Over the course of the treatment cycle, this patient received 11 doses of AXAL and 21 doses of durvalumab. It should be noted that over 250 patients have received AXAL and approximately 700 doses have been delivered across multiple trials in HPV-associated cancers to-date and that this is the first time we have seen this type of event,” Advaxis interim CEO Anthony Lombardo told analysts yesterday on the company’s quarterly conference call following release of results for the first quarter of its 2018 fiscal year ending January 31, according to a transcript published by Seeking Alpha.

A safety report on the patient death or “Grade 5 Serious Adverse Event” was submitted to the FDA on February 27, Advaxis stated.

“Enrollment and further dosing are on hold in this trial while the company, its partner, and the FDA work closely with the site investigator to review this event in detail and to resolve this clinical hold,” the company said.

Axalimogene filolisbac is Advaxis’ lead candidate among the company’s immunotherapies, which are based on a platform technology that uses live attenuated Listeria monocytogenes (Lm) bioengineered to secrete antigen/adjuvant fusion proteins.

The clinical hold has no effect on enrollment and dosing in any of Advaxis’ other clinical programs, the company added.

“We are confident in the safety and efficacy profile of axalimogene filolisbac to date,” Lombardo said in a company statement. “We care deeply for our patients and for their safety as we work to research and develop new treatment options for advanced cancers. We believe in the potential of our Lm technology to provide new advancements in the area of cancer care.”

Advaxis tucked its disclosure of the clinical hold within its announcement of results from its fiscal first quarter of 2018, made yesterday after the close of the financial markets.

HPV-associated cancers like the ones under study in the clinical trial are one of Advaxis’ four therapeutic “franchises” or specialties. The other three are neoantigen therapy, hotspot/cancer antigens, and prostate cancer.

Seeking Approval in PRmCC

On February 13, Advaxis announced that it had submitted a conditional Marketing Authorization Application to the European Medicines Agency for axalimogene filolisbac, for the treatment of adult women who progress beyond first-line therapy of persistent, recurrent, or metastatic carcinoma of the cervix (PRmCC). Advaxis cited improvement in the primary efficacy endpoint of the Phase II GOG-0265 study, which showed a 12-month overall survival (OS) rate of 38% (19 of 50) women with PRmCC, representing a 55% improvement over an expected, model-predicted, 12-month survival rate of 24.5%. 

A day earlier, Advaxis announced publication of positive overall survival data from another Phase II study comparing axalimogene filolisbac as a monotherapy with axalimogene filolisbac in combination with chemotherapy (cisplatin) in 110 patients with PRmCC. That study showed a 12-month OS rate of approximately 35% (38 of 109 participants), as well as a median OS of 8.28 months in the axalimogene filolisbac monotherapy arm and 8.78 months in the combination arm.

According to Advaxis, Lm-based strains are designed to integrate multiple functions into a single immunotherapy, as well as to access and direct antigen-presenting cells to stimulate antitumor T-cell immunity, activate the immune system with the equivalent of multiple adjuvants, and simultaneously reduce tumor protection in the tumor microenvironment to enable the T cells to eliminate tumors.

Imfinzi is a programmed death-ligand 1 (PD-L1)-blocking antibody approved last month for the additional indication of unresectable stage III non-small-cell lung cancer (NSCLC) in patients whose disease has not progressed following concurrent platinum-based chemotherapy and radiation therapy (CRT).

Last year, AstraZeneca won accelerated approval from the FDA for Imfinzi in its initial indication, locally advanced or metastatic urothelial carcinoma in patients who have disease progression during or following platinum-containing chemotherapy, or whose disease has progressed within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.


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