FDA Halts Combo Trial of Axalimogene Filolisbac Plus Durvalumab


The FDA has put a clinical hold on a phase I/II study of axalimogene filolisbac plus durvalumab (Imfinzi) for the treatment of patients with cervical cancer or head and neck cancer.

Anthony Lombardo

The FDA has put a clinical hold on a phase I/II study of axalimogene filolisbac (AXAL) plus durvalumab (Imfinzi) for the treatment of patients with advanced, recurrent or refractory HPV-associated cervical cancer and HPV-associated head and neck squamous cell carcinoma (HNSCC).

Axalimogene filolisbac is a targeted Listeria monocytogenes (Lm)-based immunotherapy that attacks HPV-associated cancers. The FDA cited a safety report regarding a patient who died February 27, 2018, of respiratory failure following the sixth combination cycle in the trial. Advaxis, the manufacturer of axalimogene filolisbac, announced the hold in a quarterly earnings report.

"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," Anthony Lombardo, interim Advaxis CEO, said in a statement. "We are confident in the safety and efficacy profile of axalimogene filolisbac, to date, based on our experience in over 250 patients and over 700 doses across multiple trials in HPV-associated cancers."

Enrollment and dosing in all other Advaxis clinical programs are unaffected.

Preliminary results from the phase I/II study put on hold (NCT02291055) were presented at the 2016 Society for Immunotherapy of Cancer (SITC) Annual Meeting.1 At the time of the data presentation, 11 patients enrolled in phase I of the 2-stage study. Most patients (91%) had an ECOG performance status of 0. Seventy-three percent of patients had recurrent or metastatic cervical cancer, 75% of whom had received prior bevacizumab (Avastin). The remainder of patients had metastatic HPV+ HNSCC.

One patient with cervical cancer achieved a complete response, which remained ongoing after 12 months of follow-up. Another patient with cervical cancer achieved a partial response with subsequent disease progression.

Two patients with HNSCC had stable disease. Treatment-related adverse events (TRAE) were reported in 91% of patients, though most were either grade 1/2 events such as chills, fever, nausea and hypotension. Three patients experienced grade 3 TRAEs, and 1 patient experienced a grade 4 event.

There were no dose-limiting toxicities observed, and phase I established the recommended phase II dose at 1 × 109 CFU for axalimogene filolisbac and 10 mg/kg for durvalumab.

Results from the phase II GOG 0265 trial presented last year at the Society of Gynecologic Oncology Annual Meeting also demonstrated the activity of axalimogene filolisbac in metastatic cervical cancer. The 1-year OS was 38% in 50 patients receiving axalimogene filolisbac. At the time, researchers said that result was as good if not better than the best outcomes reported with currently available therapies, and represented a 52% improvement versus the logistic model-predicted milestone survival rate of 24.5%.

Investigators in GOG 0265 enrolled 63 patients in 2 stages. All patients had received at least 1 prior line of systemic therapy for recurrent/persistent metastatic cervical cancer beyond primary curative treatment.

The first stage of the trial included 27 patients. If axalimogene filolisbac induced a 15% absolute improvement in the benchmark 1-year survival of 20%, later refined to 24.5%, the trial would proceed to the second stage. After that goal was met, investigators enrolled an additional 36 patients. The coprimary endpoints were 12-month OS and safety and tolerability.

Just over half of patients had received 2 or more prior lines of therapy, 28 had exposure to bevacizumab, and 43 had received pelvic radiation therapy.

The median OS was 6.2 months, with a 12-month survival of 38% (P = .02). One patient achieved a complete response with axalimogene filolisbac and 15 had stable disease.

HPV genotyping for 41 patients showed that 35 tested positive for the virus, including 33 evaluable patients, 16 who tested positive for HPV-16 and 17 who were positive for HPV-18. The HPV-16-positive subgroup had a 12-month survival of 44% and median OS of 17.8 months for those patients alive at 12 months. The HPV-18-positive subgroup had a 12-month OS of 41% and median OS of 15.7 months among those alive at 12 months.


  1. Slomovitz BM. A phase I/II study of durvalumab alone or in combination with AXAL in recurrent/persistent or metastatic cervical or human papillomavirus (HPV)+ squamous cell cancer of the head and neck (SCCHN): preliminary phase I results. Presented at: 2016 SITC Annual Meeting; November 9-13, 2016; National Harbor, MD. Abstract 248.
  2. Huha W, Brady WE, Dizonc DS, et al. A prospective phase II trial of the listeria-based human papillomavirus immunotherapy axalimogene filolisbac in second- and third-line metastatic cervical cancer: A NRG oncology group trial. Presented at: 2017 SGO Annual Meeting; March 12-15, 2017; National Harbor, MD. Abstract LB3.
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