AXAL Clinical Program

Advaxis’ lead Lm Technology™ immunotherapy, axalimogene filolisbac, or AXAL, targets HPV-associated cancers and is in clinical trials for three potential indications: invasive cervical cancer, head and neck cancer, and anal cancer. The U.S. Food and Drug Administration (FDA) has granted AXAL orphan drug designation in each of these three clinical settings, as well as a Special Protocol Assessment for the Phase 3 AIM2CERV trial in cervical cancer, and Fast Track Designation. AXAL is currently being evaluated in eight clinical trials for HPV-associated cancers. Please visit www.ClinicalTrials.gov for more information on Advaxis clinical trials.

Cervical Cancer

AXAL has shown promising anti-tumor activity and acceptable tolerability across several clinical trials. Advaxis has reached an agreement on a Special Protocol Assessment (SPA) with the U.S. Food and Drug Administration (FDA) in June 2016 for the Phase 3 AIM2CERV study, evaluating the safety and efficacy of AXAL administered in the adjuvant setting after completion of cisplatin-based chemotherapy and radiotherapy in patients with locally advanced cervical cancer at higher risk for recurrence, progression, or death. The study plans to enroll approximately 450 patients, with the first patient to be enrolled in the third quarter of 2016. The Phase 3 trial will be conducted in collaboration with the GOG Foundation, Inc, now part of NRG Oncology. AXAL also received Fast Track Designation from the FDA as an adjuvant therapy for HRLACC patients and was classified as an advanced-therapy medicinal product by the European Medicines Agency’s Committee for Advanced Therapies for the treatment of cervical cancer.

Advaxis has completed a randomized Phase 2 clinical trial of AXAL with or without cisplatin chemotherapy in Indian patients with persistent or recurrent metastatic (squamous or non-squamous cell) carcinoma of the cervix (PRmCC). Results from the trial demonstrated promising activity (12-month overall survival rate of 32 percent) and acceptable tolerability, with chills and flu-like symptoms the most common treatment-related adverse events.

Advaxis is currently collaborating with the GOG on an ongoing two-stage Phase 2 study, GOG-0265, of AXAL in patients with PRmCC who had progressed on at least one prior line of systemic therapy. Clinical data from Stage 1 showed treatment with AXAL resulted in a 38.5 percent 12-month overall survival rate in 26 patients. Stage 2, which was amended to allow increased dosing, involved a more heavily bevacizumab pre-treated population and demonstrated a 42 percent six-month overall survival rate, and a 67 percent six-month survival rate in 12 patients who received three or more doses of AXAL. The 12-month overall survival data had not yet matured at the last analysis.

AXAL is being evaluated in three additional ongoing clinical trials in HPV-associated cervical cancer, either alone at higher doses than those utilized to date or in combination with other immunotherapeutics, such as MedImmune’s durvalumab (MEDI4736).

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Head and Neck Cancer

AXAL is under evaluation in two clinical trials for HPV-associated head and neck cancer. The first is a “window of opportunity” Phase 2 study, conducted by the Icahn School of Medicine at Mount Sinai, investigating the effects of AXAL in patients newly diagnosed with HPV-positive head and neck cancer during the window of time between initial diagnosis and receiving any treatment, including surgery, chemotherapy or radiation. As of April 2016, the trial enrolled eight AXAL-treated patients and six no-treatment observational patients with stage II-IV HPVOPC. Clinical data showed increased T-cell response in several patients, evidence of epitope spreading, and signs of increased immune activation consistent with expansion and infiltration of activated T cells into the tumor.

The second is a Phase 1/2 study evaluating the safety and efficacy of AXAL alone or in combination with MedImmune’s investigational anti-PD-L1 immune checkpoint inhibitor, durvalumab (MEDI4736), for the treatment of patients with advanced, recurrent or refractory cervical cancer and HPV-associated head and neck cancer. The first and second dose-escalation cohort in the trial has been completed, and the Companies have commenced enrollment for the Part A expansion and Part B of the study.

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Anal Cancer

Advaxis has collaborated with Brown University Oncology Group on a Phase 1/2 clinical study assessing the safety and efficacy of AXAL administered with concurrent standard chemotherapy and radiation treatment in HPV-associated locally advanced anal cancer. Preliminary data show clinical complete response and no recurrence in all 10 patients who completed the AXAL-containing treatment regimen.

In June 2016, Advaxis began dose administration for a Phase 2 clinical study of AXAL in metastatic anal cancer. The study is called FAWCETT (Fighting Anal Cancer with CTL-Enhancing Tumor Therapy), in honor of Farrah Fawcett, and is the company’s second Phase 2 study of AXAL in anal cancer. The two-part, multi-center, open-label study is designed to evaluate the efficacy and safety of AXAL as a monotherapy in patients with HPV-associated metastatic anal cancer who have received at least one prior treatment regimen for advanced disease.

Advaxis has also entered into a clinical trial collaboration agreement with the Radiation Therapy Oncology Group (RTOG) Foundation to evaluate the safety and efficacy of ADXS-HPV in a pivotal Phase 2/3 anal cancer trial, which will be run by NRG Oncology.

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HPV as a Therapeutic Target

There are 528,000 new cases of cervical cancer reported annually worldwide, and an estimated 266,000 related deaths.1 In the U.S., 12,900 cases are diagnosed per year, with 30 percent detected in the locally advanced or metastatic stages.2,3

Cervical cancer is largely the result of persistent infection with high-risk types of human papilloma virus (HPV). In fact, HPV DNA is present in the majority of cervical cancer. AXAL is a live attenuated Listeria monocytogenes (Lm) bioengineered to secrete an HPV-16 E7 protein fused with a truncated fragment of listeriolysin O (tLLO). AXAL targets HPV transformed cells, inducing antitumor T-cell immunity and breaking immune tolerance in the tumor microenvironment. AXAL has the potential to fill a significant unmet need in the treatment of advanced cervical cancer.

References

1 Ferlay J, S.I., Ervik M, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray, F., GLOBOCAN 2012 v1.0, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 11 [Internet]. Lyon, France: International Agency for Research on Cancer; 2013. Retreived June 12, 2015 from http://globocan.iarc.fr.

2 American Cancer Society. Cancer Facts & Figures 2015. Atlanta: American Cancer Society; 2015.

3 Monk, B.J., K.S. Tewari, and W.J. Koh, Multimodality therapy for locally advanced cervical carcinoma: state of the art and future directions. J Clin Oncol, 2007. 25(20): p. 2952-65.