37. ADXS11-001, mitomycin, 5-FU and radiation for anal cancera A phase I/II study.

Background Human papillomavirus (HPV) DNA is present in the majority of squamous cell cancers of the anus. ADXS11-001 immunotherapy is a live attenuated Listeria monocytogenes (Lm) bioengineered to secrete an HPV-16-E7 fusion protein targeting HPV-transformed cells. The Lm vector infects antigen-presenting cells, stimulating both MHC class 1 and 2 pathways resulting in specific T-cell immunity to tumours. The Brown University Oncology Research Group has initiated a phase I/II study evaluating two treatment schedules of ADXS11-001 with standard chemoradiation for anal cancer. Methods: Patients with newly diagnosed anal cancer with a primary tumour >4cm or lymph node involvement, without distant metastases, are eligible. All patients receive two courses of mitomycin, 5-FU with concurrent radiation (54Gy in 30 fractions by IMRT). Patients receive four treatments of ADXS11-001, 1×10(9) colony-forming units intravenously once approximately every 28 days. In treatment schedule 1, the first dose is given before chemoradiation and the second to fourth doses are given every 28 days after completion of radiation. In treatment schedule 2, the second dose of ADXS11-001 is administered during chemoradiation. Results: Three patients have been treated with ADXS11-001 and chemoradiation on treatment schedule 1. One patient developed grade 3 chills and one patient experienced grade 2 flu-like symptoms post-infusion, both resolved with symptomatic treatment. Conclusions: ADXS11-001 is a highly novel form of immunotherapy designed to generate an immune response against HPV transformed cells. Accrual is continuing to evaluate safety and efficacy for patients with anal cancer.