ADXS11-001 immunotherapy targeting HPV-E7: Preliminary survival data from a P2 study in Indian women with recurrent/refractory cervical cancer.

Abstract

5529 Background: ADXS11-001 immunotherapy is a live attenuated Listeria monocytogenes (Lm) bioengineered to secrete a HPV16-E7 fusion protein targeting HPV transformed cells. The Lm vector serves as its own adjuvant and infects APC where it naturally cross presents, stimulating both MHC class 1 and 2 pathways resulting in specific T-cell immunity to tumors. Here we describe the preliminary survival data associated with ADXS11-001 administration in Lm-LLO-E7-015, a randomized P2 study being conducted in India in 110 patients with recurrent/refractory cervical cancer who have been treated previously with chemotherapy, radiotherapy or both. Methods: Patients were randomized to either 3 doses of ADXS11-001 at 1 x 109 cfu or 4 doses of ADXS11-001 at 1 x 109cfu with cisplatin chemotherapy. Naprosyn and oral promethazine were given as premedications and a course of ampicillin was given 72h after infusion. Patients received CT scans at baseline and 3, 6, 9, 12 and 18 months. The primary endpoint is overall survival. Results: As of February 2013, the trial has completed enrollment and 110 patients have received 264 doses of ADXS11-001. The percentage of patients alive at 6 months is 63% (67/107); at 9 months is 46% (49/106); at 12 months is 34% (30/87) and at 18 months is 15% (8/54). Tumor responses have been observed in both treatment arms with 6 CRs and 6 PRs; 36 additional patients had stable disease > 3 months, for a disease control rate of 44% (48/110). Activity against different high risk HPV strains has been observed. Three serious adverse events and 69 mild-moderate adverse events possibly related/related to ADXS11-001 treatment have been reported in 41% (45/110) of patients. The non-serious adverse events consisted predominately of transient, non-cumulative flu-like symptoms associated with infusion that either resolved on their own or responded to symptomatic treatment. Conclusions: ADXS11-001 can be safely administered to patients with advanced cancer alone and in combination with chemotherapy. ADXS11-001 is well tolerated and presents a predictable and manageable safety profile. Final 12-month OS, updated safety and translational analyses will be presented at the meeting.