ADXS11-001 immunotherapy is a live attenuated Listeria monocytogenes (Lm) bioengineered to secrete HPV-16-E7 fusion protein targeting HPV transformed cells. The Lm-vector stimulates MHC class 1 and 2 pathways resulting in specific T-cell immunity to tumors.
A randomized phase-II study designed to evaluate the safety and efficacy of ADXS11-001 with and without cisplatin in patients with recurrent cervical cancer was conducted in India from November 2010 to July 2013. The final results are presented here.
Recurrent cervical cancer patients (N=110) treated earlier by radiotherapy and/or chemotherapy were randomized to receive either 3 doses of ADXS11-001 at 1 x 109 cfu alone or 4 doses of ADXS11-001 at 1 x 109 cfu with cisplatin (40mg/m2). 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 was overall survival.
The final 18-month survival was 22% (24/109) and 12 month survival was 32% (35/109). The response rate was 11% (5 CRs and 6 PRs/110) with tumor responses observed in both treatment arms; 31 additional patients had stable disease >3 months, for a disease control rate of 38% (42/110). Average duration of response in both treatment groups was ~9.5 months. The incidence of SAEs possibly related or related to ADXS11-001 was 2%. The majority of non-serious adverse events were predominately infusion associated, and either resolved on their own or responded to symptomatic treatment.
The 22% 18-month survival, 32% 12-month survival and 11% response-rate observed in recurrent disease setting is encouraging and suggests that ADXS11-001 is an active agent in cervical cancer. Baseline performance-status, type of prior therapy, aggressiveness of disease or addition of cisplatin to ADXS11-001 had no effect on survival outcomes or tumour responses.