Background:
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.
Aim:
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.
Methods:
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.
Results:
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.
Conclusions:
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.