High-dose treatment with ADXS11-001, a Listeria monocytogenes-listeriolysin O (Lm-LLO) immunotherapy, in women with cervical cancer: a phase I, dose-escalation study


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Sharad Ghamande1,Tom Hare2,Donna Wheatley1,Lisa Hatch1,Bunja Rungruang1,John Janik1,Samir Khleif1
1Georgia Cancer Center, Augusta University,2Advaxis, Inc.

Abstract

Background

Advanced cervical cancer patients have poor prognosis, with a 5-year survival rate of 15%. ADXS11-001 is an irreversibly attenuated Lm-LLO immunotherapy secreting a human papillomavirus-E7 tumor antigen that stimulates innate and adaptive tumor-specific immunity. ADXS11-001 phase II trials have shown safety and efficacy in advanced cervical cancer patients. This study explored clinical feasibility of a higher ADXS11-001 dose than that used previously.

Method

Phase I, open-label, dose-escalation trial (NCT02164461) in women ≥18 years with persistent/metastatic/recurrent cervical squamous/adenocarcinoma not amenable to standard radiotherapy/surgery. Patients had measurable disease (RECIST v1.1) with documented progression on/intolerance to prior therapy, and ECOG PS 0–1. ADXS11-001 was administered every 3 weeks during a 12-week treatment cycle. Dose escalation followed a 3+3 design in 2 doses: 5×109 colony-forming units (CFU; Dose Level 1 [DL1]) and 1×1010 CFU (Dose Level 2 [DL2]). Primary endpoint was safety/tolerability, with the recommended phase II dose (RP2D) selected based on a dose-limiting toxicity (DLT) rate <33%; secondary endpoints included tumor response and progression-free survival.

Results

Nine of 10 enrolled patients were treated (DL1, n=6; DL2, n=3). Median age was 53 years, 78% had ECOG PS 0, and 33% underwent ≥3 prior lines of systemic therapy. Overall, 36 ADXS11-001 doses have been administered to date, including 8 at DL2. All patients experienced ≥1 adverse event (AE), with treatment-related AEs (TRAEs) reported in 8/9 patients. TRAEs occurring in ≥3 patients were chills, vomiting, hypotension, tachycardia, fever, and nausea. These were 99% grade 1–2, with 1 patient (DL1) experiencing one grade 3 DLT (hypotension), and no grade 4–5 TRAEs reported. Currently, 1 patient (DL2) remains on treatment (>9 months), with a partial response.

Conclusion

ADXS11-001 was well tolerated and the RP2D is 1×1010 CFU. Tumor response is under evaluation to assess if a higher dose may impact antitumor activity.