Elenagen, a p62/SQSTM1-encoding plasmid, improves overall survival in patients with platinum-resistant ovarian cancer: a phase II trial

Abstract

Objective: Platinum-resistant ovarian cancer remains a major therapeutic challenge, with limited benefit from currently available cytotoxic agents. Elenagen is a newly developed plasmid DNA-based anti-cancer agent that encodes p62/SQSTM1 protein, a multi-functional adapter protein involved in selective autophagy, signal transduction, and modulation of the inflammatory response. We previously reported the progression-free survival outcomes of patients with platinum-resistant ovarian cancer treated with Elenagen. We report the overall survival results from a phase II randomized controlled trial comparing Elenagen plus gemcitabine with gemcitabine alone.

Methods: This open-label, prospective, randomized, 2-center study enrolled women with platinum-resistant ovarian cancer. Patients were randomly assigned (1:1) to receive gemcitabine monotherapy (1000 mg/m² on days 1 and 8 every 21 days) or gemcitabine plus Elenagen (2.5 mg intra-muscularly weekly). The primary end point was overall survival; secondary end points included safety, post-progression outcomes, and time-dependent analyses of Elenagen exposure. Survival was analyzed using Kaplan-Meier and Cox proportional hazards models.

Results: Thirty patients (15 per arm) were evaluable for overall survival. Baseline demographic and clinical characteristics were balanced between groups. Among patients with elevated CA-125 levels (> 35 U/mL), median overall survival was 13 months (95% confidence interval [CI] 10 to 27) in the gemcitabine arm and 25 months (95% CI 17 to not reached) in the Elenagen plus gemcitabine arm (log-rank p = .031). Treatment with Elenagen was associated with a 59% reduction in the risk of death (hazard ratio 0.41, 95% CI 0.18 to 0.94, p = .036). Time-dependent and landmark analyses demonstrated a positive association between longer Elenagen exposure and improved survival (p < .001). No additional safety signals were observed compared with gemcitabine alone. Post-progression survival and subsequent therapy patterns were comparable between arms.

Conclusions: The addition of Elenagen to gemcitabine prolonged overall survival in patients with platinum-resistant ovarian cancer without increasing toxicity.

Trial registration: NCT05979298, 2023-08-07.

Keywords: Elenagen; Gemcitabine; Plasmid Therapy; Platinum-Resistant Ovarian Cancer; p62/SQSTM1.