Elenagen/Gemacitabine Combo Shows Efficacy, Safety in Ovarian Cancer

Results from a phase 2 trial (NCT05979298) demonstrated that elenagen plus gemacitabine significantly improved overall survival (OS) in patients with platinum-resistant ovarian cancer (PROC) with elevated baseline CA-125 levels (>35 U/mL).^1,2

The data cut-off occurred 56 months after the trial began. The addition of elenagen resulted in a statistically significant survival advantage. In the elenagen arm (n = 15), median OS was 25 months (95% CI, 17-not reached). In the gemacitabine arm (n = 15), the median OS was 13 months (95% CI, 10-27). Approximately 25% of patients in the elenagen cohort survived beyond 48 months.

The strongest association with survival was observed during the first 12 months of therapy. Landmark analysis suggests that treatment beyond 18 to 24 months may not provide significant additional OS benefits.

Safety and Post-Progression Observations

The study reported no additional safety signals or increased toxicity compared with gemcitabine alone.

Patients were permitted to transition to alternative chemotherapy upon progression. Common subsequent treatments included taxanes and irinotecan. Patterns and lines of subsequent therapy were comparable between both arms, suggesting the survival benefit was due to elenagen rather than differential post progression care. Elenagen treatment was maintained beyond progression per protocol, as its immunomodulatory mechanisms remain relevant even as the disease advances.

Mechanism of Action of Elenagen

Elenagen is a proprietary plasmid DNA-based agent encoding the human p62 (SQSTM1) protein. Its therapeutic action is driven by several pathways:

• Protein function: p62 is a multi-functional adapter protein involved in selective autophagy, signal transduction, and modulation of inflammatory responses.
• NF-κB inhibition: Elenagen can inactivate NF-κB signaling, which is typically associated with poor prognosis and the development of chemo- and immune resistance in ovarian cancer.
• Anti-inflammatory effects: Preclinical studies indicate systemic anti-inflammatory activity, including the reduction of pro-inflammatory cytokines (IL-1b, IL-6, TNF) and the elevation of anti-inflammatory cytokines.
• Chemo sensitization: It is hypothesized that elenagen prevents the feed-forward loop where gemcitabine activates NF-κB, thereby sensitizing cancer cells to the chemotherapy.

Phase 2 Trial Methodology and Design

The study was an open-label, prospective, randomized, 2-center trial conducted in Belarus between January 2020 and August 2024.

A total of 30 patients with baseline CA-125 >35 U/mL were evaluable for the primary analysis. The baseline characteristics (age, histology, grade, and previous lines of therapy) were well-balanced between the 2 groups. Patients were between the ages of 18 and 70. Patients in the control arm received 1000 mg/m² of gemcitabine on days 1 and 8 of a 21-day cycle. Patients in the elenagen arm received a standard dose of gemcitabine plus 2.5 mg intramuscularly weekly of elenagen. The primary end point of the trial was OS.

Comparison with Current Standards

Elenagen’s 12-month increase in median OS compares favorably with other recent advancements. For example, the selective glucocorticoid receptor antagonist relacorilant increased OS from 11.5 to 15.97 months when added to nab-paclitaxel. Elenagen’s results represent a more substantial absolute gain in this specific trial population.

If validated in larger trials, elenagen could shift research toward immunomodulatory, biomarker-independent approaches in gynecologic oncology.

Study Limitations

The trial was limited to 30 evaluable patients, making the findings exploratory, and the study was conducted at only 2 centers in Belarus. Additionally, the study did not incorporate molecular stratification (eg, BRCA status), which might further refine the patient subgroups most likely to benefit.

“We do acknowledge that after progression patients in both arms subsequently received multiple other chemotherapy agents,” noted Krasny et al, authors of the study, in the published research in the International Journal of Gynecological Cancer.¹ “Importantly, the patterns and number of post progression treatments were comparable between the groups and progression-free survival after subsequent therapies did not differ, suggesting that differential post progression management is unlikely to explain the observed overall survival benefit. Importantly, there was no crossover after progression. However, only 30 patients were evaluable for [OS]; this analysis is exploratory and underpowered for definitive survival comparisons.”

REFERENCES

1.Krasny S, Baranau Y, Bakin E, et al. Elenagen, a p62/SQSTM1-encoding plasmid, improves overall survival in patients with platinum-resistant ovarian cancer: a phase II trial. Int JGynecol Cancer. Published January 7, 2026. Accessed February 18, 2026. doi: 10.1016/j.ijgc.2025.104456

2.Efficacy of plasmid elenagen in combination with gemcitabine in patients with platinum-resistant ovarian cancer. ClinicalTrials.gov. Updated August 7, 2023. Accessed February 18, 2026. https://clinicaltrials.gov/study/NCT05979298