Non-Viral Gene Therapy Displays Feasibility in EGFR-Mutated NSCLC

Quaratusugene ozeplasmid (Reqorsa), a TUSC2-containing non-viral gene therapy, demonstrated safety and feasibility among a small cohort of patients with EGFR-mutatedadvanced non–small cell lung cancer (NSCLC) when given with osimertinib (Tagrisso), according to findings from the phase 1/2 Acclaim-1 trial (NCT04486833) published in Clinical Lung Cancer.¹

Among 12 patients treated with 0.06 mg/kg (n = 3), 0.09 mg/kg (n = 4), or 0.12 mg/kg (n = 5) of the investigational agent, no dose-limiting toxicities (DLTs) were observed in the study. Three grade 3/4 adverse effects (AEs) deemed related to treatment were observed; 1 patient experienced neutropenia at the lowest dose, and 2 patients experienced lymphopenia, including 1 at the 0.09 mg/kg dose level and 1 at the 0.12 mg/kg dose level.

Additionally, as of the data cutoff date, 1 patient was receiving ongoing therapy, with 8 discontinuations due to disease progression, 1 due to patient withdrawal, 1 lost to follow up, and 1 who died. Moreover, 1 patient experienced a partial response (PR), and an additional 8 experienced stable disease as the best overall response. Three patients had prolonged progression-free survival (PFS), including 1 patient who experienced a PR and was progression free after 32 months, and 2 who experienced stable disease and were free from progression until 9 and 22 months, respectively.

“We believe [quaratusugene ozeplasmid] is an innovative gene therapy that may benefit many [patients with] lung cancer, and we are pleased to see these data for [quaratusugene ozeplasmid] published and shared with the scientific community,” Ryan Confer, president and chief executive officer at Genprex, the agent’s developer, said in a news release on the phase 1/2 trial results.² “Genprex is thankful to the patients who participated in this study, along with the investigators who made the completion of the study possible. We believe this new mechanism and novel approach targeting lung cancer, which comes with a strong safety profile and early signs of efficacy, is paving new ground in the fight against lung cancer.”

According to the developers, the dose-escalation portion of the open-label phase 1/2 trial established a recommended phase 2 dose (RP2D) of 0.12 mg/kg.

Those enrolled on the open-label phase 1/2 trial had stage III/IV NSCLC and experienced disease progression following the most recent treatment regimen. Additionally, patients must have been 18 years and older, had EGFR-mutated disease, and had a clinical response of stable disease or better with osimertinib alone or with pemetrexed and a platin for a minimum of 4 months.

Patients received quaratusugene ozeplasmid intravenously every 21 days across 3 dose levels—0.06, 0.09, or 0.12 mg/kg—over 30 minutes plus 80 mg of daily oral osimertinib. The study followed a standard dose-escalation schema, and doses were not increased for individual patients. Additionally, acetaminophen (Tylenol) and diphenhydramine (Benadryl) were given before treatment to mitigate infusion-related reactions.

The primary end point of the phase 1 portion of the study was the maximum tolerated dose or RP2D.³ For the phase 2 portion of the study, the primary end points were objective response rate and PFS. Duration of response, pharmacokinetics, time to progression, overall survival, and safety were among the secondary end points assessed on the trial. Safety was assessed using the CTCAE v5.0 scale.

The most common treatment-emergent AEs included delayed infusion-related reactions (50.0%), diarrhea (41.7%), myalgia (41.7%), headaches (33.3%), influenza-like illness (33.3%), and nausea (33.3%). Delayed infusion-related reactions were managed with prophylactic steroids, acetaminophen, and diphenhydramine; symptoms declined with repeat cycles. Cytokine release syndrome occurred in 25.0% of patients; all were treated at the 0.12 mg/kg dose level.

References

1. Spira AI, Berz D, Jotte RM, Pachipala KK, Berger MS. Dose escalation trial of the combination of osimertinib and quaratusugene ozeplasmid gene therapy in patients with advanced NSCLC. Clin Lung Cancer. Published November 17, 2025. doi:10.1016/j.cllc.2025.11.009
2. Data from Genprex's Acclaim-1 phase 1 gene therapy clinical trial published in Clinical Lung Cancer. News release. Genprex, Inc. November 24, 2025. Accessed November 24, 2025. https://tinyurl.com/mr227bre
3. Quaratusugene ozeplasmid (Reqorsa) and osimertinib in patients with advanced lung cancer who progressed on osimertinib (Acclaim-1). ClinicalTrials.gov. Updated November 5, 2025. Accessed November 24, 2025. https://tinyurl.com/2pan84mc