The safety review committee for the phase 1/2 Acclaim-1 trial has ruled that the study evaluating quaratusugene ozeplasmid in combination with osimertinib in patients with advanced non–small cell lung cancer can proceed to the phase 2 expansion portion.
The safety review committee for the phase 1/2 Acclaim-1 trial (NCT04486833) has ruled that the study evaluating quaratusugene ozeplasmid (Reqorsa) in combination with osimertinib (Tagrisso) in patients with advanced non–small cell lung cancer can proceed to the phase 2 expansion portion.1
Full safety data from the phase 1 portion of the trial did not reveal any dose-limiting toxicities. The recommended phase 2 dose (RP2D) of quaratusugene ozeplasmid was established as 0.12 mg/kg. Additionally, quaratusugene ozeplasmid was reported to be generally well tolerated, with evidence of early efficacy observed. Full data from this part of the trial will be presented at the 2023 ASCO Annual Meeting.
“We are proud of the notable progress we made during the phase 1 portion of the Acclaim-1 clinical trial, and the safety review committee recommendation to move into the phase 2 expansion portion of the trial is another validation for our [quaratusugene ozeplasmid] development program,” Rodney Varner, chairman, president, and chief executive officer of Genprex, stated in a news release. “As we move into the phase 2 expansion portion of the trial, we remain steadfast in our efforts to bring new therapies to lung cancer patients with unmet medical need.”
Quaratusugene ozeplasmid is comprised of Genprex’s unique, proprietary Oncoprex nanoparticle delivery system and a plasmid that expresses the TUSC2 tumor suppressor gene. Given intravenously, the agent is designed to specifically target cancer cells. Upon uptake into a cancer cell, the TUSC2 gene is expressed, and the TUSC2 protein can restore certain defective functions arising in the cancer cell.
Quaratusugene ozeplasmid possesses a multimodal mechanism of action that allows it to interrupt cell-signaling pathways that cause replication and proliferation of cancer cells, re-establish pathways for apoptosis in these cells, and modulate the immune response against cancer cells.
In January 2020, the FDA granted fast track designation to quaratusugene ozeplasmid in combination with osimertinib for the treatment of patients with NSCLC harboring EGFR mutations that progressed after treatment with osimertinib alone.2
The open-label, multicenter Acclaim-1 trial is evaluating the combination of quaratusugene ozeplasmid and osimertinib in patients who are at least 18 years of age and have histologically or cytologically documented EGFR-mutated stage III/IV NSCLC or recurrent disease that is not potentially curable by radiotherapy or surgery.3 Patients must have experienced radiological progression on osimertinib following a clinical response to the EGFR inhibitor for at least 4 months, which can include stable disease.
Patients with asymptomatic brain metastases are allowed to enroll if they have no history of seizures in the 6 months prior to enrollment, complete definitive treatment at least 21 days before enrollment, are off steroids for their metastases for at least 7 days, and imaging demonstrates stability or regression of the metastases.
Key exclusion criteria include prior gene therapy; standard chemotherapy or monoclonal antibodies for NSCLC within 21 days of study treatment; the presence of other actionable mutations with other approved targeted therapies; or radiotherapy to the skull, spine, thorax, or pelvis within 30 days of enrollment.
In phase 1, patients received quaratusugene ozeplasmid intravenously at doses of 0.06 mg/kg, 0.09 mg/kg, or 0.12 mg/kg once every 21 days plus 80 mg of osimertinib per day. The RP2D of 0.12 mg/kg of quaratusugene ozeplasmid was used in subsequent patients after it was established.
In phase 2, patients will be randomly assigned to receive the RP2D of 0.12 mg/kg of IV quaratusugene ozeplasmid once every 3 weeks plus 80 mg of oral osimertinib per day or osimertinib monotherapy.
Establishing the RP2D and overall response rate (ORR) were the primary end points of the phase 1 portion of the research. Progression-free survival (PFS) is the primary end point for the phase 2 portion. Secondary end points in phase 1 included PFS, pharmacokinetics, time to progression, overall survival (OS), and safety. The phase 2 secondary end points consist of OS, ORR, pharmacokinetics, and safety.