Dosing Begins in Phase 1/2 Study of Reqorsa Plus Osimertinib in Advanced NSCLC

The first patient with advanced non–small cell lung (NSCLC) in the phase 1/2 Acclaim-1 clinical trial had been dosed with quaratusugene ozeplasmid (Reqorsa) in combination with osimertinib (Tagrisso) after disease progression on osimertinib alone, according to a press release issued by Genprex, Inc.¹

Quaratusugene ozeplasmid is an immunogene therapy, designed to be injected directly into tumor cells to interrupt cell signaling pathways and recreate pathways for apoptosis in cancer cells. Quaratusugene ozeplasmid also modulates the immune response against cancer cells and blocks the development of drug resistance.

“This is an exciting milestone for Genprex that we believe brings us one step closer to achieving our goal to validate the potential benefits of Reqorsa in NSCLC patients who have life-limiting disease and few treatment options,” stated Mark S. Berger, MD, chief medical officer of Genprex, in a press release. “Based on both the preclinical data and previous clinical data, Reqorsa has the potential to improve the response to current targeted therapies, such as Tagrisso, for this study patient population. We look forward to continuing to advance this important trial.”

In 2020, the combination of quaratusugene ozeplasmid and osimertinib was granted fast track designation by the FDA for the treatment of patients with advanced NSCLC who progressed on osimertinib as studied in Acclaim-1 (NCT04486833).

Acclaim-1 is an open-label, multi-center, phase 1/2 study. Following a 3 + 3 dose-escalation design, the study will find the recommended phase 2 dose (RP2D) of quaratusugene ozeplasmid with osimertinib in 92 patients with advanced NSCLC. The primary outcomes are determining the maximum-tolerated dose based on the number of patients with dose-limiting toxicities, and progression-free survival. The secondary end points include overall response rate, overall survival, duration of treatment, and the incidence of adverse events (AEs).²

In phase 1, the study will include up to 3 sequential dose escalation cohorts of patients who will received osimertinib 80 mg fixed dose orally daily on day 1 of 21-day cycles. Treatment with osimertinib will be continued until disease progression or unacceptable toxicity. In terms of the experimental agents, patients in the phase 1 group will receive quaratusugene ozeplasmid 0.06 mg/kg given by intravenous (IV), whereas those in group 2 will receive 0.09 mg/kg infusions, and those in group 3 will received 0.12 mg/kg infusions.

In the phase 2 portion of the study, patients will receive the combination of IV quaratusugene ozeplasmid at the RP2D and osimertinib 80 mg fixed dose orally daily on day 1 of 21-day treatment cycles. Treatment with the combination will continue until disease progression or unacceptable toxicity.

Those included in the study are patients with histologically or cytologically documented NSCLC that is stage III or IV, or recurrent and positive for EGFR mutation. All patients must have achieved a response to osimertinib for more than 4 months, have radiographical progression on or after osimertinib, have an ECOG performance status of 0 to 1, and have adequate renal, hepatic, and cardiac function as well as satisfactory lab values at screening.

Patients with brain metastases are permitted to enroll given they have no history of seizure is the past 6 months, completed treatment more than 21 days prior, are no longer taking steroids by 7 days before the start of the study, and their post-treatment imaging demonstrated stability or regression of brain metastases. Those who have undergone major surgery must be at least 28 days post-surgery before enrolling in Acclaim-1.

The study is actively recruiting patients who meet the inclusion criteria at centers located in Colorado, Maryland, New York, Texas, and Virginia.

“Despite recent advances in immuno-oncology and other targeted treatments, NSCLC remains a significant unmet medical need as resistance to Tagrisso and other targeted therapies is a common clinical problem,” Berger added, in the press release.¹ “Reqorsa is a pan-kinase inhibitor shown to inhibit both the EGFR and AKT oncogenic kinase pathways. We believe that Reqorsa’s multimodal activity will block emerging bypass pathways, reducing the probability that drug resistance develops.”

_References:

_{1. Genprex announces first patient dosed in phase 1/2 Acclaim-1 clinical trial of Reqorsa™ immunogene therapy in combination with Tagrisso® to treat non-small cell lung cancer. News release. March 2, 2022. Accessed March 4, 2022. https://bit.ly/35MdYkD}

_{2. Reqorsa (quaratusugene ozeplasmid) and osimertinib in patients with advanced lung cancer who progressed on osimertinib (Acclaim-1). Cliinicaltrials.gov. Accessed March 4, 2022. https://bit.ly/3IIdqLm}