Genprex, Inc. (NASDAQ: GNPX) has received the green light from its Safety Review Committee (SRC) to escalate to the highest planned dose group of 0.12 mg/kg in the Phase 1 dose-escalation portion of the Acclaim-3 clinical trial. This trial is evaluating Reqorsa Gene Therapy (quaratusugene ozeplasmid) in combination with Tecentriq (atezolizumab) as a maintenance therapy for patients with extensive stage small cell lung cancer (ES-SCLC).
The SRC's decision follows the completion of the 0.09 mg/kg dose group, during which no dose-limiting toxicities (DLTs) were observed. The Acclaim-3 trial previously received Fast Track Designation from the U.S. Food and Drug Administration (FDA) for this patient population, and Reqorsa has also been granted Orphan Drug Designation for the treatment of SCLC.
Favorable Safety Profile and Early Efficacy Signals
Ryan Confer, President and CEO of Genprex, stated that the SRC's recommendation validates the Reqorsa development program. He highlighted the favorable safety profile demonstrated in the Phase 1 portion of the trial, which marks the first study of Reqorsa in SCLC patients. Notably, the first patient treated in the Phase 1 dose escalation experienced a partial remission, defined as a 30% decrease in tumor size after two cycles of maintenance therapy.
While a subsequent CT scan after four cycles showed disease progression due to the growth of a previously unmeasurable lesion, the company believes that Reqorsa may be providing clinical benefit. This is based on the fact that the patient had already received four cycles of Tecentriq during induction therapy, suggesting that responses to Tecentriq would likely have occurred earlier.
Acclaim-3 Trial Design and Endpoints
The Acclaim-3 trial is an open-label, multi-center Phase 1/2 clinical trial. In the Phase 1 dose escalation, patients receive Reqorsa and Tecentriq until disease progression or unacceptable toxicity. The primary endpoint of Phase 1 is to determine the maximum tolerated dose (MTD) or recommended Phase 2 dose (RP2D).
Following Phase 1, the trial will proceed to a Phase 2 expansion, enrolling 50 patients at 10 to 15 U.S. sites. The primary endpoint of Phase 2 is the 18-week progression-free survival rate from the start of maintenance therapy. Patients will also be followed for overall survival. A Phase 2 futility analysis is planned after the 25th patient reaches 18 weeks of follow-up. Genprex anticipates starting the Phase 2 expansion in the second half of 2024, contingent on enrollment in the 0.12 mg/kg dose group.
Preclinical Data Supports Combination Therapy
Data presented at the October 2023 AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics from studies in humanized mouse models of SCLC demonstrated that the combination of REQORSA and atezolizumab provided significantly better control of xenograft tumor growth compared to either agent alone. These studies also showed increased immune cell infiltration in tumors treated with the combination, suggesting a synergistic effect.
