Genprex, Inc. (NASDAQ: GNPX) has announced the advancement of its Acclaim-3 clinical trial to Phase 2, evaluating Reqorsa® Gene Therapy (quaratusugene ozeplasmid) in combination with Tecentriq® (atezolizumab) as maintenance therapy for patients with extensive stage small cell lung cancer (ES-SCLC). This follows the completion of the Phase 1 dose escalation portion of the trial, which demonstrated a favorable safety profile.
The Safety Review Committee (SRC) has determined the Recommended Phase 2 Dose (RP2D) of REQORSA to be 0.12 mg/kg, the highest dose level tested in Phase 1. The Phase 2 expansion will evaluate the 18-week progression-free survival rate among approximately 50 patients at 10 to 15 U.S sites.
Acclaim-3 Trial Design and Endpoints
The Acclaim-3 trial is an open-label, multi-center Phase 1/2 clinical trial. The primary endpoint of the Phase 2 portion is to determine the 18-week progression-free survival rate from the start of maintenance therapy with REQORSA and Tecentriq in patients with ES-SCLC. Patients will also be followed for survival. An interim analysis will be performed after the 25th patient enrolled and treated reaches 18 weeks of follow up.
Reqorsa Mechanism and Rationale
REQORSA contains a plasmid that expresses TUSC2, a tumor suppressor gene protein. Nearly 100% of SCLCs have reduced or no TUSC2 protein expression, and 41% completely lack TUSC2 protein expression. Preclinical data presented at the October 2023 AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics, using humanized mouse models of SCLC, showed that the combination of REQORSA and Tecentriq provides significantly better control of tumor burden than either agent alone. The data from these studies also suggest that a combination treatment of REQORSA and Tecentriq can promote a significantly increased tumor cell killing effect in SCLC xenografts compared to that of Tecentriq alone.
The combination of REQORSA and atezolizumab has received Fast Track Designation from the FDA for the treatment of the Acclaim-3 patient population, and the FDA has also granted Orphan Drug Designation to REQORSA for the treatment of SCLC.
Leadership Commentary
"We are excited to begin the Phase 2 expansion portion of Acclaim-3, which will determine the 18-week Progression Free Survival (PFS) rate of REQORSA and Tecentriq combination maintenance therapy," said Mark Berger, MD, Chief Medical Officer at Genprex. "ES-SCLC has a poor prognosis with a median PFS of 5.2 months. Those patients receiving Tecentriq as maintenance therapy have a median PFS of 2.6 months after the start of maintenance therapy. We look forward to studying the combination of REQORSA and Tecentriq as we work to advance our innovative gene therapy."
