On October 15, 2024 Genprex, Inc. ("Genprex" or the "Company") (NASDAQ: GNPX), a clinical-stage gene therapy company focused on developing life-changing therapies for patients with cancer and diabetes, reported that it has completed the 0.09 mg/kg dose group of the Phase 1 dose escalation portion of the Acclaim-3 clinical trial of Reqorsa Gene Therapy (quaratusugene ozeplasmid) in combination with Tecentriq (atezolizumab) as maintenance therapy for patients with extensive stage small cell lung cancer (ES-SCLC) (Press release, Genprex, OCT 15, 2024, View Source [SID1234647201]). In addition, the Safety Review Committee (SRC) has approved escalation to the highest dose group of 0.12 mg/kg. The combination of REQORSA and atezolizumab previously received U.S. Food and Drug Administration’s (FDA) Fast Track Designation 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.
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"We believe the SRC’s recommendation to advance to the highest dose group of the Phase 1 portion of the trial is another clinical validation for our REQORSA development program," said Ryan Confer, President and Chief Executive Officer. "We are proud of the achievements so far in the Phase 1 portion of the trial, which has demonstrated a favorable safety profile for REQORSA in the first trial to use REQORSA for SCLC patients. We look forward to continuing to treat these patients while we work toward bringing new therapies to lung cancer patients with unmet medical need."
There were no dose limiting toxicities (DLTs) in this dose group and the SRC recommended moving up to the highest dose group planned in the trial. As previously announced, the first patient treated in the Phase 1 dose escalation portion of the Acclaim-3 trial had a partial remission, which is defined as at least a thirty percent (30%) decrease in tumor size, from prior to the start of maintenance therapy to the time of the CT scan performed after two cycles of maintenance therapy. A CT scan performed after four cycles of maintenance therapy (three months), confirmed that the patient had a 30% decrease in tumor size in measurable lesions; however, one lesion not previously measurable had grown in size, thus leading to a conclusion of disease progression at that time. As the maintenance therapy consists of REQORSA and Tecentriq, and the patient had already received four cycles of Tecentriq during induction therapy and thus responses to Tecentriq would likely have occurred earlier, the Company believes this suggests that REQORSA may be providing clinical benefit.
The SRC is comprised of three physicians who are principal investigators in the trial. The SRC may recommend that the trial continue at the same dose or at a lower dose, that it escalate to a higher dose, or that the study be terminated altogether due to safety concerns.
In the Phase 1 dose escalation portion of the Acclaim-3 clinical trial, patients are treated with REQORSA and Tecentriq until disease progression or unacceptable toxicity is experienced. The primary endpoint of the Phase 1 escalation portion is to determine the maximum tolerated dose (MTD) or recommended Phase 2 dose (RP2D).
The Phase 1 portion of the trial has two dose groups: 0.09 mg/kg, which has been completed, and 0.12 mg/kg which will now be enrolled. After the Phase 1 portion is complete, the Phase 2 expansion portion will enroll 50 patients at 10 to 15 U.S sites. Patients will be treated with REQORSA and Tecentriq until disease progression or unacceptable toxicity is experienced. The primary endpoint of the Phase 2 portion is to determine the 18-week progression-free survival rate from the time of the start of maintenance therapy with REQORSA and Tecentriq in patients with ES-SCLC. Patients will also be followed for survival. A Phase 2 futility analysis will be performed after the 25th patient enrolled and treated reaches 18 weeks of follow up. The Company continues to anticipate completion of enrollment in the Phase 1 dose escalation portion of the trial and to start the Phase 2 expansion portion in the second half of 2024, dependent on the number of patients needed to be enrolled in the 0.12 mg/kg dose group.
Data presented at the October 2023 AACR (Free AACR Whitepaper)-NCI-EORTC AACR-NCI-EORTC (Free AACR-NCI-EORTC Whitepaper) International Conference on Molecular Targets and Cancer Therapeutics (EORTC-NCI-AACR) (Free ASGCT Whitepaper) (Free EORTC-NCI-AACR Whitepaper) from studies in humanized mouse models of SCLC show that the combination of REQORSA and atezolizumab provides significantly better control of xenograft tumor growth than either agent alone. The data from these studies also demonstrated increased immune cell infiltration in the tumors with the combination of REQORSA and Tecentriq compared to Tecentriq alone.
About Acclaim-3
The Acclaim-3 clinical trial is an open-label, multi-center Phase 1/2 clinical trial evaluating the Company’s lead drug candidate, Reqorsa Gene Therapy, in combination with Genentech, Inc.’s Tecentriq (atezolizumab) as maintenance therapy in patients with extensive stage small cell lung cancer (ES-SCLC) who did not develop tumor progression after receiving Tecentriq and chemotherapy as initial standard treatment.