Genprex, Inc. (NASDAQ:GNPX) has announced that the Safety Review Committee (SRC) has approved continuation to the third and final cohort in the dose escalation Phase 1 portion of the Acclaim-1 Phase 1/2 clinical trial of REQORSA in combination with Tagrisso (osimertinib) to treat late-stage non-small cell lung cancer (NSCLC).
The SRC is comprised of three physicians who are principal investigators in the trial. The SRC may recommend that the trial continues at the same dose or at a lower dose, that it escalates to a higher dose, or that the study be terminated altogether due to safety concerns.
"The SRC's recommendation to increase the dosing of REQORSA is further confirmation of its favorable safety profile and it enables us to advance Acclaim-1 into the final cohort of the Phase 1 dose escalation portion of the study," said Dr Mark Berger, chief medical officer of Genprex. "We look forward to completing enrollment of this final cohort in the first quarter of 2023."
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Acclaim-1 is an open-label, multi-center Phase 1/2 clinical trial evaluating the company's lead drug candidate, REQORSA Immunogene Therapy, in combination with Tagrisso in patients with late-stage NSCLC, whose disease progressed after treatment with Tagrisso.
In 2020, the combination of REQORSA and osimertinib received US Food and Drug Administration's (FDA) Fast Track Designation for the treatment of the Acclaim-1 patient population.
Dose expansion portion of the study
The Accaim-1 trial includes up to three sequential dose escalation cohorts that will treat study participants with REQORSA intravenously on Day 1 in addition to osimertinib 80 mg fixed dose oral daily tablet during 21-day treatment cycles until disease progression or unacceptable toxicity.
The first group received REQORSA IV infusion at 0.06 mg/kg, the second group received 0.09 mg/kg, and the third group will receive 0.12 mg/kg.
Following the successful completion of the Phase 1 dose escalation portion of the Acclaim-1 study, the company will advance into the dose expansion portion of the study, which will evaluate the toxicity profile of REQORSA in combination with Tagrisso in patients with different eligibility criteria, and will also evaluate efficacy and other endpoints.
"The principal advantage of adding the dose expansion portion to Acclaim-1 is to gain efficacy data earlier than we would otherwise have received it from the Phase 2 portion of the study. We also will receive this data in the two distinct patient populations represented by the two expansion cohorts, which we believe will further increase the likelihood of a successful Phase 2 trial," noted Dr Berger.
Acclaim-1
Genprex said it expects the dose escalation Phase 1 portion of the Acclaim-1 trial to enroll up to 18 patients to determine the maximum tolerated dose of the combination.
The dose expansion Phase 1 portion of the study will then enroll 66 patients, half of whom will be patients who had received only prior Tagrisso treatment and the other half patients who had received prior Tagrisso treatment and chemotherapy, to determine toxicity profiles of patients with different eligibility criteria, as well as efficacy and other endpoints.
There will be an interim analysis following the treatment of 19 patients in each cohort. The Phase 2 portion of the study is expected to enroll around 74 patients to be randomized 1:1 to receive either REQORSA and Tagrisso combination therapy or Tagrisso monotherapy.
The primary endpoint of the Phase 2 portion of the trial is progression-free survival, which is defined as time from randomization to progression or death. An interim analysis will be performed at 25 events.
REQORSA Immunogene therapy (quaratusugene ozeplasmid) for NSCLC uses Genprex's unique, proprietary ONCOPREX Nanoparticle Delivery System, which is the first systemic gene therapy delivery platform used for cancer in human clinical trials. The plasmid portion of REQORSA contains the TUSC2 gene, a tumor suppressor gene
Tagrisso is AstraZeneca's largest-selling drug with 2021 sales of over $5 billion.
Genprex is a clinical-stage gene therapy company focused on developing life-changing therapies for patients with cancer and diabetes. The company's technologies are designed to administer disease-fighting genes to provide new therapies for large patient populations with cancer and diabetes who currently have limited treatment options.
Contact the author at jon.hopkins@proactiveinvestors.com