Acclaim-1 Trial Evaluating Ozeplasmid and Osimertinib in NSCLC Advances to Final Cohort

Continuation to the final cohort in the dose-escalation portion of the phase 1/2 Acclaim-1 trial (NCT04486833) of ozeplasmid (Reqorsa) in combination with osimertinib (Tagrisso) in patients with late-stage non–small cell lung cancer (NSCLC) has been approved by a safety review committee (SRC), according to Genprex, Inc.¹

The open-label, multicenter, phase 1/2 Acclaim-1 trial is investigating the combination of ozeplasmid and osimertinib in patients with late-stage NSCLC whose disease progressed after receiving osimertinib.

Previously in 2020, the FDA granted fast track designation to the combination in this population.

“The SRC’s recommendation to increase the dosing of [ozeplasmid] 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 Mark Berger, MD, chief medical officer of Genprex, Inc, in the press release. “We look forward to completing enrollment of this final cohort in the first quarter of 2023.”

Within Acclaim-1, patients aged 18 years and older with histologically or cytologically late-stage NSCLC who have activating epidermal growth factor receptor (EGFR) mutations and whose disease progressed after treatment with osimertinib will be enrolled. Patients must have stage III or IV NSCLC or recurrent NSCLC which is deemed not potentially curable by radiotherapy or surgery, have achieved clinical response to osimertinib for 4 months or more, which can be a response of stable disease, and have an ECOG performance status of 0 or 1.2

The phase 1, dose-escalation portion of the trial is expected to enroll up to 18 patients. Here, investigators will determine the maximum tolerated dose and recommended phase 2 dose of the combination.

Then, the dose-expansion of the phase 1 part of the study plans to enroll 66 patients. Among the 66, half must have received prior treatment with only osimertinib and the other half will include patients who had received prior treatment with osimertinib and chemotherapy. This portion of the trial will look at various efficacy end points, including determining the toxicity profiles of patients with different eligibility criteria.

After 19 patients in each cohort are treated, an interim analysis will occur. In the phase 2 portion of the study, approximately 74 patients will be randomized in a 1:1 ratio and receive either ozeplasmid plus osimertinib or osimertinib alone.

In this phase 2 portion of the trial, the primary end points are progression-free survival defined as time from randomization to progression or death and overall response rate. An interim analysis will be performed at 25 events.

“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 these data in the 2 distinct patient populations represented by the 2 expansion cohorts, which we believe will further increase the likelihood of a successful phase 2 trial,” added Berger.

REFERENCE:

1. Genprex receives safety review committee approval to proceed to the final cohort in Acclaim-1 phase 1 dose escalation trial of REQORSA® in combination with Tagrisso® in advanced non-small cell lung cancer. News release. December 14, 2022. Accessed December 15, 2022. https://prn.to/3iY9z4B

2. Quaratusugene ozeplasmid (Reqorsa) and osimertinib in patients with advanced lung cancer who progressed on osimertinib (Acclaim-1). ClinicalTrials.gov. Updated December 1, 2022. Accessed December 14, 2022. https://clinicaltrials.gov/ct2/show/NCT04486833