Quaratusugene Ozeplasmid Shows Early Efficacy in 2 Lung Cancer Trials
In the Acclaim-1 and Acclaim-3 trials, prolonged progression-free survival and partial remission were observed with quaratusugene ozeplasmid plus osimertinib and atezolizumab for advanced lung cancer treatment.
illustration of Lungs, medical concept© yodiyim - stock.adobe.com
Prolonged progression-free survival (PFS) rates were observed in the Acclaim-1 trial (NCT04486833) of quaratusugene ozeplasmid (Reqorsa) in combination with the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor osimertinib (Tagrisso) for the treatment of non–small cell lung cancer (NSCLC).1
Additionally, the first patient treated in the Acclaim-3 study (NCT05703971) achieved a partial remission (PR) from the start of maintenance therapy. This study is evaluating quaratusugene ozeplasmid when combined with the checkpoint inhibitor atezolizumab (Tecentriq) for patients with extensive stage (ES)-small cell lung cancer (SCLC) who have not experienced tumor progression following initial standard treatment with atezolizumab and chemotherapy.
"We are excited by these early and promising patient responses to [quaratusugene ozeplasmid] treatment, particularly as these patients represent some of the most difficult to treat lung cancer patient populations. There is significant unmet medical need for patients afflicted with lung cancer, as nearly all patients' disease progresses following treatment, even when treated with today's most advanced targeted therapies and immunotherapies. This leaves patients with limited therapeutic options,” said Ryan Confer, president and chief executive officer of Genprex, in a press release. “We are thrilled our novel gene therapy treatment for lung cancer, [quaratusugene ozeplasmid], is demonstrating early evidence of efficacy with a favorable safety profile. We look forward to continuing to evaluate [quaratusugene ozeplasmid] in our lung cancer clinical trials while we advance our efforts to bring new therapies to those battling cancer."
In addition to these 2 studies, quaratusugene ozeplasmid is also being evaluated in the Acclaim-2 trial (NCT05062980) when given in combination with pembrolizumab (Keytruda) in patients with late-stage NSCLC whose disease has progressed after treatment with pembrolizumab. This trial is now stopping the enrollment of new patients with NSCLC.
About Acclaim-1
Acclaim-1 is an open-label, multicenter, phase 1/2 study evaluating the combination of quaratusugene ozeplasmid and osimertinib in patients with late-stage NSCLC whose disease progressed after receiving osimertinib.2
Those aged 18 years and older with histologically or cytologically late-stage NSCLC who have activating EGFR mutations and whose disease progressed after treatment with osimertinib are eligible for enrollment. Patients must also 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 to be included in the study.
The phase 1, dose-escalation portion of the trial aims to determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of the combination. Two patients from phase have had prolonged PFS. These patients are continuing to receive treatment in the study.1
One of the patients has received the treatment combination for over 2 years. This patient was treated with osimertinib and chemotherapy previously, continues to receive the combination of quaratusugene ozeplasmid and osimertinib, and attained a PR after the second course of the combination. Additionally, this patient has maintained this response for more than 2 years.
The second patient has had stable disease without disease progression for greater than 15 months. They also are continuing to receive quaratusugene ozeplasmid and osimertinib.
The study also includes a phase 2a expansion portion which includes 2 cohorts with a planned 33 patients each. The first cohort included patients who had previously received only treatment with osimertinib. Here, patients who are progressing on prior osimertinib will be randomly assigned 1:1 to receive ozeplasmid and osimertinib or platinum-based chemotherapy.
The other cohort was for patients who had previously received both treatment with osimertinib and chemotherapy. Now, the company plans to limit its enrollment efforts for the phase 2a expansion portion of the Acclaim-1 study to patients who received only prior osimertinib. No more patients will be enrolled in the second cohort. Further, an interim analysis is planned and the enrollment of the first 19 patients in the phase 2a expansion portion of the study is expected to be completed in the first half of 2025.
About Acclaim-3
The open-label, dose-escalation, clinical response, phase 1/2 Acclaim-3 study is assessing maintenance therapy of quaratusugene ozeplasmid plus atezolizumab in patients with ES-SCLC.3 Patients are being enrolled once they receive initial treatment with 3 to 4 cycles of carboplatin, etoposide, and atezolizumab and achieve complete response, partial response, or stable disease. Then, patients will be given quaratusugene ozeplasmid and atezolizumab as maintenance therapy every 21 days until disease progression.
The company anticipates the phase 1 dose-escalation portion of the study to be completed during the second half of 2024. Once it is finished, the phase 2 expansion portion of the study will begin.
The dose-escalation portion of phase 1 includes up to 12 patients. Experts aim to determine the MTD of the combination. If there are no dose-limiting toxicities observed during phase 1, the highest dose to be evaluated will serve as the RP2D.
Phase 2 will then include approximately 50 patients who will be given the combination until disease progression or unacceptable toxicity. The primary end point for phase 2 is to determine the 18-week PFS rate from the time of the start of maintenance therapy with the combination in patients with ES-SCLC. Patients will also be followed for survival. Once the 25th patient enrolled and treated with the combination reaches 18 weeks of follow-up, a phase 2 futility analysis will be performed. This portion of the study is expected to begin in the second half of 2024.
Notably, the first patient treated in the phase 1 dose-escalation portion of the study experienced a PR, which is defined as at least a 30% decrease in tumor size, from the time the patient had a baseline CT scan after induction therapy and prior to the start of maintenance therapy to the time of the CT scan performed after 2 cycles of maintenance therapy.
"This patient's response was not expected during maintenance therapy with [atezolizumab] alone, and we believe these results are promising and a positive early indication for the study. Once ES-SCLC patients begin maintenance therapy with [atezolizumab], median PFS is very short; only 2.6 months, and further tumor regression rarely occurs. The ES-SCLC patient in the Acclaim-3 clinical trial treated with our combination therapy experienced PR, but asymptomatic disease progression was diagnosed by CT scan 3 months after the start of maintenance therapy. We find this positive result to be promising, particularly because this patient was treated with the lower of 2 doses planned for the phase 1 portion of this clinical trial, and we are hopeful that the combination of [quaratusugene ozeplasmid] and [atezolizumab] will improve outcomes and help extend the lives of these very difficult to treat lung cancer patients," added Mark Berger, MD, chief medical officer of Genprex, in a press release.1
