Acclaim-2 Begins Enrollment to Asses Ozeplasmid Plus Pembrolizumab in Late-Stage NSC Lung Cancer
The phase 1/2 study (NCT05062980) has officially opened enrollment for patients with late-stage non-small cell lung cancer, with plans to initiate patient screening.
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Genprex, Inc, has announced that it has begun the enrollment process for the phase 1/2 Acclaim-2 trial (NCT05062980) of quaratusugene ozeplasmid (Reqorsa) in combination with pembrolizumab (Keytruda) in the treatment of patients with late-stage non-small cell lung cancer (NSCLC) whose experienced disease progression post pembrolizumab treatment.1
The combination of quaratusugene, ozeplasmid, and osimertinib was fast tracked by the FDA in 2020 for the treatment of patients with advanced NSCLC who progressed on osimertinib as part of the Acclaim-1 study (NCT04486833). This year, the treatment was granted fast track designation for the treatment of the Acclaim-2 patient population.2 The first patient with advanced NSCLC in the phase 1/2 Acclaim-1 trial was dosed with ozeplasmid in combination with osimertinib after disease progression on osimertinib alone in March 2022.
Mark S. Berger, MD, chief medical officer of Genprex, Inc., said in a press release that the company was "pleased" to have initiated enrollment, and "expect[s] to promptly begin screening patients for their eligibility to participate in the trial."
"This marks an important milestone in our clinical development program for Reqorsa as we continue to engage with prestigious clinical trial sites to build patient enrollment and provide hope to lung cancer patients who suffer from this devastating disease and who are in desperate need of new treatment options," Berger said. "We look forward to completing the phase 1 portion of Acclaim-2 by the end of the first quarter of 2023 and to generating data to show the synergistic effects Reqorsa combined with immunotherapies can have in patients."
Preclinical data has previously shown synergy between quaratusugene ozeplasmid and pembrolizumab, with the combination proving better efficacy than pembrolizumab alone in increasing the survival of mice with a humanized immune system that had metastatic lung cancer. Prior studies have also recorded multiple immune system effects from ozeplasmid treatment, including an increase in natural killer cells and a decrease in myeloid-derived suppressor cells, which were deemed likely to contribute to the results observed with the use of pembrolizumab.
Phase 1 of the open-label, multicenter Acclaim-2 trial will enroll up to 30 patients in a dose-escalation study and will determine the maximum tolerated dose of the combination of quaratusugene ozeplasmid and pembrolizumab.3 The phase 1 portion of the study will involve up to 3 dose-escalation cohorts who will be treated with quaratusugene ozeplasmid of up to 0.12 mg/kg in combination with a 200-mg fixed dose of pembrolizumab administered once via intravenous (IV) infusion during each 21-day treatment cycle. A total of 3 doses of quaratusugene ozeplasmid will be tested (0.06, 0.09, and 0.12 mg/kg) administered on day 1 of a 21-day treatment cycle. The primary end point in phase 1 of the trial is the maximum tolerated dose.
Phase 2 of the study will enroll approximately 126 patients who will be randomly assigned in 2:1 fashion to either quaratusugene ozeplasmid and pembrolizumab combination therapy or docetaxel and/or ramucirumab (Cyramza). In phase 2 of the study, patients will receive the recommended phase 2 dose of quaratusugene ozeplasmid intravenously on day 1 in addition to a fixed dose of pembrolizumab at 200 mg every 21 days until progression or unacceptable toxicity. The primary end point of phase 2 is progression-free survival defined as time from randomization to progression or death.
Enrollment in Acclaim-2 is open to patients aged 18 years and older with histologically or cytologically documented NSCLC with locally advanced or metastatic stage IV disease. Requirements also include achieved clinical benefit to prior pembrolizumab/platinum-based chemotherapy for at least 3 months and subsequently progression with radiological tumor assessment performed within 28 days of enrollment, an ECOG performance score from 0 to 1, and adequate organ function.
