Acclaim-2 Explores Ozeplasmid Plus Pembrolizumab in Late-Stage NSCLC

Acclaim-2 has opened enrollment for patients with late-stage non-small cell lung cancer and will begin screening patients for their eligibility to participate in the trial.

The phase 1/2 Acclaim-2 trial (NCT05062980) evaluating ozeplasmid (Reqorsa) in combination with pembrolizumab (Keytruda) in patients with late-stage non-small cell lung cancer (NSCLC) whose disease progressed after treatment with pembrolizumab has announced the opening of enrollment, according to a press release by Genprex, Inc.1

"We are pleased to have opened Acclaim-2 for patient enrollment and expect to promptly begin screening patients for their eligibility to participate in the trial," stated Mark S. Berger, MD, chief medical officer of Genprex, Inc., in a press release. "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. 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."

In 2020, the combination of quaratusugene ozeplasmid and osimertinib was granted fast track designation by the FDA for the treatment of patients with advanced NSCLC who progressed on osimertinib as studied in Acclaim-1 (NCT04486833), and in 2022, the FDA granted it fast track designation for treatment of the Acclaim-2 patient population.2

Preclinical data has also previously shown synergy between ozeplasmid and pembrolizumab, demonstrating the combination to be more effective than pembrolizumab alone in increasing the survival of mice with a humanized immune system that had metastatic lung cancer.

The studies also recorded multiple effects of ozeplasmid on the immune system, such as an increase in natural killer cells and a decrease in myeloid derived suppressor cells in the tumor, which are likely to contribute to what was examined with the use of pembrolizumab.

Additionally, the first patient with advanced NSCLC in the phase 1/2 Acclaim-1 trial had been dosed with ozeplasmid in combination with osimertinib after disease progression on osimertinib alone in March 2022.

Phase 1 of the open-label, multi-center Acclaim-2 trial will enroll up to 30 patients in a dose escalation study and looks to determine the maximum tolerated dose of the combination made up to ozeplasmid and pembrolizumab.3The phase 2 portion of the study aims to enroll approximately 126 patients who will be randomized 2:1 to receive either ozeplasmid and pembrolizumab combination therapy or docetaxel and/or ramucirumab (Cyramza).

Enrollment in Acclaim-2 is open to patients aged 18 and older with histologically or cytologically documented NSCLC with locally advanced or metastatic stage IV disease. Additional requirements include an achieved clinical benefit to prior pembrolizumab/platinum-based chemotherapy for at least 3 months and subsequently progressed with radiological tumor assessment performed within 28 days of enrollment, an ECOG performance score from 0 to 1, and adequate organ function.

The phase 1 portion of the study will involve up to 3 dose escalation cohorts who will be treated with ozeplasmid of up to 0.12 mg/kg in combination with a 200mg, fixed dose of pembrolizumab administered once via intravenous (IV) infusion during each 21-day treatment cycle. A total of 3 doses of ozeplasmid will be tested (0.06, 0.09 and 0.12 mg/kg administered on Day 1 of a 21-day treatment cycle).

In phase 2 of the study, patients will receive the recommended phase 2 dose of 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 in phase 1 of the trial is maximum tolerated dose while the end point of phase 2 is progression-free survival defined as time from randomization to progression or death.

References:
  1. Genprex announces the opening for enrollment of its phase 1/2 Acclaim-2 clinical trial of REQORSA immunogene therapy in combination with keytruda® to treat non-small cell lung cancer. News Release. Genprex Inc. March 31, 2022. Accessed April 5, 2022. https://bit.ly/3DFDQeR
  2. Genprex receives FDA fast track designation for REQORSA - Keytruda for NSCLC treatment. News Release. Genprex Inc. January 3, 2022. Accessed April 5, 2022. https://bit.ly/3u9bLcY
  3. Reqorsa (cuaratusugene czeplasmid) in combination With pembrolizumab in previously treated non-small lung cancer (Acclaim-2). Clinicaltrials.gov. Accessed April 5, 2022. https://bit.ly/3j1HV3x