Acclaim-3 Trial in SCLC Moves to Phase 2 After Positive Safety, Efficacy Data

Small cell lung cancer: © Констянтин Батыльчук- stock.adobe.com

The phase 1, dose-escalation portion of the Acclaim-3 trial (NCT05703971) evaluating quaratusugene ozeplasmid (Reqorsa) in combination with atezolizumab (Tecentriq) as maintenance therapy for the treatment of patients with extensive-stage small cell lung cancer (ES-SCLC) has been completed.¹

Full safety data from the trial showed that there were no dose limiting toxicities (DLTs) observed. The recommended phase 2 dose (RP2D) of quaratusugene ozeplasmid has been set at 0.12 mg/kg, which was marked as the highest dose level delivered in the phase 1 portion of the study.

With this, the safety review committee (SRC) has approved the start of the phase 2 expansion portion of the Acclaim-3 trial, and enrollment has now opened.

"We are pleased to complete the phase 1 dose escalation portion of the Acclaim-3 clinical trial and to have now opened the phase 2 expansion portion of Acclaim-3 for enrollment in the second half of 2024, in accordance with our previously disclosed guidance for timing and milestones," said Ryan Confer, president and chief executive officer at Genprex, in a press release. "Our partnership with a large network of community-based oncology practices has allowed us to have successful enrollment rates, enabling Genprex to meet our 2024 timeline targets for this study. In adding multiple clinical trial sites to our Acclaim-3 study, we have been able to more efficiently and expeditiously accelerate the Acclaim-3 clinical trial.”

Acclaim-3 is an open-label, multi-center, phase 1/2 trial evaluating the quaratusugene ozeplasmid gene therapy in combination with atezolizumab as maintenance therapy in patients with ES-SCLC who did not develop tumor progression after receiving atezolizumab and chemotherapy as initial standard treatment.²

Previously, this combination was granted fast track designation from the FDA in this patient population. Orphan drug designation from the FDA has also been granted to atezolizumab for the treatment of patients with SCLC.¹

In the phase 1, dose-escalation portion of the trial, up to 12 patients were enrolled at approximately 10 clinical sites across the US. Investigators sought to determine the maximum tolerated dose of the combination. Phase 2 of the study will include about 50 patients at 10 to 15 sites in the US. These patients will be given the combination until disease progression or unacceptable toxicity.²

For phase 2 of the study, the primary end point is to determine the 18-week progression-free survival rate from the time of the start of maintenance therapy with the combination in patients with ES-SCLC.

In the phase 1 dose-escalation portion of the Acclaim-3 trial, initial findings showed that the first patient treated achieved a partial remission, defined as a ≥30% reduction in tumor size from baseline after 2 cycles of maintenance therapy. A subsequent CT scan after 4 cycles of maintenance therapy confirmed a 30% decrease in measurable lesions. However, 1 lesion, which had not been measurable previously, showed growth, leading to disease progression at that time.

As the patient had already received 4 cycles of atezolizumab during induction therapy, with responses to atezolizumab expected earlier, these results suggest that quaratusugene ozeplasmid may provide a clinical benefit in this patient.

Based on the preliminary safety data from patients in the first portion of the study treated at the 0.12 mg/kg dose level, the SRC determined this dose to be the RP2D that will be used in the phase 2 portion of the trial.

“Looking ahead, we believe this sets the stage for potential promising enrollment rates for the phase 2 portion of the trial. Additionally, we will be submitting the results of the phase 1 portion of the study to a clinical meeting and anticipate data presentation in 2025, and we remain encouraged by the early efficacy demonstrated in [patients with] ES-SCLC," added Confer in the press release.¹

REFERENCES:

1. Genprex receives safety review committee approval to advance to phase 2 portion of Acclaim-3 clinical trial of reqorsa® gene therapy in combination with tecentriq® in extensive stage small cell lung cancer. News release. Genprex, Inc. December 16, 2024. Accessed December 16, 2024. https://tinyurl.com/38v36a5b

2. Quaratusugene ozeplasmid (Reqorsa) and atezolizumab maintenance therapy in ES-SCLC patients (Acclaim-3). ClinicalTrials.gov. Updated May 20, 2024. Accessed December 16, 2024. https://classic.clinicaltrials.gov/ct2/show/NCT05703971