Acclaim-3 Trial Escalates Quaratusugene Ozeplasmid/Atezolizumab Dosing in SCLC

Small tumor cancer cells: © Yuriy - stock.adobe.com

The phase 1 dose-escalation portion of the Acclaim-3 trial (NCT05703971) evaluating quaratusugene ozeplasmid (Reqorsa) in combination with atezolizumab (Tecentriq) has successfully completed its 0.09 mg/kg dose cohort.¹ This study is investigating the combination as a maintenance therapy for the treatment of patients with extensive-stage small cell lung cancer (ES-SCLC).

Following a favorable safety profile in this initial cohort, the safety review committee (SRC) has authorized dose escalation to the highest planned dose of 0.12 mg/kg.

Quaratusugene ozeplasmid and atezolizumab have already received fast track designation from the FDA for their potential in treating the Acclaim-3 patient population, while quaratusugene ozeplasmid alone has an orphan drug designation in SCLC.

"We believe the SRC's recommendation to advance to the highest dose group of the phase 1 portion of the trial is another clinical validation for our [ozeplasmid] development program," said Ryan Confer, president and chief executive officer of Genprex, in a press release. "We are proud of the achievements so far in the phase 1 portion of the trial, which has demonstrated a favorable safety profile for [ozeplasmid] in the first trial to use [ozeplasmid] for [patients with] SCLC.”

To date, no dose-limiting toxicities have been observed among patients treated at the 0.09 mg/kg dose cohort. The SRC’s green light for dose escalation was based on these positive safety findings.

This group also included a patient who demonstrated a partial response after receiving this combination. This patient had a 30% decrease in tumor size on CT scans after 2 cycles of maintenance therapy. A subsequent scan after 4 cycles confirmed the same degree of tumor shrinkage in measurable lesions, although 1 previously unmeasurable lesion showed progression, ultimately leading to a conclusion of disease progression.

Additionally, the patient had already undergone 4 cycles of atezolizumab as part of their induction therapy, and responses to atezolizumab alone are typically observed earlier in treatment.

“We look forward to continuing to treat these patients while we work toward bringing new therapies to lung cancer patients with unmet medical need,” continued Confer.

Acclaim-3 Trial’s Study Design

Acclaim-3 is an open-label, multi-center, phase 1/2 study evaluating the combination of quaratusugene ozeplasmid and atezolizumab in patients with ES-SCLC who did not experience tumor progression after initial treatment with atezolizumab and chemotherapy.²

The phase 1 portion of the trial is now advancing to its 0.12 mg/kg dose cohort. This part of the study aims to establish the maximum tolerated dose or the recommended phase 2 dose of the combination. Patients will continue to be treated with the combination until disease progression or unacceptable toxicity occurs.

Once the dose-escalation phase of the study is completed, the phase 2 expansion portion will enroll 50 patients across 10 to 15 sites in the US. Here, investigators will primarily assess progression-free survival at 18 weeks posttreatment initiation, with a planned futility analysis after the first 25 patients reach 18-week follow-up. Patients will also be followed for overall survival.

The company anticipates completing enrollment for the 0.12 mg/kg dose cohort in the second half of 2024, followed by the initiation of phase 2 expansion part of the trial.¹

REFERENCES:

1. Genprex receives safety review committee approval to advance to highest dose group in phase 1 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. October 15, 2024. Accessed October 15, 2024. https://tinyurl.com/2p9x6y3t

2. Quaratusugene ozeplasmid (Reqorsa) and atezolizumab maintenance therapy in ES-SCLC patients (Acclaim-3). ClinicalTrials.gov. Updated May 20, 2024. Accessed October 15, 2024. https://classic.clinicaltrials.gov/ct2/show/NCT05703971