FDA Grants Fast Track Status to Quaratusugene Ozeplasmid Plus Atezolizumab in ES-SCLC

The FDA has granted fast track designation to the combination of quaratusugene ozeplasmid (Reqorsa) and atezolizumab (Tecentriq) as maintenance therapy in patients with extensive-stage small cell lung cancer (ES-SCLC) whose disease did not progress after receiving initial standard treatment with atezolizumab and chemotherapy.¹

The immunogene therapy is comprised of the TUSC2 gene encapsulated in a nanoparticle created from lipid molecules that have a positive electrical charge.² The drug is administered intravenously, target cancer cells, and once absorbed in those cells, expresses the TUSC2 gene into a protein that can reinstate select defective functions that occur in those cells.

Through its unique mechanism of action, the agent disrupts cell-signaling pathways that result in the proliferation of cancer cells and re-establish pathways for apoptosis in those cells. The agent has been shown to modulate immune responses against cancer cells and to block drug resistance mechanisms.

The combination is under evaluation in patients with ES-SCLC as part of the phase 1/2 Acclaim-3 trial (NCT05703971).^1,3 Genprex, Inc., the drug developer, shared that the first patient is expected to enroll to the trial in the third quarter of 2023.¹

“We are very pleased to receive a third fast track designation from the FDA for Reqorsa, this time for patients with ES-SCLC in combination with the checkpoint inhibitor Tecentriq,” Rodney Varner, president, chairman, and chief executive officer of Genprex, Inc., stated in a press release. “This is another exciting achievement in our Reqorsa development program, which further validates Reqorsa’s potential not only in non–small cell lung cancer [NSCLC] but also in SCLC. We look forward to accelerating the clinical development of Reqorsa, and potentially providing a new treatment option for patients with SCLC.”

The open-label, multicenter, phase 1/2 study will enroll patients with histologically or cytologically confirmed ES-SCLC before beginning treatment with atezolizumab, carboplatin, and etoposide.³ Patients will need to achieve a complete response, partial response, or stable disease following 3 to 4 cycles. Other inclusion criteria include having an ECOG performance status of 0 to 1, acceptable renal and hepatic function, stable cardiac condition, and an absolute neutrophil count of greater than 1500/mm³ as well as a platelet count of greater than 100,000/mm³ within 21 days.

Patients could not have previously received gene therapy or prophylactic cranial irradiation. They could not have active systemic viral, bacterial, or fungal infections in need of treatment, nor could they have serious concurrent illness or a history of autoimmune disease in need of immunosuppressing treatment.

After receiving initial treatment with atezolizumab, carboplatin, and etoposide, participants will receive quaratusugene ozeplasmid and atezolizumab as maintenance treatment.

The dose-escalation portion of the trial, which will enroll up to 12 patients, will examine up to 2 sequential dose-selection cohorts who will receive quaratusugene ozeplasmid at a starting dose of 0.09 mg/kg and 0.12 mg/kg given plus atezolizumab at 1200 mg once every 21 days.^1,3 Treatment will continue until progressive disease or intolerable toxicity.

Here, investigators will identify the maximum tolerated dose. If no dose-limiting toxicities are observed in this phase of the trial, then the highest dose examined will be established as the recommended phase 2 dose (RP2D).

In the phase 2 portion of the research, which is anticipated to enroll about 50 patients, participants will receive quaratusugene ozeplasmid at the RP2D and atezolizumab at 1200 mg once every 21 days until disease progression or intolerable toxicity. The key objective will be 18-week progression-free survival rate from the initiation of maintenance treatment with the combination.

A futility analysis will be conducted after the twenty-fifth patient is enrolled and has at least 18 weeks of follow-up.¹

Previously, the FDA granted fast track designations to quaratusugene ozeplasmid in combination with osimertinib (Tagrisso) for patients with late-stage NSCLC whose disease progressed following osimertinib, and to quaratusugene ozeplasmid plus pembrolizumab (Keytruda) for patients with late-stage NSCLC who had progressive disease following pembrolizumab.

References

1. Genprex receives US FDA fast track designation for Reqorsa Immunogene therapy in combination with Tecentriq for the treatment of small cell lung cancer. News release. Genprex, Inc. June 28, 2023. Accessed June 28, 2023. https://www.genprex.com/news/genprex-receives-u-s-fda-fast-track-designation-for-reqorsa-immunogene-therapy-in-combination-with-tecentriq-for-the-treatment-of-small-cell-lung-cancer/
2. Reqorsa Immunogene therapy: the first systemically delivered gene therapy used for cancer in humans. Genprex, Inc. website. Accessed June 28, 2023. https://www.genprex.com/technology/reqorsa/
3. Quaratusugene ozeplasmid (Reqorsa) and atezolizumab maintenance therapy in ES-SCLC patients (Acclaim-3). ClinicalTrials.gov. Updated March 24, 2023. Accessed June 28, 2023. https://classic.clinicaltrials.gov/ct2/show/NCT05703971