FDA Grants FTD to Quaratusugene Ozeplasmid Plus Atezolizumab in ES-SCLC

• This fast track designation (FTD) for quaratusugene ozeplasmid (Reqorsa) for the Acclaim-3 (NCT05703971) patient population supports the agent's potential to treat lung cancer.

• This marks the third fast track designation granted to quaratusugene ozeplasmid for patients, this time for patients with extensive-stage small cell lung cancer (ES-SCLC).

• The phase 1/2 Acclaim-3 study of quaratusugene ozeplasmid plus atezolizumab (Tecentriq) plans to enroll its first patient with ES-SCLC in the third quarter of 2023.

The FDA has granted fast track designation to quaratusugene ozeplasmid in combination with atezolizumab for the treatment of patients with ES-SCLC who did not develop tumor progression after receiving atezolizumab and chemotherapy as initial standard treatment, according to Genprex, Inc.¹

Quaratusugene ozeplasmid targets the TUSC2 gene and is designed to be injected intravenously into tumor cells to interrupt cell signaling pathways and recreate pathways for apoptosis in cancer cells. Quaratusugene ozeplasmid also modulates the immune response against cancer cells and blocks the development of drug resistance.²

Previously, the FDA has granted 2 FTDs for quaratusugene ozeplasmid, including quaratusugene ozeplasmid in combination with osimertinib (Tagrisso) in patients with late-stage non–small cell lung cancer (NSCLC) whose disease progressed after treatment with osimertinib, and for the combination of quaratusugene ozeplasmid and pembrolizumab (Keytruda) in patients with late-stage NSCLC whose disease progressed after treatment with pembrolizumab.¹

"This fast track designation for the Acclaim-3 patient population is another validation of [quaratusugene ozeplasmid’s] potential to treat lung cancer," said Mark Berger, MD, chief medical officer at Genprex, in a press release. "We are very excited to soon begin treating patients in the Acclaim-3 clinical trial, which positions [quaratusugene ozeplasmid] as a component of initial standard therapy for SCLC rather than as treatment for relapse. That will allow us to highlight the contribution of [quaratusugene ozeplasmid] to an earlier stage of treatment. Based on our experience in other [quaratusugene ozeplasmid] trials, we have reduced the phase 1 portion of the study to two dose levels instead of the three dose levels in our Acclaim-1 and Acclaim-2 clinical trials. We believe this will shorten the phase 1 portion of the trial.In addition, the median PFS of only 2.6 months seen with [atezolizumab] maintenance treatment will also shorten the time needed to evaluate the combination of [quaratusugene ozeplasmid and atezolizumab] as maintenance therapy for SCLC."

Image Credit: © appledesign [stock.adobe.com]

Now, the dose-escalation, phase 1/2 and clinical response study, Acclaim-3, is evaluating the combination of quaratusugene ozeplasmid and atezolizumab in patients with ES-SCLC.¹

The Acclaim-3 trial will enroll patients after they have received initial treatment with 3-4 cycles of carboplatin, etoposide, and atezolizumab, and achieve complete response, partial response, or stable disease. Following this, patients will be given treatment with quaratusugene ozeplasmid and atezolizumab as maintenance therapy every 21 days until disease progression.

In the phase 1 dose-escalation portion of the Acclaim-3 trial, up to 12 patients are planned to be enrolled at 3-5 clinical sites in the United States. This portion of the trial aims to determine the maximum tolerated dose (MTD) of the combination. If no dose limiting toxicities occur during this portion of the trial, the highest dose evaluated will be the recommended phase 2 dose. Then, the phase 2 portion of the study will enroll approximately 50 patients at 5-10 sites in the United States who will be treated with the combination until disease progression or unacceptable toxicity is experienced.

Patients will be eligible for enrollment in the study if aged 18 years and older with histologically or cytologically confirmed ES-SCLC, an ECOG performance status of 0-1, adequate renal and hepatic function, stable cardiac condition with a left ventricular ejection fraction ≥40% within ≤21 days, and an absolute neutrophil count >1500/mm3, platelet count >100,000/mm3 within ≤21 days.³ Patients must be ≥28 days beyond major surgical procedures and must be ≥10 days beyond minor surgical procedures, and must not have evidence of wound dehiscence, active wound infection, or comparable major residual complications of the surgery per investigator assessment.

Additionally, asymptomatic brain metastases must meet all criteria, including having no history of seizures in the preceding 6 months, definitive treatment must be completed ≥21 days prior to enrollment, steroids must have been completed if given because of brain metastases or related symptoms for ≥7 days, and if patients had previous brain irradiation, post-treatment imaging must demonstrate stability or regression of the brain metastases.

For the phase 2 portion of the trial, the primary end point is to determine the 18-week PFS rate from the time of the start of maintenance therapy with the combination in patients with ES-SCLC. Secondary end points are PFS, pharmacokinetics, and overall survival.3 After the 25th patient enrolled and treated in the study reaches 18 weeks of follow-up, a phase 2 futility analysis will be performed.¹

The first patient is expected to be enrolled into the phase 1/2 Acclaim-3 trial in the third quarter of 2023.

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

REFERENCES:

1. Genprex receives U.S. 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 29, 2023. https://tinyurl.com/ys5esepp

2. Genprex announces first patient dosed in phase 1/2 Acclaim-1 clinical trial of Reqorsa™ immunogene therapy in combination with Tagrisso® to treat non-small cell lung cancer. News release. March 2, 2022. Accessed June 29, 2023. https://bit.ly/35MdYkD

3. Quaratusugene ozeplasmid (Reqorsa) and atezolizumab maintenance therapy in ES-SCLC patients (Acclaim-3). ClinicalTrials.gov. Updated March 24, 2023. Accessed June 29, 2023. https://classic.clinicaltrials.gov/ct2/show/NCT05703971