FDA Grants Orphan Drug Designation to Quratusugene Ozeplasmid for Small Cell Lung Cancer


The FDA has granted an orphan drug designation to quratusugene ozeplasmid (Reqorsa) for the treatment of patients with small cell lung cancer.



The FDA has granted an orphan drug designation to quratusugene ozeplasmid (Reqorsa) for the treatment of patients with small cell lung cancer (SCLC).1

In June 2023, the FDA granted fast track designation to quratusugene ozeplasmid for use in combination with atezolizumab (Tecentriq) in patients with extensive-stage SCLC (ES-SCLC) who did not develop disease progression following treatment with atezolizumab and chemotherapy in the first line.2 Quratusugene ozeplasmid also received fast track designations from the FDA in combination with osimertinib (Tagrisso) for patients with non–small cell lung cancer (NSCLC) whose disease has progressed after osimertinib treatment, and in combination with pembrolizumab (Keytruda) for patients whose disease has progressed following treatment with pembrolizumab.3,4

“We are excited to receive orphan drug designation from the FDA for [quratusugene ozeplasmid] for patients with SCLC,” Rodney Varner, president, chairman and chief executive officer at Genprex, said in a news release.1 “This FDA orphan drug designation in combination with our recently received FDA fast track designation underscores the great need for better treatment options for patients with SCLC, ES-SCLC and NSCLC. We look forward to initiating the [phase 1/2] ACCLAIM-3 clinical trial [NCT05703971] expected in the fourth quarter of 2023 in order to bring hope of an effective new therapy to patients suffering with this life-limiting cancer.”

Quratusugene ozeplasmid contains a plasmid that expresses the TUSC2 tumor suppressor gene protein. Tumor suppressor genes are deleted or inactivated early in the process of cancer development, rendering almost all patients with SCLC with reduced TUSC2 protein expression and 41% with no TUSC2 expression. However, preclinical data have shown that re-expressing TUSC2 may lead to clinical activity in mice, positioning quratusugene ozeplasmid as a potential treatment strategy for patients with median progression-free survival just over 5 months.1

The combination of quratusugene ozeplasmid and atezolizumab is being evaluated as maintenance therapy in patients with ES-SCLC without disease progression on standard frontline therapy with atezolizumab plus chemotherapy in the ongoing, open-label ACCLAIM-3 trial.

To be eligible for enrollment, patients must have completed 3 to 4 cycles of carboplatin, etoposide, and atezolizumab, achieving complete response, partial response, or stable disease. Upon enrollment, patients will receive the combination of atezolizumab and chemotherapy as maintenance therapy every 21 days until disease progression.

The phase 1 dose-escalation portion of the study is expected to enroll up to 12 patients at 3 to 5 clinical trial sites in the United States to determine the maximum tolerated dose of the combination. The highest dose evaluation will be the recommended phase 2 dose if no dose-limiting toxicities (DLTs) occur during phase 1. The phase 2 portion of the trial will enroll approximately 50 patients to between 5 and 10 sites.

The primary end point of the phase 2 portion of the trial is the 18-week progression-free survival rate from the start of maintenance therapy. A phase 2 futility analysis will also be performed after the 25th patient enrolled and treated reaches 18 weeks of follow up.

Earlier in 2023, investigators of the phase 1/2 ACCLAIM-1 trial (NCT04486833) received the green light from the safety review committee that the phase 2 portion of the trial evaluating quratusugene ozeplasmid in combination with osimertinib could proceed in patients with advanced EGFR-mutant NSCLC following progression on osimertinib.5

Findings from the dose-escalation portion of the study, which were presented at the 2023 ASCO Annual Meeting, demonstrated no DLTs among the 8 patients enrolled who received 0.06 mg/kg, 0.09 mg/kg, and 0.12 mg/kg of quratusugene ozeplasmid. Regarding safety, the most common adverse effects (AEs) were myalgia, pyrexia, chills, diarrhea, headache, influenza-like illness, and pain. The only grade 3/4 AEs were lymphopenia and neutropenia in 1 patient each.

Regarding efficacy, 1 patient at the 0.06 mg/kg dose level who had previously received carboplatin, pemetrexed (Alimta), and osimertinib experienced a partial remission (PR) by investigator assessment, and treatment was ongoing after 11 cycles. Another patient at the 0.09 mg/kg dose level, who had been previously treated with osimertinib, had stable disease and was in ongoing treatment after 9 cycles.6


  1. Genprex granted FDA orphan drug designation (ODD) for Reqorsa Immunogene therapy for the treatment of small cell lung cancer. News release. Genprex. August 10, 2023. Accessed August 14, 2023. https://www.genprex.com/news/genprex-granted-fda-orphan-drug-designation-odd-for-reqorsa-immunogene-therapy-for-the-treatment-of-small-cell-lung-cancer/
  2. 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. June 28, 2023. Accessed August 14, 2023. https://www.prnewswire.com/news-releases/genprex-receives-us-fda-fast-track-designation-for-reqorsa-immunogene-therapy-in-combination-with-tecentriq-for-the-treatment-of-small-cell-lung-cancer-301865443.html
  3. Genprex receives U.S. FDA fast track designation for gene therapy that targets lung cancer. News release. Genprex. January 21, 2020. Accessed August 14, 2023. https://www.genprex.com/news/genprex-receives-u-s-fda-fast-track-designation-for-gene-therapy-that-targets-lung-cancer/
  4. Genprex receives U.S. FDA fast track designation for Reqorsa Immunogene therapy in combination with Keytruda for the treatment of non-small cell lung cancer. News release. January 3, 2022. Accessed August 14, 2023. https://www.genprex.com/news/genprex-receives-u-s-fda-fast-track-designation-for-reqorsa-immunogene-therapy-in-combination-with-keytruda-for-the-treatment-of-non-small-cell-lung-cancer/
  5. Genprex receives safety review committee approval to advance to phase 2 expansion portion of Acclaim-1 clinical trial of Reqorsa in combination with Tagrisso in advanced non-small cell lung cancer. News release. Genprex. May 30, 2023. Accessed August 14, 2023. https://www.genprex.com/news/genprex-receives-safety-review-committee-approval-to-advance-to-phase-2-expansion-portion-of-acclaim-1-clinical-trial-of-reqorsa-in-combination-with-tagrisso-in-advanced-non-small-cell-lun/
  6. Berz D, Jotte RM, Pachipala KK, et al. ACCLAIM-1 dose escalation: determination of quaratusugene ozeplasmid and osimertinib recommended phase 2 dose (RP2D). J Clin Oncol. 2023;41(suppl 16):e15081. doi:10.1200/JCO.2023.41.16_suppl.e15081
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