Genprex Garners Orphan Drug Designation for Lung Cancer Immunogene Therapy Reqorsa

Genprex’s quaratusugene ozeplasmid (Reqorsa), an investigational immunogene therapy intended to treat various forms of lung cancer, has been granted orphan drug designation by the FDA for the treatment of extensive-stage small cell lung cancer (ES-SCLC) in combination with Genentech's checkpoint inhibitor atezolizumab (Tecentriq) for patients who did not experience tumor progression following initial standard treatment with atezolizumab and chemotherapy.¹

Reqorsa previously received fast track designation (FTD) from the FDA for the same indication in July of 2023.² Genprex is planning to evaluate this combination treatment as a maintenance therapy in the open-label phase 1/2 Acclaim-3 clinical trial (NCT05703971). As of July 2023, Acclaim-3 was not yet recruiting patients, but the company stated at the time that recruitment was expected to begin within the third quarter of 2023. Dosing of the first patient with Reqorsa in the trial is anticipated in the fourth quarter of this year.¹ Participants will be administered the Reqorsa and atezolizumab combination therapy every 21 days until they experience disease progression or unacceptable toxicity occurs. Acclaim-3 will seek to recruit patients who have achieved a complete response, partial response, or stable disease after an initial treatment regimen consisting of 3 to 4 cycles of carboplatin, etoposide, and atezolizumab.

“We are excited to receive orphan drug designation from the FDA for Reqorsa for patients with SCLC,” Rodney Varner, the president, chairman, and chief executive officer of Genprex, said in a statement.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 non–small cell lung cancer (NSCLC). We look forward to initiating the Acclaim-3 clinical trial 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.”

The initial dose escalation portion planned for Acclaim-3 will enroll as many as 12 patients at up to 5 clinical trial sites in the United States. The phase 2 portion will enroll approximately 50 patients at up to 10 clinical trial sites to be treated at the recommended phase 2 dose. The primary end point for this portion is the 18-week progression-free survival (PFS) rate measured from the initiation of treatment with the maintenance therapy.

Reqorsa has received 3 FTDs from the FDA in total. In addition to the aforementioned FTD for the Reqorsa/atezolizumab combination, FTDs have been granted for 2 combinations aimed at treating NSCLC indications. These include the combination of Reqorsa and epidermal growth factor receptor tyrosine kinase inhibitor osimertinib (Tagrisso; AstraZeneca) in patients whose disease progressed after being treated with osimertinib and the combination of Reqorsa and PD1 antibody pembrolizumab (Keytruda; Merck) in patients whose disease progressed after being treated with Keytruda. The Reqorsa/ozeplasmid combination is currently being evaluated in the phase 1/2 Acclaim-1 clinical trial (NCT04486833) and the Reqorsa/pembrolizumab combination is being evaluated in the phase 1/2 Acclaim-2 clinical trial (NCT05062980).^3,4

Reqorsa is intended to restore expression of TUSC2, a tumor suppressor gene that has reduced or absent expression in nearly all SCLCs.¹ Delivered intravenously, it consists of a plasmid expressing TUSC2 encapsulated in a lipid nanoparticle. Preclinical mouse model research determined that restoring expression of TUSC2 could have a clinical impact.

REFERENCES
1. Genprex granted FDA orphan drug designation (ODD) for REQORSA® immunogene therapy for the treatment of small cell lung cancer. News release. Genprex, Inc. August 10, 2023. Accessed August 15, 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. Genprex, Inc. June 28, 2023. Accessed August 15, 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/
3. 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, Inc. May 30, 2023. Accessed August 15, 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/
4. Genprex announces the opening for enrollment of its phase 1/2 Acclaim-2 clinical trial of REQORSA immunogene therapy in combination with Keytruda to treat non-small cell lung cancer. News Release. Genprex Inc. March 31, 2022. Accessed August 15, 2023. https://www.obroncology.com/news/genprex-announces-the-opening-for-enrollment-of-its-phase-1-2-acclaim-2