Lung Cancer Immunogene Therapy Reqorsa Gets Its Third Fast Track Designation

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

Reqorsa is delivered intravenously and consists of a plasmid expressing the tumor suppressor gene TUSC2 encapsulated in a lipid nanoparticle. Reqorsa will be evaluated in combination with Tecentriq in the phase 1/2 Acclaim-3 clinical trial (NCT05703971), which will enroll patients who have achieved a complete response, partial response, or stable disease following an initial treatment regimen consisting of 3 to 4 cycles of carboplatin, etoposide, and Tecentriq. Genprex anticipates that Acclaim-3 will begin enrolling patients in Q3 2023; until they experience disease progression or unacceptable toxicity, participants in the trial will be treated with the Reqorsa and Tecentriq combination therapy every 21 days. The new fast track designation is the third to be granted by the FDA for a combination therapy involving Reqorsa; the agency previously granted fast track designations for Reqorsa in late-stage non–small cell lung cancer (NSCLC) indications: 1 for a combination therapy with epidermal growth factor receptor tyrosine kinase inhibitor Tagrisso (AstraZeneca) in patients whose disease progressed after being treated with Tagrisso and 1 for a combination therapy with PD1 antibody Keytruda (Merck) in patients whose disease progressed after being treated with Keytruda.

"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, the president, chairman, and chief executive officer of Genprex, said in a statement.¹ "This is another exciting achievement in our Reqorsa development program, which further validates Reqorsa ‘s potential not only in 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."

Acclaim-3 will begin with a dose escalation portion that will seek to recruit a maximum of 12 patients across 3 to 5 locations in the United States. Following determination of the recommended phase 2 dose, Acclaim-3's phase 2 portion will seek to recruit approximately 50 patients across 5 to 10 locations with the intention of assessing the 18-week progression-free survival (PFS) rate. In addition, the phase 2 portion will also evaluate survival and includes a futility analysis to be carried out when the 25th patient to be enrolled reaches their week 18 follow-up.

Acclaim-3 is 1 of 3 currently ongoing clinical trials evaluating Reqorsa. Genprex’s phase 1/2 Acclaim-1 clinical trial (NCT04486833), which is evaluating Reqorsa in combination with Tagrisso, recently received clearance from a safety review committee (SRC) composed of 3 of the trial’s principal investigators to initiate the phase 2 expansion portion.² In light of the SRC approval, Genprex announced that it anticipates initiating the phase 2 expansion portion of Acclaim-1 in Q3 2023. Meanwhile, Genprex’s phase 1/2 Acclaim-2 clinical trial (NCT05062980), which began enrolling patients in April 2022, is evaluating Reqorsa in combination with Keytruda.³ Notably, earlier this month Genprex received a patent covering the use of Reqorsa with PD1 antibodies in China to its repertoire of patents covering the Keytruda combination therapy in countries including the United States, Japan, Australia, Russia, and Mexico.⁴

“This fast track designation for the Acclaim-3 patient population is another validation of Reqorsa’s potential to treat lung cancer,” Mark Berger, MD, the chief medical officer of Genprex, added to the statement.¹ “We are very excited to soon begin treating patients in the Acclaim-3 clinical trial, which positions Reqorsa as a component of initial standard therapy for SCLC rather than as treatment for relapse. That will allow us to highlight the contribution of Reqorsa to an earlier stage of treatment. Based on our experience in other Reqorsa trials, we have reduced the phase 1 portion of the study to 2 dose levels instead of the 3 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 Tecentriq maintenance treatment will also shorten the time needed to evaluate the combination of Reqorsa and Tecentriq as maintenance therapy for 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 July 17, 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. 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 July 17, 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/
3. 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 July 17, 2023.https://www.obroncology.com/news/genprex-announces-the-opening-for-enrollment-of-its-phase-1-2-acclaim-2
4. Genprex granted Chinese patent for REQORSA immunogene therapy in combination with PD-1 antibodies to treat cancers. News release. Genprex, Inc. July 5, 2023. Accessed July 17, 2023. https://www.genprex.com/news/genprex-granted-chinese-patent-for-reqorsa-immunogene-therapy-in-combination-with-pd-1-antibodies-to-treat-cancers/