Genprex Makes Progress in 2 of 3 Lung Cancer Trials for Gene Therapy Reqorsa, but Drops the Other

Genprex has reported positive preliminary results from 2 trials, Acclaim-1 (NCT04486833) and Acclaim-3 (NCT05703971), evaluating combination treatments including quaratusugene ozeplasmid (Reqorsa), its investigational immunogene therapy intended to treat various forms of lung cancer.¹ On the other hand, the company has decided to discontinue Acclaim-2 (NCT05062980), its other trial for a Reqorsa combination treatment.

The phase 1/2 Acclaim-1 clinical trial is evaluating Reqorsa in combination with the marketed epidermal growth factor receptor tyrosine kinase inhibitor osimertinib (Tagrisso; AstraZeneca) for the treatment of non-small cell lung cancer (NSCLC). Genprex reported that 2 patients who are were treated in the phase 1 dose escalation portion of Acclaim-1, and are continuing to receive the combination therapy, have achieved long-term progression-free survival (PFS). One of these patients, who had previously been treated with Tagrisso and chemotherapy, achieved a partial response (PR) after receiving the second course of the trial’s combination therapy, and has maintained PFS for over 2 years since then. The other patient has had stable disease for over 15 months.

Alongside this update, Genprex also noted that it has scaled back the phase 2a expansion portion of Acclaim-1 to a single cohort that will aim to enroll approximately 33 patients who have had prior treatment with Tagrisso alone. A previously planned separate cohort for patients who have had prior treatment with both Tagrisso and chemotherapy has been eliminated from the protocol. The company cited resource prioritization and a desire to focus on patients most likely to benefit from Reqorsa as the motivation for the change. Genprex expects that it will have enrolled 19 patients in the phase 2a expansion portion by the first half of next year, at which point it will carry out an interim analysis.

Meanwhile, the phase 1/2 Acclaim-3 clinical trial is evaluating Reqorsa in combination with Genentech's checkpoint inhibitor Tecentriq (atezolizumab) as a maintenance therapy for patients with extensive stage (ES)-SCLC who have not experienced tumor progression following initial standard treatment with Tecentriq and chemotherapy. The first patient treated in Acclaim-3, who began receiving the combination therapy in May 2024, achieved a PR after the second cycle of Reqorsa/Tecentriq, according to CT scan results. A more recent CT scan, taken after 4 cycles of the combination therapy, indicates that a 30% reduction in tumor size for measurable lesions had been attained since the patient’s baseline CT scan that was taken after induction therapy. Although, a previously unmeasurable lesion had increased in size on this scan; as such, disease progression was determined to have occurred 3 months after the beginning of the combination therapy.

“This patient’s response was not expected during maintenance therapy with Tecentriq alone, and we believe these results are promising and a positive early indication for the study,” Mark Berger, MD, the chief medical officer of Genprex, said in a statement.¹ “Once ES-SCLC patients begin maintenance therapy with Tecentriq, median PFS is very short; only 2.6 months, and further tumor regression rarely occurs. The ES-SCLC patient in the Acclaim-3 clinical trial treated with our combination therapy experienced PR, but asymptomatic disease progression was diagnosed by CT scan 3 months after the start of maintenance therapy. We find this positive result to be promising, particularly because this patient was treated with the lower of 2 doses planned for the phase 1 portion of this clinical trial, and we are hopeful that the combination of REQORSA and Tecentriq will improve outcomes and help extend the lives of these very difficult to treat lung cancer patients.”

On the other hand, Genprex has decided to discontinue enrolling new patients in Acclaim-2, a phase 1/2 clinical trial evaluating Reqorsa in combination with PD1 antibody Keytruda (pembrolizumab, Merck) in patients with NSCLC whose disease has progressed after being treated with Keytruda alone. Genprex stated that a number of factors contributed to this decision, highlighting difficulties with enrolling patients related to competition with the many other ongoing clinical trials that are recruiting from the same patient population. The company noted that participants already being treated in Acclaim-2 will continue to receive treatment in the trial until disease progression occurs.

In addition to the aforementioned updates, Genprex also announced this month that it has received a patent from the Singapore Patent Office relating to the use of Reqorsa in combination with anti–PD-1 antibodies.² The patent, which provides coverage through 2037, joins patents the company has received for the gene therapy's use in combination with an immune checkpoint inhibitor in several other countries across the globe, including the United States, Japan, Mexico, Russia, Australia, Chile, China, and Korea.

“This patent expands our intellectual property portfolio, providing us with additional protection and exclusivity for our drug combinations with Reqorsa and furthering our patent protection in the Asian markets where lung cancer is the most prevalent,” Thomas Gallagher, Esq., the senior vice president of intellectual property and licensing at Genprex, said in a statement.²

CGTLive® previously covered the designs of the 3 Reqorsa trials in September 2023. Notably, all 3 combination therapy clinical programs have received fast track designation from the FDA, and the SCLC program has received an FDA orphan drug designation.^3,4

REFERENCES
1. Genprex Announces Positive Clinical Study Updates from Acclaim-1 and Acclaim-3 Phase 1/2 Clinical Trials in Lung Cancer. News release. Genprex, Inc. August 14, 2024. Accessed August 15, 2024. https://www.genprex.com/news/genprex-announces-positive-clinical-study-updates-from-acclaim-1-and-acclaim-3-phase-1-2-clinical-trials-in-lung-cancer/
2. Genprex Granted Patent in Singapore for Reqorsa® Gene Therapy with PD-1 Antibodies to Treat Cancers. News release. Genprex, Inc. August 13, 2024. Accessed August 15, 2024. https://www.genprex.com/news/genprex-granted-patent-in-singapore-for-reqorsa-gene-therapy-with-pd-1-antibodies-to-treat-cancers/
3. 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, 2024. 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/
4. 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, 2024. https://www.genprex.com/news/genprex-granted-fda-orphan-drug-designation-odd-for-reqorsa-immunogene-therapy-for-the-treatment-of-small-cell-lung-cancer/