Genprex’s NSCLC Immunogene Therapy Trial Cleared to Begin Phase 2 Expansion Portion

The phase 1/2 Acclaim-1 clinical trial (NCT04486833) evaluating quaratusugene ozeplasmid (Reqorsa), an investigational nonviral immunogene therapy intended to treat non–small cell lung cancer (NSCLC), in combination with the marketed epidermal growth factor receptor tyrosine kinase inhibitor osimertinib (Tagrisso; AstraZeneca) has received clearance from a safety review committee (SRC) composed of 3 of the trial’s principal investigators to initiate the phase 2 expansion portion.¹

In light of the SRC approval, Genprex announced that it anticipates initiating the phase 2 expansion portion of Acclaim-1 in Q3 2023. There have been no dose-limiting toxicities observed in the trial thus far; as such, the SRC has selected 0.12 mg/kg of Reqorsa, the highest dose used in the phase 1 part of the study, as the recommended phase 2 dose. Genprex will seek to enroll approximately 66 patients in the phase 2 expansion portion, with an equal number of patients assigned to 1 of 2 cohorts based on prior treatment history: 1 of these cohorts will enroll patients having been previously treated with osimertinib alone and the other will enroll patients having previously received treatment with both osimertiniband chemotherapy. The company is planning to perform an interim analysis after 19 patients in each cohort have been treated.

“We are proud of the notable progress we made during the phase 1 portion of the Acclaim-1 clinical trial, and the SRC recommendation to move into the phase 2 expansion portion of the trial is another validation for our Reqorsa development program,” Rodney Varner, the chairman, president, and CEO of Genprex, said in a statement.¹ “As we move into the phase 2 expansion portion of the trial, we remain steadfast in our efforts to bring new therapies to lung cancer patients with unmet medical need.”

Genprex will be presenting preliminary data from the phase 1 portion of Acclaim-1 at the American Society of Clinical Oncology (ASCO) 2023 Annual Meeting, held June 2-6, in Chicago, Illinois. According to the published abstract, among 8 patients treated with the combination therapy, 1 patient achieved a partial remission (PR) which remains ongoing.² This patient, who had been previously treated with carboplatin, pemetrexed, and osimertinib, was treated with 11 cycles of Reqorsa at the 0.06 mg/kg dose level. Another patient has maintained stable disease after being treated with 9 cycles of REQORSA at the 0.09 mg/kg dose level. This patient’s treatment history included prior treatment with osimertinib. Both of these patients are continuing treatment with Reqorsa.

The most common treatment-emergent adverse events (AEs) reported in the trial were myalgia, pyrexia, chills, diarrhea, headache, influenza-like illness, and pain. There were 2 grade 3 to grade 4 AEs in the study, which included lymphopenia in 1 patient and neutropenia in another patient. A postinfusion syndrome of myalgia, pyrexia, and chills that started 3 to 4 hours after administration of Reqorsa was observed. This was reported to resolve over the course of several hours following administration of acetaminophen and diphenhydramine therapy

“There was 1 PR with quaratusugene ozeplasmid and osimertinib combination therapy in the 8 patients enrolled in the phase 1 dose escalation, all of whom had progressed on osimertinib,” first author David Berz, MD, PhD, the founder of Valkyrie Clinical Trials, and colleagues wrote.² “Quaratusugene ozeplasmid was generally well tolerated, and was associated with a post-infusion syndrome of fever and chills managed with steroids, acetaminophen, and diphenhydramine.”

Genprex noted that the FDA has granted fast track designation to the combination therapy.¹ In addition to the phase 2 expansion portion, a phase 2 randomized portion for Acclaim-1 is also planned. This portion will seek to enroll approximately 74 patients, with half of the patients being randomly assigned to receive the combination therapy and the other half of the patients being randomly assigned to receive platinum-based chemotherapy. The company noted that progression-free survival will be utilized as the primary end point for this portion.

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REFERENCES
1. 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 June 1, 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/
2. Berz D, Jotte RM, Pachipala KK, Spira AI, Berger MS. ACCLAIM-1 dose escalation: Determination of quaratusugeneozeplasmid and osimertinib recommended phase 2 dose (RP2D). Presented at: the American Society of Clinical Oncology (ASCO) 2023 Annual Meeting, held June 2-6, in Chicago, Illinois. Abstract #e15081