Acclaim-1, Acclaim-2, and Acclaim-3 will evaluate Reqorsa in combination with osimertinib, pembrolizumab, and atezolizumab, respectively.
Genprex’s quaratusugene ozeplasmid (Reqorsa), an investigational immunogene therapy intended to treat various forms of lung cancer, is currently being assessed in 3 separate clinical trials: Acclaim-1 (NCT04486833), Acclaim-2 (NCT05062980), and Acclaim-3 (NCT05703971).1
Reqorsa is delivered intravenously and consists of a plasmid expressing the tumor suppressor gene TUSC2, which has reduced or absent expression in nearly all small cell lung cancers (SCLCs), encapsulated in a lipid nanoparticle.1,2 Preclinical mouse model research indicates that restoring expression of TUSC2 could have a clinical effect. Each of the 3 studies is evaluating Reqorsa as a combination therapy with a different FDA-approved 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). Acclaim-1 is expected to enroll approximately 158 patients aged 18 years and older with stage 3 or stage 4 NSCLC or recurrent NSCLC that does not have cure potential via radiotherapy or surgery. Participants are also required to have EGFR mutations and to have achieved a clinical response or state of stable disease via osimertinib for 4 months or more; a 10 or more-day washout of osimertinib is required at enrollment. Additional inclusion and exclusion criteria exist.
Acclaim-1's design consists of a phase 1 dose escalation portion, a phase 2a expansion portion focused on assessing safety and preliminary efficacy of the combination treatment, and a phase 2b portion that will randomly assign patients in a 1:1 ratio to receive either the combination treatment or control treatment with platinum-based chemotherapy. In June 2023, Genprex reported that a safety review committee composed of 3 of the trial’s principal investigators gave clearance to initiate the phase 2 expansion portion with 0.12 mg/kg of Reqorsa, the highest dose used in the phase 1 part of the study, selected as the recommended phase 2 dose (RP2D). Acclaim-1's primary outcome measures are the RP2D for phase 1, the overall response rate for phase 2a, and progression-free survival (PFS) for phase 2b. The study is recruiting in the US, including in California, Colorado, Maryland, Texas, and Virginia.
“We recently completed the phase 1 portion of our Acclaim-1 clinical trial evaluating Reqorsa in combination with Tagrisso for NSCLC,” Mark Berger, MD, the chief medical officer of Genprex and study director, said in a statement issued to CGTLive™. “We also recently reported positive preliminary clinical data from this trial, which showed that Reqorsa was generally well tolerated, and there were no dose-limiting toxicities. While the phase 1 portion of the clinical trial is designed primarily to assess safety, promising efficacy results were also observed, as there were several patients who were progressing on their previous therapy [who] experienced long periods of response or stable disease. We look forward to treating patients in the upcoming phase 2 portion of our study soon.”
The phase 1/2 Acclaim-2 clinical trial is assessing Reqorsa in combination with PD1 antibody Keytruda (pembrolizumab, Merck) in patients with NSCLC whose disease has progressed after being treated with Keytruda alone. Daniel Morgensztern, MD, a professor of medicine in the Division of Oncology, Section of Medical Oncology, at the Washington University School of Medicine in St. Louis is the study’s principal investigator. Acclaim-2 is expected to enroll 180 patients aged 18 years or older with locally advanced or metastatic NSCLC. Participants are required to have previously achieved clinical benefit with pembrolizumab or pembrolizumab/platinum-based chemotherapy and experienced progression later on. Additional inclusion and exclusion criteria exist.
Similar to Acclaim-1, Acclaim-2's design consists of a phase 1 dose escalation portion, a phase 2 dose expansion portion, and a phase 2 randomized portion. The 3+3 dose escalation phase will treat patients at doses of 0.06 mg/kg, 0.09 mg/kg, and 0.12 mg/kg and a fixed dose of pembrolizumab at 200 mg. Patients will be treated in 21-day treatment cycles. The dose expansion portion will treat 36 patients at the RP2D to further assess safety and preliminary efficacy of the combination therapy. The randomized portion will randomly assign patients in a 2:1 ratio to receive either the combination therapy at the RP2D or a control treatment consisting of docetaxel with ramucirumab, docetaxel without ramucirumab, or a different FDA-approved treatment regimen chosen by the investigator. Acclaim-2's primary outcome measures are the RP2D for phase 1, PFS rate at 18 weeks post-treatment initiation for phase 2a, and PFS from random assignment to disease progression or death for phase 2b. The study is recruiting in the US, including Florida, Texas, and Missouri.
The phase 1/2 Acclaim-3 clinical trial is evaluating Reqorsa in combination with Genentech's checkpoint inhibitor Tecentriq (atezolizumab) for patients with extensive stage (ES)-SCLC who have not experienced tumor progression following initial standard treatment with Tecentriq and chemotherapy. Berger again serves as the study director. It is expected to enroll approximately 62 patients aged 18 years or older with a documented history of histologically or cytologically confirmed ES-SCLC. The trial will include 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. Additional inclusion and exclusion criteria exist.
Acclaim-3 consists of a phase 1 dose escalation portion and a phase 2 portion that will further assess the combination therapy at the RP2D. Unlike Acclaim-1 and Acclaim-2, there is no randomized portion assessing the experimental combination against a control included in the study’s design. The primary end point of the phase 1 portion is the RP2D and the primary end point of the phase 2 portion is the PFS rate at 18 weeks from treatment initiation. Acclaim-3 will use the combination treatment as maintenance therapy that patients will continue to receive in 21-day cycles until they experience disease progression or unacceptable toxicity. Genprex has announced that enrollment in Acclaim-3 is expected to initiate in the third quarter of 2023.
“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,” Berger said in a press release.1 “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 phase1 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.”