Phase 1 of the Acclaim-3 study evaluating quaratusugene ozeplasmid plus atezolizumab in patients with extensive-stage small cell lung cancer has enrolled and dosed its first patient.
Trial Name: A Phase 1/2 Clinical Trial of Quaratusugene Ozeplasmid and Atezolizumab Maintenance Therapy in Patients With Extensive Stage Small Cell Lung Cancer (ES-SCLC)
ClinicalTrials.gov Identifier: NCT05703971
Sponsor: Genprex, Inc.
Recruitment Contact: Sr Director, Clinical Operations, 1-877-774-GNPXkcombs@genprex.com, and Chief Medical Officer, 1-877-774-GNPXmberger@genprex.com
Completion Date: August 2027
3D rendered Medical Illustration of Male Anatomy - Lung Cancer:© Sebastian Kaulitzki- stock.adobe.com
The first patient with extensive-stage small cell lung cancer (ES-SCLC) has received treatment with the combination of quaratusugene ozeplasmid (Reqorsa) and atezolizumab (Tecentriq) in the phase 1, dose-escalation portion of the Acclaim-3 trial (NCT05703971).1
Acclaim-3 is an open-label, dose-escalation, clinical response, phase 1/2 study evaluating maintenance therapy of quaratusugene ozeplasmid plus atezolizumab in patients with ES-SCLC.
The study is enrolling patients after they receive initial treatment with 3 to 4 cycles of carboplatin, etoposide, and atezolizumab and achieve complete response, partial response, or stable disease.2 Patients will then be treated with quaratusugene ozeplasmid and atezolizumab as maintenance therapy every 21 days until disease progression.
"We are excited to take this next step in our fight against lung cancers as we work to advance an innovative therapy that we believe provides hope to patients suffering with ES-SCLC, an especially aggressive form of lung cancer that has extremely limited treatment options," said Ryan Confer, president and chief executive officer at Genprex, in a press release.1
"With a median progression-free survival [PFS] of 5.2 months, ES-SCLC has a particularly poor prognosis. Additionally, patients receiving [atezolizumab] as maintenance therapy have a median PFS of 2.6 months after the start of maintenance therapy. With such limited benefit from current treatments, we believe the combination of [quaratusugene ozeplasmid] and [atezolizumab] can provide a promising new therapeutic option for the treatment of small cell lung cancer," continued Confer.
Enrollment in the Acclaim-3 trial is open to patients who did not develop tumor progression after receiving treatment with atezolizumab and chemotherapy as standard initial treatment. Therefore, these patients are eligible for maintenance therapy.
In phase 1, the dose-escalation portion of the trial, up to 12 patients are expected to be enrolled at approximately 10 clinical sites across the US. Here, investigators seek to determine the maximum tolerated dose of the combination. If there are no dose-limiting toxicities observed during phase 1, the highest dose to be evaluated will serve as the recommended phase 2 dose.
Phase 2 then plans to include about 50 patients at 10 to 15 sites in the US who will be given the combination until disease progression or unacceptable toxicity. For phase 2, the primary end point is to determine the 18-week PFS rate from the time of the start of maintenance therapy with the combination in patients with ES-SCLC.
In addition, patients will be followed for survival, and once the 25th patient enrolled and treated with the combination reaches 18 weeks of follow-up, a phase 2 futility analysis will be performed. This portion of the study is expected to begin in the second half of 2024.
"The phase 1 dose-escalation portion of the Acclaim-3 study is expected to determine the maximum tolerated dose for the phase 2 expansion study," stated Mark Berger, MD, chief medical officer of Genprex, in a press release. "The favorable results from our phase 1 Acclaim-1 [NCT04486833] study in non-small cell lung cancer [NSCLC] enabled us to shorten the phase 1 portion of Acclaim-3. This should allow us to complete the phase 1 portion of the study during the second half of 2024 and to advance more quickly into the phase 2 expansion portion of Acclaim-3 in the second half of 2024. We look forward to providing study updates as we advance this potentially life-saving therapy to benefit patients battling ES-SCLC."
Quaratusugene ozeplasmid works by targeting the TUSC2 gene. The agent is designed as an intravenous injection to tumor cells which then interrupts cell signaling pathways and recreates pathways for apoptosis in cancer cells. Further, the agent modulates the immune response against cancer cells and blocks the development of drug resistance.
Previously in June 2023, the FDA granted a fast track designation to quaratusugene ozeplasmid in combination with atezolizumab for the treatment of patients with ES-SCLC who did not develop tumor progression after receiving atezolizumab and chemotherapy as initial standard treatment.
The FDA also granted other 2 fast track designations for quaratusugene ozeplasmid, including in combination with osimertinib (Tagrisso) in patients with late-stage NSCLC whose disease progressed after treatment with osimertinib and for the combination of quaratusugene ozeplasmid and pembrolizumab (Keytruda) in patients with late-stage NSCLC whose disease progressed after treatment with pembrolizumab.3
