The purpose of this randomized study is to determine the safety and efficacy of quaratusugene ozeplasmid (Reqorsa) added to osimertinib in NSCLC patients with activating EGFR mutations who have progressed while on treatment with osimertinib. Quaratusugene ozeplasmid consists of non-viral lipid nanoparticles that encapsulate a DNA plasmid with the TUSC2 tumor suppressor gene and is the first systemic gene therapy for cancer.
The study is comprised of a Phase 1 dose escalation portion and two Phase 2 portions evaluating safety and efficacy. Enrollment in the Phase 1 dose escalation portion is complete and the recommended Phase 2 dose (RP2D) was determined. Phase 2a has initiated and enrolled patients are treated with quaratusugene ozeplasmid at the RP2D in combination with osimertinib. In Phase 2b, patients will be randomized to receive either quaratusugene ozeplasmid plus osimertinib or platinum-based chemotherapy.
Age ≥18 years.
Histologically or cytologically documented NSCLC.
Stage III or IV NSCLC or recurrent NSCLC that is not potentially curable by radiotherapy or surgery.
The NSCLC must be epidermal growth factor receptor (EGFR) mutation positive-positive based on results from most recent tissue biopsy or most recent evaluation of circulating tumor DNA.
Unable to tolerate osimertinib treatment, leading to early treatment discontinuation or prolonged/frequent dosage modifications as determined by the Investigator.
Received prior gene therapy.
Other genetic characteristics (such as ALK, ROS, BRAF V600E mutations) which make them a candidate for treatment with other approved targeted therapies.
Received radiotherapy to the skull, spine, thorax, or pelvis within ≤30 days.