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.
Sequential
quaratusugene ozeplasmid
Biological/VaccineQuaratusugene ozeplasmid is an experimental non-viral immunogene therapy utilizing the TUSC2 gene, designed to target cancer cells by interrupting cell signaling pathways that allow cancer cells to grow, reestablishing pathways that promote cancer cell death and modulating the immune response against cancer cells.
osimertinib
DrugOsimertinib is a 3rd generation EGFR tyrosine kinase inhibitor (TKI) oral tablet administered daily, as indicated for treatment of patients with metastatic NSCLC whose tumors have EGFR genetic deletions or mutations.
Platinum-Based Chemotherapy
DrugCisplatin and carboplatin are intravenously administered platinum agents that are combined with other cytotoxic chemotherapy agents such as pemetrexed.
Recommended Phase 2 Dose (RP2D) - Phase 1
RP2D, which will be the maximum tolerated dose (MTD) or, if the MTD is not defined by the safety data, RP2D will be determined based on an integrated assessment of all available clinical safety and preliminary efficacy data.
Overall Response Rate (ORR) - Phase 2a
ORR (complete response \[CR\]+ partial response \[PR\]) according to RECIST using best overall response.
Progression-free Survival (PFS) - Phase 2b
PFS from randomization to disease progression or death. Response according to RECIST.
Progression-free Survival (PFS) - Phase 1
PFS from first dose to disease progression or death. Response according to RECIST.
Overall Response Rate (ORR) - Phase 1
ORR (CR+ PR) according to RECIST using best overall response.
Duration of Response (DOR) - Phase 1
DOR (CR + PR) from response to disease progression. Response according to RECIST.
Pharmacokinetics (PK) of Quaratusugene Ozeplasmid - Phase 1
Concentration of quaratusugene ozeplasmid in whole blood samples.
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