Reqorsa (Quaratusugene Ozeplasmid) and Osimertinib in Patients With Advanced Lung Cancer Who Progressed on Osimertinib

Inclusion Criteria:

Histologically or cytologically documented non-small cell lung cancer (NSCLC).
Stage III or IV NSCLC or recurrent NSCLC that is not potentially curable by radiotherapy or surgery whether or not patient has received prior chemotherapy.
EGFR mutation-positive as detected by an FDA-approved test, based on results of most recent biopsy.
Achieved clinical response to osimertinib for ≥4 months.
Must have radiological progression on or after treatment with osimertinib and can have either asymptomatic disease or symptomatic disease. For Phase 2 only, eligibility for patients with symptomatic disease is restricted to those with limited metastasis (≤5 metastases).
Eastern Cooperative Oncology Arm (ECOG) performance score from 0 to 1.
Must be ≥28 days beyond major surgical procedures such as thoracotomy, laparotomy, or joint replacement, and must be ≥10 days beyond minor surgical procedures such as biopsy of subcutaneous tumors, pleuroscopy, etc., and must not have evidence of wound dehiscence, active wound infection, or comparable major residual complications of the surgery.

If asymptomatic brain metastases are present must meet ALL criteria listed:

No history of seizures in the preceding 6 months.
Definitive treatment must be completed ≥21 days.
Patients must be off steroids administered because of brain metastases or related symptoms for ≥7 days.
Post-treatment imaging must demonstrate stability or regression of the brain metastases.
ANC >1500/mm3, platelet count >100,000/mm3 within ≤21 days.
Adequate renal function documented by serum creatinine of ≤1.5 mg/dL or calculated creatinine clearance >50 ml/min within ≤21 days.
Adequate hepatic function as documented by serum bilirubin <1.5 mg/dL and AST and ALT ≤2.5 X upper limit of normal (ULN) within ≤21 days.
Stable cardiac condition with a left ventricular ejection fraction ≥40% within ≤21 days.
If female of childbearing potential, must have negative serum pregnancy test (serum β-hCG) within ≤7 days.
Must agree to 2 forms of contraception including 1 highly effective and 1 effective methods during the study period and for 4 months following the last dose of study treatment.
If male, must agree to no sperm donation during study treatment and for an additional 4 months following the last dose of study treatment.
Must have voluntarily signed an informed consent in accordance with institutional policies.

Exclusion Criteria:

Unable to tolerate osimertinib treatment, leading to early treatment discontinuation or prolonged/frequent dosage modifications.
Received standard chemotherapy or monoclonal antibodies to treat NSCLC within ≤21 days.
Received prior gene therapy.
Other genetic characteristics (such as ALK, ROS, BRAF V600E mutations) which makes them a candidate for treatment with other approved targeted therapies.
Received radiotherapy to the skull, spine, thorax, or pelvis within ≤30 days.
Active systemic viral, bacterial, or fungal infection(s) requiring treatment.
Serious concurrent illness or psychological, familial, sociological, geographical, or other concomitant conditions that, in the opinion of the investigator, would not permit adequate follow-up and compliance with the study protocol.
History of myocardial infarction or unstable angina within ≤6 months.
Known human immunodeficiency virus (HIV) infection or has active hepatitis infection.
Female who is pregnant or breastfeeding.