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

Inclusion Criteria:

1. Age ≥18 years.

2. Histologically or cytologically documented NSCLC.

3. Stage III or IV NSCLC or recurrent NSCLC that is not potentially curable byradiotherapy or surgery.

4. The NSCLC must be epidermal growth factor receptor (EGFR) mutation positive-positivebased on results from most recent tissue biopsy or most recent evaluation ofcirculating tumor DNA.

5. Achieved clinical response to osimertinib for ≥4 months, which can be a response ofstable disease. Must have a minimum of a 10-day osimertinib washout completed at thetime of enrollment.

6. Must have radiological progression on osimertinib treatment and can have eitherasymptomatic disease or symptomatic disease. In addition:

7. Must have measurable disease per RECIST 1.1.

8. Must have progression on osimertinib treatment as a single agent or incombination with other anti-cancer agents as their most recent treatment. Notes:

• Patients may have had treatment with other EGFR inhibitors as single agentsprior to osimertinib.

• Patients may have progression on osimertinib treatment being used for adjuvanttherapy after surgery.

7. Eastern Cooperative Oncology Group performance status (ECOG PS) score from 0 to 1.

8. Must be ≥28 days beyond major surgical procedures such as thoracotomy, laparotomy,or joint replacement and must not have evidence of wound dehiscence, active woundinfection, or comparable major residual complications of the surgery perInvestigator assessment.

9. Asymptomatic brain metastases must meet ALL criteria of the following (a-d):

10. No history of seizures in the preceding six months.

11. Definitive treatment must be completed ≥21 days.

12. Must be off steroids administered because of brain metastases or relatedsymptoms for ≥7 days.

13. Post-treatment imaging must demonstrate stability or regression of the brainmetastases.

14. Must have and be willing to submit a prior tumor biopsy or undergo a biopsy duringScreening to obtain tumor tissue for submission to a central laboratory for IHCanalysis and FISH or qPCR testing.

15. Absolute neutrophil count (ANC) >1500/mm3, platelet count >100,000/mm3 within ≤28days.

16. Adequate renal function documented by serum creatinine of ≤1.5 mg/dL or calculatedcreatinine clearance >50 ml/min within ≤28 days.

17. Adequate hepatic function as documented by serum bilirubin <1.5 mg/dL and aspartateaminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 X upper limit ofnormal (ULN) within ≤28 days.

18. Stable cardiac condition with a left ventricular ejection fraction ≥40% within ≤28days.

19. If female of childbearing potential (FOCBP), must have negative serum pregnancy test (serum beta-human chorionic gonadotropin [β-hCG]) within ≤7 days.

20. FOCBP and non-sterile male patients with female partner(s) of childbearing potentialmust agree to use two forms of contraception including one highly effective and oneeffective method beginning ≥2 weeks prior to enrollment through four monthsfollowing the last dose of study treatment.

21. If male, must agree to no sperm donation during study treatment and for anadditional four months following the last dose of study treatment.

22. Must have voluntarily signed an informed consent in accordance with institutionalpolicies.

Exclusion Criteria:

1. Unable to tolerate osimertinib treatment, leading to early treatment discontinuationor prolonged/frequent dosage modifications as determined by the Investigator.

2. Received prior gene therapy.

3. Other genetic characteristics (such as ALK, ROS, BRAF V600E mutations) which makethem a candidate for treatment with other approved targeted therapies.

4. Received radiotherapy to the skull, spine, thorax, or pelvis within ≤30 days.

5. Active concurrent malignancies, i.e., cancers other than NSCLC that require systemictherapy.

6. Active systemic viral, bacterial, or fungal infection(s) requiring treatment.

7. Serious concurrent illness or psychological, familial, sociological, geographical,or other concomitant conditions that, in the opinion of the Investigator, would notpermit adequate follow-up and compliance with the study protocol.

8. History of myocardial infarction or unstable angina within ≤6 months.

9. Known human immunodeficiency virus (HIV) infection or has active hepatitisinfection.

10. Female who is pregnant or breastfeeding.