Combining gene therapy with osimertinib for advanced lung cancer patients

A Phase 1/2 Open-Label, Dose-Escalation and Clinical Response Study of Quaratusugene Ozeplasmid in Combination With Osimertinib in Patients With Advanced, Metastatic EGFR-Mutant, Metastatic Non-Small Cell Lung Cancer

This study is testing a new gene therapy combined with osimertinib to see if it can help people with advanced lung cancer who haven't responded to their current treatment.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 158 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Genprex, Inc. (Industry-sponsored)
• Drugs / interventions: osimertinib, chemotherapy, radiation
• Locations: 10 sites (Los Angeles, California and 9 other locations)
• Trial ID: NCT04486833 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the safety and efficacy of quaratusugene ozeplasmid (Reqorsa) in combination with osimertinib for patients with advanced non-small cell lung cancer (NSCLC) who have progressed on osimertinib. The study includes a Phase 1 dose escalation to determine the recommended dose and two Phase 2 portions to assess safety and efficacy. Patients will be randomized to receive either the investigational combination or platinum-based chemotherapy. The trial aims to provide insights into the potential of gene therapy in enhancing treatment outcomes for NSCLC patients.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with advanced NSCLC that is EGFR mutation positive and who have shown a clinical response to osimertinib for at least four months.

Not a fit: Patients who have not progressed on osimertinib or those with NSCLC that is not EGFR mutation positive may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could offer a new treatment option that improves outcomes for patients with advanced lung cancer who have limited options after progression on osimertinib.

How similar studies have performed: While gene therapy approaches are emerging, this specific combination of quaratusugene ozeplasmid with osimertinib is novel and has not been extensively tested in prior studies.

Eligibility criteria

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 by radiotherapy or surgery.
4. 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.
5. Achieved clinical response to osimertinib for ≥4 months, which can be a response of stable disease. Must have a minimum of a 10-day osimertinib washout completed at the time of enrollment.
6. Must have radiological progression on osimertinib treatment and can have either asymptomatic disease or symptomatic disease. In addition:

   1. Must have measurable disease per RECIST 1.1.
   2. Must have progression on osimertinib treatment as a single agent or in combination with other anti-cancer agents as their most recent treatment.

   Notes:
   * Patients may have had treatment with other EGFR inhibitors as single agents prior to osimertinib.
   * Patients may have progression on osimertinib treatment being used for adjuvant therapy 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 wound infection, or comparable major residual complications of the surgery per Investigator assessment.
9. Asymptomatic brain metastases must meet ALL criteria of the following (a-d):

   1. No history of seizures in the preceding six months.
   2. Definitive treatment must be completed ≥21 days.
   3. Must be off steroids administered because of brain metastases or related symptoms for ≥7 days.
   4. Post-treatment imaging must demonstrate stability or regression of the brain metastases.
10. Must have and be willing to submit a prior tumor biopsy or undergo a biopsy during Screening to obtain tumor tissue for submission to a central laboratory for IHC analysis and FISH or qPCR testing.
11. Absolute neutrophil count (ANC) \>1500/mm3, platelet count \>100,000/mm3 within ≤28 days.
12. Adequate renal function documented by serum creatinine of ≤1.5 mg/dL or calculated creatinine clearance \>50 ml/min within ≤28 days.
13. Adequate hepatic function as documented by serum bilirubin \<1.5 mg/dL and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 X upper limit of normal (ULN) within ≤28 days.
14. Stable cardiac condition with a left ventricular ejection fraction ≥40% within ≤28 days.
15. If female of childbearing potential (FOCBP), must have negative serum pregnancy test (serum beta-human chorionic gonadotropin \[β-hCG\]) within ≤7 days.
16. FOCBP and non-sterile male patients with female partner(s) of childbearing potential must agree to use two forms of contraception including one highly effective and one effective method beginning ≥2 weeks prior to enrollment through four months following the last dose of study treatment.
17. If male, must agree to no sperm donation during study treatment and for an additional four months following the last dose of study treatment.
18. Must have voluntarily signed an informed consent in accordance with institutional policies.

Exclusion Criteria:

1. Unable to tolerate osimertinib treatment, leading to early treatment discontinuation or 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 make them 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 systemic therapy.
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 not permit 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 hepatitis infection.
10. Female who is pregnant or breastfeeding.

Where this trial is running

Los Angeles, California and 9 other locations

• Valkyrie Clinical Trials — Los Angeles, California, United States (Recruiting)
• Rocky Mountain Cancer Centers — Lone Tree, Colorado, United States (Recruiting)
• Carle Cancer Institute — Urbana, Illinois, United States (Recruiting)
• Markey Cancer Center — Lexington, Kentucky, United States (Recruiting)
• Maryland Oncology Hematology — Rockville, Maryland, United States (Recruiting)
• The Valley Hospital - Luckow Pavilion — Paramus, New Jersey, United States (Recruiting)
• Gabrail Cancer Center Research — Canton, Ohio, United States (Recruiting)
• Millennium Oncology — Houston, Texas, United States (Terminated)
• Virginia Cancer Specialists — Fairfax, Virginia, United States (Recruiting)
• Virginia Oncology Associates — Norfolk, Virginia, United States (Recruiting)

Study contacts

• Study coordinator: Sr Director, Clinical Operations

Conditions Carcinoma, Non-Small Cell Lung; Epidermal growth factor receptor mutation; osimertinib; Tumor suppressor gene 2; Lipid nanoparticle; Gene therapy; Tagrisso; FUS1-nanoparticles