TUSC2-nanoparticles (GXP-001) in Combination With Pembrolizumab in Previously Treated Non-small Lung Cancer

• Status: Not yet recruiting
• Trial end date: 2025-12-01
• Target enrollment: 0
• Participant gender: All

Summary

The purpose of this randomized study is to determine the safety and efficacy of GPX-001 a.k.a REQORSA ( a TUSC2, tumor suppressor gene, encapsulated by non-viral lipid nanoparticles) in combination with pembrolizumab in patients with previously treated NSCLC.

The study will be conducted in 2 phases, a Dose Escalation Phase (Phase 1) and an Expansion Phase (Phase 2). In Phase 1, patients will be enrolled in sequential cohorts treated with successively higher doses of GXP-001 in combination with pembrolizumab.

In Phase 2, patients will be randomized to receive GXP-001 with pembrolizumab or docetaxel +/- ramucirumab (active comparator).

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Genprex, Inc.
• Treatments: Docetaxel; Pembrolizumab; Ramucirumab

Criteria

Inclusion Criteria:

1. Adults ≥ 18 years of age.

2. Voluntarily signed an informed consent in accordance with institutional policies.

3. Histologically or cytologically documented NSCLC with locally advanced or metastatic stage IV disease. Note: Any level of PD-L1 TPS is allowed.

4. Achieved clinical benefit to prior pembrolizumab/platinum-based chemotherapy for at least 3 months and subsequently progressed with radiological tumor assessment performed within 28 days of enrollment.

5. Eastern Cooperative Oncology Arm (ECOG) performance score from 0 to 1.

6. 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.

7. Demonstrate adequate organ function, as determined by the following laboratory values obtained within 7 days prior to enrollment:

1. Absolute neutrophil count (ANC) ≥ 1,500/μL,

2. Platelets ≥ 100,000/μL,

3. Hemoglobin ≥ 9.0 g/dL ≥ 4 weeks without transfusions,

4. International Normalized Ratio (INR) or Prothrombin Time (PT): ≤ 1.5 × upper limit of normal (ULN) unless the patient is receiving anticoagulant therapy as long as PT is within therapeutic range of intended use of anticoagulants,

5. Activated Partial Thromboplastin Time (aPTT) or Partial Thromboplastin Time (PTT): ≤ 1.5 × ULN unless the patient is receiving anticoagulant therapy as long as aPTT is within therapeutic range of intended use of anticoagulants,

6. Creatinine ≤ 1.5 × ULN OR Calculated creatinine clearance (CrCl) ≥ 60 mL/min for patients with creatinine levels > 1.5 × ULN,

7. Serum total bilirubin ≤ 1.0 × ULN,

8. AST and ALT ≤ 1.5 × ULN,

9. Alkaline phosphatase ≤ 2.5 x ULN.

8. Stable cardiac condition with a left ventricular ejection fraction > 40%.

9. If treated, asymptomatic brain metastases are present, must meet ALL criteria listed (a-d):

1. No history of seizures in the preceding 6 months,

2. Definitive treatment must be completed ≥ 4 weeks prior to enrollment,

3. Stopped steroid treatments administered because of brain metastases or related symptoms for ≥ 2 weeks prior to enrollment,

4. Post-treatment imaging must demonstrate stability or regression of the brain metastases.

10. Female patients must have a negative serum pregnancy test at screening (within 7 days of enrollment) if of childbearing potential or be of non-childbearing potential.

11. Female patients of childbearing potential 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 4 months following the last dose of study treatment.

12. Male patients must agree to no sperm donation during study treatment and for an additional 4 months following the last dose of study treatment.

Exclusion Criteria:

1. Unable to tolerate pembrolizumab treatment, leading to early treatment discontinuation or prolonged/ frequent dosage modifications.

2. Hypersensitivity to docetaxel or polysorbate 80 (Phase 2 only)

3. Patients at risk of tumor lysis syndrome [e.g., renal impairment, hyperuricemia, bulky tumor (Phase 2 only)]

4. Received prior systemic chemotherapy or monoclonal antibodies for the treatment of the participant's advanced or metastatic disease within 1 month of study enrollment

5. Received prior gene therapy.

6. Received any radiotherapy to the skull, spine, thorax or pelvis within 1 month of study enrollment.

7. Expected to require any other form of antineoplastic therapy while participating in the study.

8. Received a live-virus vaccination within 1 month of planned treatment start. Seasonal flu vaccines that do not contain live virus are permitted.

9. Has known active CNS metastases and/or carcinomatous meningitis.

10. Active, known, or suspected autoimmune disease.

11. Active systemic viral, bacterial, or fungal infections(s) requiring treatment.

12. Serious concurrent illness or psychological, familial, sociological, geographical, or other condition that, in the opinion of the investigator, would prevent adequate follow-up and compliance with the study protocol.

13. A condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study enrollment. Inhaled or topical steroids and adrenal replacement doses ≤10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.

14. Active concurrent malignancies, i.e., cancers other than NSCLC.

15. Has a second, concurrent, untreated malignancy.

16. History of symptomatic interstitial lung disease or pneumonitis that required oral or IV glucocorticoids to assist with management.

17. History of myocardial infarction or unstable angina within the past 6 months.

18. Presence of pre-existing peripheral neuropathy that is ≥ Grade 2 by National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 (NCI-CTCAE) criteria.

19. Is, at the time of signing informed consent, a regular user (including "recreational use") of any illicit drugs or has a recent history (within the last year) of substance abuse (including alcohol) requiring medical intervention.

20. Known human immunodeficiency virus (HIV) infection or has active hepatitis infection.

21. Female patients who are pregnant or breastfeeding.