TUSC2-nanoparticles (GPX-001) and Osimertinib in Patients With Stage IV Lung Cancer Who Progressed on Osimertinib Alone

• Status: Recruiting
• Trial end date: 2025-08-01
• 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, encapsulate by non-viral lipid nanoparticles) added to osimertinib in NSCLC patients with activating EGFR mutations who have progressed while on treatment with osimertinib.

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 GPX-001 in combination with osimertinib. In Phase 2, patient will be randomized to receive GPX-001 plus osimertinib or osimertinib alone.

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

Details

• Lead Sponsor: Genprex, Inc.
• Treatments: Osimertinib

Criteria

Inclusion Criteria:

• Histologically or cytologically documented Non-small Cell Lung Cancer (NSCLC)

• Stage 3 or 4 NSCLC or recurrent NSCLC that is not potentially curable by radiotherapy or surgery whether or not they have received prior chemotherapy

• EGFR mutation-positive as detected by an FDA-approved test

• Achieved a clinical response to osimertinib for at least 4 months

• Must have progressed on or after treatment with osimertinib either with asymptomatic disease or symptomatic disease with limited metastasis ( less than 5 metastases) prior to study entry

• Eastern Cooperative Oncology Arm performance score from 0 to 1

• Subjects must be ≥28 days beyond major surgical procedures such as thoracotomy, laparotomy or joint replacement, and must be ≥1.5 weeks 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. Note: placement of catheter is not considered minor surgery for this study.

• Subjects with asymptomatic brain metastases that have been treated are eligible if the following criteria are met:

• No history of seizures in the preceding 6 months.

• Definitive treatment must have been completed ≥21 days prior to start of study treatment.

• Subjects must be off steroids that were being administered because of brain metastases or related symptoms for ≥7 days prior to start of study treatment.

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

• ANC >1500/mm3, platelet count >100,000/mm3 ≤7 days of study treatment

• PT and PTT <1.25 times the upper limit of normal ≤7 days of study treatment

• Adequate renal function documented by serum creatinine of ≤1.5 mg/dl or calculated creatinine clearance >50 ml/min ≤7 days of study treatment

• Adequate hepatic function as documented by serum bilirubin <1.5 mg/dl and liver transaminases ≤2.5 X upper limit of normal ≤7 days of study treatment

• Stable cardiac condition with a left ventricular ejection fraction ≥40% within 21 days of study treatment

• If female and of childbearing potential, must have negative serum pregnancy test ≤7 days of study treatment (Note: non-childbearing is defined as greater than one year post- menopausal or surgically sterilized).

• Must agree to practice effective birth control (e.g., abstinence, intrauterine device for female subjects) during the study period.

• Must have voluntarily signed an informed consent in accordance with institutional policies.

Exclusion Criteria:

• Subject who did not tolerate osimertinib treatment, leading to early treatment discontinuation or prolonged/ frequent dosage modifications.

• Progressing subject who is symptomatic and have >5 metastasis

• Subject received standard chemotherapy or monoclonal antibodies to treat NSCLC within ≤21 days prior to study treatment.

• Subject received prior gene therapy.

• Subjects with other genetic characteristics which make them candidates for treatment with other approved targeted therapies, or prior treatment with checkpoint inhibitors

• Subject received radiotherapy to the skull, spine, thorax or pelvis within ≤30 days of start of study treatment. Subjects are permitted to have received palliative radiotherapy to an extremity provided ≥14 days have elapsed since completion of radiotherapy, provided the subject received ≤10 radiotherapy fractions and a dose ≤30 Gy to that site, and provided skull, spine, thorax or pelvis were not in the radiotherapy field.

• Subject has active systemic viral, bacterial or fungal infection(s) requiring treatment.

• Subject has 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.

• Subject has history of myocardial infarction or unstable angina ≤6 months prior to study treatment.

• Subject is known to be HIV positive or has active hepatitis infection.

• Subject is female who is pregnant or breastfeeding.