RECRUITING

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

Conditions

Carcinoma, Non-Small Cell Lung Epidermal growth factor receptor mutation (EGFR)osimertinib Tumor suppressor gene 2 (TUSC2)Lipid nanoparticle (LNP)Gene therapy Tagrisso FUS1-nanoparticles NSCLC Reqorsa quaratusugene ozeplasmid

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

The purpose of this randomized study is to determine the safety and efficacy of quaratusugene ozeplasmid (Reqorsa) added to osimertinib in NSCLC patients with activating EGFR mutations who have progressed while on treatment with osimertinib. Quaratusugene ozeplasmid consists of non-viral lipid nanoparticles that encapsulate a DNA plasmid with the TUSC2 tumor suppressor gene and is the first systemic gene therapy for cancer. The study is comprised of a Phase 1 dose escalation portion and two Phase 2 portions evaluating safety and efficacy. Enrollment in the Phase 1 dose escalation portion is complete and the recommended Phase 2 dose (RP2D) was determined. Phase 2a has initiated and enrolled patients are treated with quaratusugene ozeplasmid at the RP2D in combination with osimertinib. In Phase 2b, patients will be randomized to receive either quaratusugene ozeplasmid plus osimertinib or platinum-based chemotherapy.

Official Title

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

Quick Facts

Study Start:2021-09-03

Study Completion:2029-03

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT04486833

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion 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. * 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.	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.

Inclusion Criteria

Exclusion 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.
* 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.

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.

Contacts and Locations

Study Contact

Sr Director, Clinical Operations

CONTACT

1-877-774-GNPX

kcombs@genprex.com

Chief Medical Officer

CONTACT

1-877-774-GNPX

mberger@genprex.com

Principal Investigator

Mark S. Berger, MD

STUDY_DIRECTOR

Genprex, Inc.

Study Locations (Sites)

Valkyrie Clinical Trials

Los Angeles, California, 90067

United States

Rocky Mountain Cancer Centers

Lone Tree, Colorado, 80124

United States

Carle Cancer Institute

Urbana, Illinois, 61801

United States

Maryland Oncology Hematology

Rockville, Maryland, 20850

United States

The Valley Hospital - Luckow Pavilion

Paramus, New Jersey, 07652

United States

Millennium Oncology

Houston, Texas, 77090

United States

Virginia Cancer Specialists

Fairfax, Virginia, 22031

United States

Collaborators and Investigators

Sponsor: Genprex, Inc.

Mark S. Berger, MD, STUDY_DIRECTOR, Genprex, Inc.

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2021-09-03

Study Completion Date2029-03

Study Record Updates

Study Start Date2021-09-03

Study Completion Date2029-03

Terms related to this study

Keywords Provided by Researchers

Epidermal growth factor receptor mutation (EGFR)
osimertinib
Tumor suppressor gene 2 (TUSC2)
Lipid nanoparticle (LNP)
Gene therapy
Tagrisso
FUS1-nanoparticles
NSCLC
Reqorsa
quaratusugene ozeplasmid

Additional Relevant MeSH Terms

Carcinoma, Non-Small Cell Lung