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

NCT04486833 | Recruiting Phase 1 FDA Drug

• 1 other identifier: ONC-003
• Study Type: interventional
• Target: 158
• Locations: 1 country
• Sites: 10

Brief Summary

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.

Conditions

Carcinoma, Non-Small Cell Lung

Keywords

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

Outcome Measures

Primary Outcomes (3)

• Recommended Phase 2 Dose (RP2D) - Phase 1

  RP2D, which will be the maximum tolerated dose (MTD) or, if the MTD is not defined by the safety data, RP2D will be determined based on an integrated assessment of all available clinical safety and preliminary efficacy data.

  First 21-day treatment cycle for each dose level cohort

• Overall Response Rate (ORR) - Phase 2a

  ORR (complete response \[CR\]+ partial response \[PR\]) according to RECIST using best overall response.

  Approximately 3 months

• Progression-free Survival (PFS) - Phase 2b

  PFS from randomization to disease progression or death. Response according to RECIST.

  Approximately 11 months

Secondary Outcomes (14)

• Progression-free Survival (PFS) - Phase 1

  Approximately 9 months

• Overall Response Rate (ORR) - Phase 1

  Approximately 3 months

• Duration of Response (DOR) - Phase 1

  Approximately 9 months

• Pharmacokinetics (PK) of Quaratusugene Ozeplasmid - Phase 1

  First 21-day treatment cycle

• Progression-free Survival (PFS) - Phase 2a

  Approximately 11 months

Study Arms (2)

Investigational

EXPERIMENTAL

In Phase 1, Phase 2a and the investigational arm of Phase 2b, patients will receive their assigned dose of quaratusugene ozeplasmid (intravenous administration once every 21 days) plus osimertinib (80 mg fixed dose oral tablet taken daily starting on Day 1 through Day 21 of every 21-day treatment cycle) until disease progression or unacceptable toxicity.

Biological: quaratusugene ozeplasmid; Drug: osimertinib

Control

ACTIVE COMPARATOR

In the control arm of Phase 2b, patients will receive platinum-based chemotherapy until disease progression or unacceptable toxicity.

Drug: Platinum-Based Chemotherapy

Interventions

osimertinib DRUG

Osimertinib is a 3rd generation EGFR tyrosine kinase inhibitor (TKI) oral tablet administered daily, as indicated for treatment of patients with metastatic NSCLC whose tumors have EGFR genetic deletions or mutations.

Also known as: Tagrisso

Investigational

Platinum-Based Chemotherapy DRUG

Cisplatin and carboplatin are intravenously administered platinum agents that are combined with other cytotoxic chemotherapy agents such as pemetrexed.

Also known as: cisplatin, carboplatin

Control

quaratusugene ozeplasmid BIOLOGICAL

Quaratusugene ozeplasmid is an experimental non-viral immunogene therapy utilizing the TUSC2 gene, designed to target cancer cells by interrupting cell signaling pathways that allow cancer cells to grow, reestablishing pathways that promote cancer cell death and modulating the immune response against cancer cells.

Also known as: Reqorsa

Investigational

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥18 years.
• Histologically or cytologically documented NSCLC.
• Stage III or IV NSCLC or recurrent NSCLC that is not potentially curable by radiotherapy or surgery.
• 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.
• 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.
• Must have radiological progression on osimertinib treatment and can have either asymptomatic disease or symptomatic disease. In addition:
• Must have measurable disease per RECIST 1.1.
• 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.
• Eastern Cooperative Oncology Group performance status (ECOG PS) score from 0 to 1.
• 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.
• Asymptomatic brain metastases must meet ALL criteria of the following (a-d):
• No history of seizures in the preceding six months.

You may not qualify if:

• Unable to tolerate osimertinib treatment, leading to early treatment discontinuation or prolonged/frequent dosage modifications as determined by the Investigator.
• Received prior gene therapy.
• Other genetic characteristics (such as ALK, ROS, BRAF V600E mutations) which make them a candidate for treatment with other approved targeted therapies.
• Received radiotherapy to the skull, spine, thorax, or pelvis within ≤30 days.
• Active concurrent malignancies, i.e., cancers other than NSCLC that require systemic therapy.
• Active systemic viral, bacterial, or fungal infection(s) requiring treatment.
• 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.
• History of myocardial infarction or unstable angina within ≤6 months.
• Known human immunodeficiency virus (HIV) infection or has active hepatitis infection.
• Female who is pregnant or breastfeeding.

Sponsors & Collaborators

• Genprex, Inc.: lead

Study Sites (10)

Valkyrie Clinical Trials

Los Angeles, California, 90067, United States

RECRUITING

Rocky Mountain Cancer Centers

Lone Tree, Colorado, 80124, United States

RECRUITING

Carle Cancer Institute

Urbana, Illinois, 61801, United States

RECRUITING

Markey Cancer Center

Lexington, Kentucky, 40536, United States

RECRUITING

Maryland Oncology Hematology

Rockville, Maryland, 20850, United States

RECRUITING

The Valley Hospital - Luckow Pavilion

Paramus, New Jersey, 07652, United States

RECRUITING

Gabrail Cancer Center Research

Canton, Ohio, 44718, United States

RECRUITING

Millennium Oncology

Houston, Texas, 77090, United States

TERMINATED

Virginia Cancer Specialists

Fairfax, Virginia, 22031, United States

RECRUITING

Virginia Oncology Associates

Norfolk, Virginia, 23502, United States

RECRUITING

Related Publications (1)

• Spira AI, Berz D, Jotte RM, Pachipala KK, Berger MS. Dose Escalation Trial of the Combination of Osimertinib and Quaratusugene Ozeplasmid Gene Therapy in Patients with Advanced NSCLC. Clin Lung Cancer. 2026 Jan;27(1):75-81. doi: 10.1016/j.cllc.2025.11.009. Epub 2025 Nov 17.

  PMID: 41385873 BACKGROUND

Related Links

• Dose Escalation Trial of the Combination of Osimertinib and Quaratusugene Ozeplasmid Gene Therapy in Patients with Advanced NSCLC

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

osimertinib; Platinum Compounds; Cisplatin; Carboplatin

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Inorganic Chemicals; Chlorine Compounds; Nitrogen Compounds; Coordination Complexes; Organic Chemicals

Study Officials

• Mark S. Berger, MD

  Genprex, Inc.

  STUDY DIRECTOR

Central Study Contacts

Sr Director, Clinical Operations

CONTACT

1-877-774-GNPX; kcombs@genprex.com

Chief Medical Officer

CONTACT

1-877-774-GNPX; mberger@genprex.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Phase 1: 3+3 dose escalation to identify RP2D. Phase 2: RP2D further evaluated in Phase 2a expansion followed by parallel randomization in a 1:1 ratio to either investigational arm or control arm.

Study Record Dates

• First Submitted: July 22, 2020
• First Posted: July 27, 2020
• Study Start: September 3, 2021
• Primary Completion (Estimated): March 1, 2028
• Study Completion (Estimated): March 1, 2029
• Last Updated: January 21, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (10)