Quaratusugene Ozeplasmid (Reqorsa) and Osimertinib in Patients With Advanced Lung Cancer Who Progressed on Osimertinib (Acclaim-1)

January 20, 2026 updated by: Genprex, Inc.

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

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Acclaim-1 is an open-label, multi-center, Phase 1/2 study evaluating quaratusugene ozeplasmid (Reqorsa) plus osimertinib (investigational arm) versus platinum-based chemotherapy (control arm) in patients with advanced metastatic or recurrent NSCLC.

Toxicities will be assessed by the Investigator using United States National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 5.0. Serious Adverse Events and Dose Limiting Toxicities (DLT) will be reviewed by a Safety Review Committee.

Phase 1 - Dose Escalation: The RP2D of quaratusugene ozeplasmid when given in combination with osimertinib has been identified.

Phase 2a: This expansion cohort will be enrolled to better characterize safety, tolerability, and preliminary anti-tumor activity of the combination therapy.

Phase 2b: Quaratusugene ozeplasmid in combination with osimertinib will be further evaluated using the RP2D identified in Phase 1. Patients may receive local therapy, such as radiation therapy, to progressing lesions prior to enrollment. Patients will be randomized to receive either the investigational arm or the control arm in a 1 to 1 ratio and stratified based on prior local radiotherapy.

Study Type

Interventional

Enrollment (Estimated)

158

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Sr Director, Clinical Operations
  • Phone Number: 1-877-774-GNPX
  • Email: kcombs@genprex.com

Study Contact Backup

Study Locations

  • United States
    • California
      • Los Angeles, California, United States, 90067
    • Colorado
      • Lone Tree, Colorado, United States, 80124
    • Illinois
      • Urbana, Illinois, United States, 61801
        • Recruiting
        • Carle Cancer Institute
        • Principal Investigator:
          • Kendrith Rowland, MD
        • Contact:
    • Kentucky
      • Lexington, Kentucky, United States, 40536
        • Recruiting
        • Markey Cancer Center
        • Principal Investigator:
          • Zhonglin Hao, MD
        • Contact:
    • Maryland
      • Rockville, Maryland, United States, 20850
    • New Jersey
      • Paramus, New Jersey, United States, 07652
        • Recruiting
        • The Valley Hospital - Luckow Pavilion
        • Contact:
        • Principal Investigator:
          • Eli D. Kirshner, MD
    • Ohio
    • Texas
      • Houston, Texas, United States, 77090
        • Terminated
        • Millennium Oncology
    • Virginia
      • Fairfax, Virginia, United States, 22031
        • Recruiting
        • Virginia Cancer Specialists
        • Principal Investigator:
          • Alexander I. Spira, MD
        • Contact:
      • Norfolk, Virginia, United States, 23502
        • Recruiting
        • Virginia Oncology Associates
        • Contact:
        • Principal Investigator:
          • Boon Kok, MD

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.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Investigational
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
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.
Other Names:
  • Reqorsa
Drug: osimertinib
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.
Other Names:
  • Tagrisso
Active Comparator: Control
In the control arm of Phase 2b, patients will receive platinum-based chemotherapy until disease progression or unacceptable toxicity.
Drug: Platinum-Based Chemotherapy
Cisplatin and carboplatin are intravenously administered platinum agents that are combined with other cytotoxic chemotherapy agents such as pemetrexed.
Other Names:
  • cisplatin
  • carboplatin

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Recommended Phase 2 Dose (RP2D) - Phase 1
Time Frame: First 21-day treatment cycle for each dose level cohort
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
Time Frame: Approximately 3 months
ORR (complete response [CR]+ partial response [PR]) according to RECIST using best overall response.
Approximately 3 months
Progression-free Survival (PFS) - Phase 2b
Time Frame: Approximately 11 months
PFS from randomization to disease progression or death. Response according to RECIST.
Approximately 11 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Pharmacokinetics (PK) of Quaratusugene Ozeplasmid - Phase 1
Time Frame: First 21-day treatment cycle
Concentration of quaratusugene ozeplasmid in whole blood samples.
First 21-day treatment cycle
Overall Survival (OS) - Phase 2a
Time Frame: Approximately 21 months
OS from first dose until death or discontinuation due to withdrawal of consent.
Approximately 21 months
Overall Survival (OS) - Phase 2b
Time Frame: Approximately 21 months
OS from randomization to death or discontinuation due to withdrawal of consent.
Approximately 21 months
Progression-free Survival (PFS) - Phase 1
Time Frame: Approximately 9 months
PFS from first dose to disease progression or death. Response according to RECIST.
Approximately 9 months
Overall Response Rate (ORR) - Phase 1
Time Frame: Approximately 3 months
ORR (CR+ PR) according to RECIST using best overall response.
Approximately 3 months
Duration of Response (DOR) - Phase 1
Time Frame: Approximately 9 months
DOR (CR + PR) from response to disease progression. Response according to RECIST.
Approximately 9 months
Progression-free Survival (PFS) - Phase 2a
Time Frame: Approximately 11 months
PFS from first dose to disease progression or death. Response according to RECIST.
Approximately 11 months
Time to Progression (TTP) - Phase 2a
Time Frame: Approximately 11 months
TTP from first dose to disease progression. Response according to RECIST.
Approximately 11 months
Pharmacokinetics (PK) of Quaratusugene Ozeplasmid - Phase 2a
Time Frame: Approximately 22 days
Concentration of quaratusugene ozeplasmid in whole blood samples.
Approximately 22 days
Overall Response Rate (ORR) - Phase 2b
Time Frame: Approximately 3 months
ORR (CR+ PR) according to RECIST using best overall response.
Approximately 3 months
Time to Progression (TTP) - Phase 2b
Time Frame: Approximately 11 months
TTP from first dose to disease progression. Response according to RECIST.
Approximately 11 months
Duration of Response (DOR) - Phase 2b
Time Frame: Approximately 11 months
DOR (CR + PR) according to RECIST from response to disease progression.
Approximately 11 months
Incidence of Adverse Events - Phase 2b
Time Frame: Approximately 11 months
Treatment-related adverse events (AEs) graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events.
Approximately 11 months
Pharmacokinetics (PK) of Quaratusugene Ozeplasmid - Phase 2b
Time Frame: Approximately 22 days
Concentration of quaratusugene ozeplasmid in whole blood samples.
Approximately 22 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Genprex, Inc.

Investigators

  • Study Director: Mark S. Berger, MD, Genprex, Inc.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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 Major Dates

Study Start (Actual)

September 3, 2021

Primary Completion (Estimated)

March 1, 2028

Study Completion (Estimated)

March 1, 2029

Study Registration Dates

First Submitted

July 22, 2020

First Submitted That Met QC Criteria

July 22, 2020

First Posted (Actual)

July 27, 2020

Study Record Updates

Last Update Posted (Actual)

January 21, 2026

Last Update Submitted That Met QC Criteria

January 20, 2026

Last Verified

January 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ONC-003

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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