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Trial record 2 of 3 for:    tusc2

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04486833
Recruitment Status : Recruiting
First Posted : July 27, 2020
Last Update Posted : August 2, 2022
Sponsor:
Information provided by (Responsible Party):
Genprex, Inc.

Brief Summary:

The purpose of this randomized study is to determine the safety and efficacy of Reqorsa (quaratusugene ozeplasmid, formerly known as GPX-001) added to osimertinib in NSCLC patients with activating EGFR mutations who have progressed while on treatment with osimertinib. Reqorsa 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 will be conducted in 2 phases, a dose escalation and expansion phase (Phase 1) and a safety and efficacy evaluation phase (Phase 2). In Phase 1, patients will be enrolled in sequential cohorts treated with successively higher doses of Reqorsa in combination with osimertinib. When the recommended Phase 2 dose (RP2D) is determined, additional patients will be enrolled in an expansion cohort. In Phase 2, patient will be randomized to receive Reqorsa plus osimertinib or osimertinib alone.


Condition or disease Intervention/treatment Phase
Carcinoma, Non-Small Cell Lung Biological: quaratusugene ozeplasmid Drug: osimertinib Phase 1 Phase 2

Detailed Description:

Acclaim-1 is an open-label, multi-center, Phase 1/2 study evaluating Reqorsa (quaratusugene ozeplasmid) plus osimertinib versus monotherapy osimertinib 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 Reqorsa when given in combination with osimertinib will be identified. Once the RP2D is identified an expansion cohort will be enrolled to better characterize safety, tolerability, and preliminary anti-tumor activity.

Phase 2: Reqorsa 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 combination therapy or osimertinib alone in a 1 to 1 ratio and stratified based on prior local radiotherapy. Other subsets may be explored based on emergent data.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 92 participants
Allocation: Randomized
Intervention Model: Sequential Assignment
Intervention Model Description: Phase 1: 3+3 dose escalation to identify RP2D and expansion at RP2D. Phase 2: Parallel randomization to either Reqorsa at RP2D in combination or osimertinib alone.
Masking: Single (Outcomes Assessor)
Masking Description: Tumor responses will be assessed centrally using RECIST 1.1 by and independent radiology group blinded to treatment arm assignment.
Primary Purpose: Treatment
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
Actual Study Start Date : September 3, 2021
Estimated Primary Completion Date : December 2024
Estimated Study Completion Date : December 2025

Resource links provided by the National Library of Medicine

Drug Information available for: Osimertinib

Arm Intervention/treatment
Experimental: Phase 1

Up to 3 sequential dose escalation cohorts will be treated with Reqorsa intravenously on Day 1 in addition to osimertinib 80 mg fixed dose oral daily tablet during 21-day treatment cycles until disease progression or unacceptable toxicity.

The first group will receive Reqorsa IV infusion at 0.06 mg/kg, the next group 0.09 mg/kg and the third will receive 0.12 mg/kg. Additional Reqorsa dose levels may be evaluated until RP2D is identified. Once the RP2D is determined, an additional group of patients will be enrolled at the RP2D.

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:
  • GPX-001
  • 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 Name: Tagrisso

Experimental: Phase 2 Combination
Patients will receive the RP2D of Reqorsa intravenously on Day 1 in addition to osimertinib 80 mg fixed dose oral daily tablet during 21-day treatment cycles 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:
  • GPX-001
  • 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 Name: Tagrisso

Active Comparator: Phase 2 Active Comparator
Patients will continue on monotherapy osimertinib 80 mg fixed dose oral daily tablet until disease progression.
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 Name: Tagrisso




Primary Outcome Measures :
  1. Recommended Phase 2 Dose (RP2D) - Phase 1 [ Time Frame: First 21-days at each dose level ]

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

    The number of participants with dose-limiting toxicity (DLT) events utilizing 3+3 dose escalation design will be used to identify the MTD. Dose may be escalated or de-escalated based on the occurrence of DLTs to potentially identify the MTD. All events will be assessed by the Investigator for possible, probable or definite relation to either drug administered.


  2. Progression-free Survival (PFS2) - Phase 2 [ Time Frame: Approximately 9 months ]
    Number of months from randomization to the date of disease progression, confirmed by RESIST v1.1 or to the date of death due to any cause.


Secondary Outcome Measures :
  1. Overall Response Rate (ORR) - Phase 2 [ Time Frame: Approximately 9 months ]
    Number of patients with measurable lesions at baseline and confirmed objective complete response (CR) or partial response (PR) according to RECIST v1.1 after completing at least one 21-day cycle.

  2. Overall Survival (OS) - Phase 2 [ Time Frame: Approximately 21 months ]
    Number of months from randomization or date of first dose of study treatment to the date of death.

  3. Duration of Treatment [ Time Frame: 6 months ]
    Number of patients continuing combination therapy at 6 months (tolerability).

  4. Incidence of Adverse Events [ Time Frame: Approximately 10 months ]
    Number of treatment emergent adverse events graded according to the NCI-CTCAE version 5.0 criteria. From first dose of study treatment to 30 days after last dose.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically or cytologically documented non-small cell lung cancer (NSCLC).
  • Stage III or IV NSCLC or recurrent NSCLC that is not potentially curable by radiotherapy or surgery whether or not patient has received prior chemotherapy.
  • EGFR mutation-positive as detected by an FDA-approved test, based on results of most recent biopsy.
  • Achieved clinical response to osimertinib for ≥4 months.
  • Must have radiological progression on or after treatment with osimertinib and can have either asymptomatic disease or symptomatic disease. For Phase 2 only, eligibility for patients with symptomatic disease is restricted to those with limited metastasis (≤5 metastases).
  • Eastern Cooperative Oncology Arm (ECOG) performance score from 0 to 1.
  • 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.
  • If asymptomatic brain metastases are present must meet ALL criteria listed:

    • No history of seizures in the preceding 6 months.
    • Definitive treatment must be completed ≥21 days.
    • Patients must be off steroids administered because of brain metastases or related symptoms for ≥7 days.
    • Post-treatment imaging must demonstrate stability or regression of the brain metastases.
  • ANC >1500/mm3, platelet count >100,000/mm3 within ≤21 days.
  • Adequate renal function documented by serum creatinine of ≤1.5 mg/dL or calculated creatinine clearance >50 ml/min within ≤21 days.
  • Adequate hepatic function as documented by serum bilirubin <1.5 mg/dL and AST and ALT ≤2.5 X upper limit of normal (ULN) within ≤21 days.
  • Stable cardiac condition with a left ventricular ejection fraction ≥40% within ≤21 days.
  • If female of childbearing potential, must have negative serum pregnancy test (serum β-hCG) within ≤7 days.
  • Must agree to 2 forms of contraception including 1 highly effective and 1 effective methods during the study period and for 4 months following the last dose of study treatment.
  • If male, must agree to no sperm donation during study treatment and for an additional 4 months following the last dose of study treatment.
  • Must have voluntarily signed an informed consent in accordance with institutional policies.

Exclusion Criteria:

  • Unable to tolerate osimertinib treatment, leading to early treatment discontinuation or prolonged/frequent dosage modifications.
  • Received standard chemotherapy or monoclonal antibodies to treat NSCLC within ≤21 days.
  • Received prior gene therapy.
  • Other genetic characteristics (such as ALK, ROS, BRAF V600E mutations) which makes them a candidate for treatment with other approved targeted therapies.
  • Received radiotherapy to the skull, spine, thorax, or pelvis within ≤30 days.
  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04486833


Contacts
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Contact: Sr Director, Clinical Operations 1-877-774-GNPX kcombs@genprex.com
Contact: Chief Medical Officer 1-877-774-GNPX mberger@genprex.com

Locations
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United States, California
Valkyrie Clinical Trials Recruiting
Los Angeles, California, United States, 90067
Contact: Kristi Okino    562-833-1483    Kristi.okino@valkyrieclinicaltrials.com   
Principal Investigator: David Berz, MD         
United States, Colorado
Rocky Mountain Cancer Centers Recruiting
Lone Tree, Colorado, United States, 80124
Contact: Katherine Schleich    303-285-5018 ext 35018    Katherine.schleich@usoncology.com   
Contact: Joni Richman    303-336-2181    joni.richman@usoncology.com   
Principal Investigator: Robert M. Jotte, MD         
United States, Maryland
Maryland Oncology Hematology Recruiting
Rockville, Maryland, United States, 20850
Contact: Missy Almand    877-664-7724    missy.almand@usoncology.com   
Contact: Jake Brooks    877-664-7724    jake.brooks@usoncology.com   
Principal Investigator: John M. Wallmark, MD         
United States, Texas
Millennium Oncology Recruiting
Houston, Texas, United States, 77090
Contact: John Waldron    877-870-2640    jwaldron@wmrad.com   
Principal Investigator: Krishna K. Pachipala, MD         
United States, Virginia
Virginia Cancer Specialists Recruiting
Fairfax, Virginia, United States, 22031
Contact: Marcy Sullivan, RN, BSN    703-208-9268    marcy.sullivan@usoncology.com   
Contact: Monica Cochrane    703-208-3110    monica.cochrane@usoncology.com   
Principal Investigator: Alexander I. Spira, MD         
Sponsors and Collaborators
Genprex, Inc.
Investigators
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Study Director: Mark S. Berger, MD Genprex, Inc.
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Responsible Party: Genprex, Inc.
ClinicalTrials.gov Identifier: NCT04486833    
Other Study ID Numbers: ONC-003
First Posted: July 27, 2020    Key Record Dates
Last Update Posted: August 2, 2022
Last Verified: August 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Genprex, Inc.:
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:
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Carcinoma, Non-Small-Cell Lung
Carcinoma, Bronchogenic
Bronchial Neoplasms
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Osimertinib
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action