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Trial record 1 of 2 for:    REQORSA
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TUSC2-nanoparticles (GXP-001) in Combination With Pembrolizumab in Previously Treated Non-small Lung Cancer (Acclaim-2)

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ClinicalTrials.gov Identifier: NCT05062980
Recruitment Status : Not yet recruiting
First Posted : September 30, 2021
Last Update Posted : September 30, 2021
Sponsor:
Information provided by (Responsible Party):
Genprex, Inc.

Brief 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, encapsulated by non-viral lipid nanoparticles) in combination with pembrolizumab in patients with previously treated NSCLC.

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 GXP-001 in combination with pembrolizumab.

In Phase 2, patients will be randomized to receive GXP-001 with pembrolizumab or docetaxel +/- ramucirumab (active comparator).


Condition or disease Intervention/treatment Phase
Non Small Cell Lung Cancer Biological: quaratusugene ozeplasmid Drug: Pembrolizumab Injection [Keytruda] Drug: Docetaxel injection Drug: Ramucirumab Injection [Cyramza] Phase 1 Phase 2

Detailed Description:

ONC-004 is a multi-center, open-label 2-arm study of GPX-001 in combination with pembrolizumab versus docetaxel +/- ramucirumab (active comparator) in previously treated NSCLC with any PD-L1 TPS and NOT considered refractory to pembrolizumab, as defined by having achieved at least a 3-month clinical benefit to previous pembrolizumab-containing treatment.

The total duration of study for each patient will be dependent upon the safety, tolerability, and efficacy of the combination regimen of GPX-001 and pembrolizumab.

The Phase 1 portion of the study will involve a 3+3 dose escalation schema of GPX-001 up to 0.12 mg/kg in combination with a fixed dose of pembrolizumab (200 mg) administered once via intravenous (IV) infusion during each 21-day treatment cycle. Three GPX-001 doses will be tested (0.06, 0.09 and 0.12 mg/kg administered on Day 1 of a 21-day treatment cycle).

The Phase 2 portion of the study is a randomized, open-label 2-arm study of GPX-001 in combination with pembrolizumab versus docetaxel ± ramucirumab. In Phase 2, 126 patients will be randomized 2:1 to the combination versus active comparator treatment arms, respectively. The 84 patients randomized to the combination arm will receive GPX-001, at the RP2D identified in Phase 1, in combination with 200 mg pembrolizumab either during each 21-day cycle until disease progression or unacceptable toxicity as determined by the investigator. The 42 patients randomized to the active comparator arm will receive docetaxel at the FDA-approved dose of 75 mg/m2 every 21 days until disease progression or unacceptable toxicity as determined by the investigator. Investigators are permitted to administer docetaxel in combination with ramucirumab at their discretion.

All patients will be assessed radiologically for tumor response until disease progression according to RECIST 1.1 criteria approximately every 6-8 weeks.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 156 participants
Allocation: Randomized
Intervention Model: Sequential Assignment
Intervention Model Description: Phase 1: 3+3 dose escalation to identify RP2D followed by a 12 patient dose expansion cohort. Phase 2: Parallel randomization in a 2:1 ratio to either GXP-001 at RP2D in combination with pembrolizumab or docetaxel +/- ramucirumab.
Masking: Single (Outcomes Assessor)
Masking Description: Tumor responses will be assessed centrally using RECIST 1.1 criteria by an 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 Pembrolizumab Versus Docetaxel With or Without Ramucirumab in Patients With Previously Treated Non-Small Cell Lung Cancer
Estimated Study Start Date : December 2021
Estimated Primary Completion Date : December 2023
Estimated Study Completion Date : December 2025

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lung Cancer

Arm Intervention/treatment
Experimental: Phase 1

Up to 3 sequential dose escalation cohorts will be treated with GPX-001 intravenously on Day 1 in addition to pembrolizumab 200 mg fixed dose infusion every 21-days until progression or unacceptable toxicity.

The first group will receive GPX-001 IV infusion at 0.06 mg/kg, the next group 0.09 mg/kg and the third group will receive 0.12 mg/kg. An expansion cohort of 12 patients will receive the MTD to confirm RP2D for Phase 2 portion.

Biological: quaratusugene ozeplasmid
Quaratusugene ozeplasmid is an experimental nonviral immunoogene therapy utilizing the TUSC2 gene, designed to target cancer cells by interrupting cell signaling pathways that allow cancer cells to grow, re-establishing pathways that promote cancer cell death and modulating the immune system response against cancer cells.
Other Names:
  • GPX-001
  • REQORSA

Drug: Pembrolizumab Injection [Keytruda]
pembrolizumab is a programmed death receptor-1 (PD-1) blocking antibody indicated for treatment of patients with metastatic NSCLC.

Experimental: Phase 2 Combination
Patients will receive the RP2D of GXP-001 intravenously on Day 1 in addition to pembrolizumab 200 mg fixed dose infusion every 21-days until progression or unacceptable toxicity.
Biological: quaratusugene ozeplasmid
Quaratusugene ozeplasmid is an experimental nonviral immunoogene therapy utilizing the TUSC2 gene, designed to target cancer cells by interrupting cell signaling pathways that allow cancer cells to grow, re-establishing pathways that promote cancer cell death and modulating the immune system response against cancer cells.
Other Names:
  • GPX-001
  • REQORSA

Drug: Pembrolizumab Injection [Keytruda]
pembrolizumab is a programmed death receptor-1 (PD-1) blocking antibody indicated for treatment of patients with metastatic NSCLC.

Active Comparator: Phase 2 Active Comparator
Patients will receive docetaxel 75 mg/m2 infusion with or without ramucirumab 10 mg/kg infusion every 21 days until progression or unacceptable toxicity.
Drug: Docetaxel injection
docetaxel is a microtubule inhibitor indicated for locally advanced or metastatic NSCLC after platinum-based chemotherapy failure.

Drug: Ramucirumab Injection [Cyramza]
ramucirumab is a human vascular endothelial growth factor receptor 2 (VEGFR2) antagonist indicated for in combination with docetaxel for treatment of NSCLC with disease progression after platinum-based chemotherapy.




Primary Outcome Measures :
  1. Maximum Tolerated Dose (MTD) - Phase 1 [ Time Frame: up to 3 weeks ]
    Dose limiting toxicity (DLT), defined as any ≥ Grade 3 prolonged non-hematological toxicity or ≥ Grade 4 prolonged hematological, organ or non-hematological toxicity or any Grade 3 prolonged cytokine release syndrome (CRS) or any Grade 4 CRS occurring during the first cycle of therapy and considered to be possibly, probably, or definitely related to GPX-001.

  2. Progression-free Survival (PFS) - Phase 2 [ Time Frame: 24 months ]
    Number of months from randomization to the date of disease progression, confirmed by RECIST v1.1 criteria or to the date of death due to any cause.



Information from the National Library of Medicine

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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:

  1. Adults ≥ 18 years of age.
  2. Voluntarily signed an informed consent in accordance with institutional policies.
  3. Histologically or cytologically documented NSCLC with locally advanced or metastatic stage IV disease. Note: Any level of PD-L1 TPS is allowed.
  4. Achieved clinical benefit to prior pembrolizumab/platinum-based chemotherapy for at least 3 months and subsequently progressed with radiological tumor assessment performed within 28 days of enrollment.
  5. Eastern Cooperative Oncology Arm (ECOG) performance score from 0 to 1.
  6. 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.
  7. Demonstrate adequate organ function, as determined by the following laboratory values obtained within 7 days prior to enrollment:

    1. Absolute neutrophil count (ANC) ≥ 1,500/μL,
    2. Platelets ≥ 100,000/μL,
    3. Hemoglobin ≥ 9.0 g/dL ≥ 4 weeks without transfusions,
    4. International Normalized Ratio (INR) or Prothrombin Time (PT): ≤ 1.5 × upper limit of normal (ULN) unless the patient is receiving anticoagulant therapy as long as PT is within therapeutic range of intended use of anticoagulants,
    5. Activated Partial Thromboplastin Time (aPTT) or Partial Thromboplastin Time (PTT): ≤ 1.5 × ULN unless the patient is receiving anticoagulant therapy as long as aPTT is within therapeutic range of intended use of anticoagulants,
    6. Creatinine ≤ 1.5 × ULN OR Calculated creatinine clearance (CrCl) ≥ 60 mL/min for patients with creatinine levels > 1.5 × ULN,
    7. Serum total bilirubin ≤ 1.0 × ULN,
    8. AST and ALT ≤ 1.5 × ULN,
    9. Alkaline phosphatase ≤ 2.5 x ULN.
  8. Stable cardiac condition with a left ventricular ejection fraction > 40%.
  9. If treated, asymptomatic brain metastases are present, must meet ALL criteria listed (a-d):

    1. No history of seizures in the preceding 6 months,
    2. Definitive treatment must be completed ≥ 4 weeks prior to enrollment,
    3. Stopped steroid treatments administered because of brain metastases or related symptoms for ≥ 2 weeks prior to enrollment,
    4. Post-treatment imaging must demonstrate stability or regression of the brain metastases.
  10. Female patients must have a negative serum pregnancy test at screening (within 7 days of enrollment) if of childbearing potential or be of non-childbearing potential.
  11. Female patients of childbearing potential 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 4 months following the last dose of study treatment.
  12. Male patients must agree to no sperm donation during study treatment and for an additional 4 months following the last dose of study treatment.

Exclusion Criteria:

  1. Unable to tolerate pembrolizumab treatment, leading to early treatment discontinuation or prolonged/ frequent dosage modifications.
  2. Hypersensitivity to docetaxel or polysorbate 80 (Phase 2 only)
  3. Patients at risk of tumor lysis syndrome [e.g., renal impairment, hyperuricemia, bulky tumor (Phase 2 only)]
  4. Received prior systemic chemotherapy or monoclonal antibodies for the treatment of the participant's advanced or metastatic disease within 1 month of study enrollment
  5. Received prior gene therapy.
  6. Received any radiotherapy to the skull, spine, thorax or pelvis within 1 month of study enrollment.
  7. Expected to require any other form of antineoplastic therapy while participating in the study.
  8. Received a live-virus vaccination within 1 month of planned treatment start. Seasonal flu vaccines that do not contain live virus are permitted.
  9. Has known active CNS metastases and/or carcinomatous meningitis.
  10. Active, known, or suspected autoimmune disease.
  11. Active systemic viral, bacterial, or fungal infections(s) requiring treatment.
  12. Serious concurrent illness or psychological, familial, sociological, geographical, or other condition that, in the opinion of the investigator, would prevent adequate follow-up and compliance with the study protocol.
  13. A condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study enrollment. Inhaled or topical steroids and adrenal replacement doses ≤10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
  14. Active concurrent malignancies, i.e., cancers other than NSCLC.
  15. Has a second, concurrent, untreated malignancy.
  16. History of symptomatic interstitial lung disease or pneumonitis that required oral or IV glucocorticoids to assist with management.
  17. History of myocardial infarction or unstable angina within the past 6 months.
  18. Presence of pre-existing peripheral neuropathy that is ≥ Grade 2 by National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 (NCI-CTCAE) criteria.
  19. Is, at the time of signing informed consent, a regular user (including "recreational use") of any illicit drugs or has a recent history (within the last year) of substance abuse (including alcohol) requiring medical intervention.
  20. Known human immunodeficiency virus (HIV) infection or has active hepatitis infection.
  21. Female patients who are 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): NCT05062980


Contacts
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Contact: Shannon Inman 1-877-774-GNPX sinman@genprex.com

Sponsors and Collaborators
Genprex, Inc.
Investigators
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Principal Investigator: Daniel Morgensztern, MD Washington University School of Medicine
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Responsible Party: Genprex, Inc.
ClinicalTrials.gov Identifier: NCT05062980    
Other Study ID Numbers: ONC-004
First Posted: September 30, 2021    Key Record Dates
Last Update Posted: September 30, 2021
Last Verified: September 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Genprex, Inc.:
Tumor suppressor gene 2 (TUSC2)
Lipid nanoparticle (LNP)
pembrolizumab
KEYTRUDA
Gene therapy
NSCLC
docetaxel
REQORSA
Acclaim-2
Additional relevant MeSH terms:
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Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Docetaxel
Pembrolizumab
Ramucirumab
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Immunological