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Trial record 2 of 2 for:    tusc2

TUSC2-nanoparticles (GPX-001) and Osimertinib in Patients With Stage IV Lung Cancer Who Progressed on Osimertinib Alone

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ClinicalTrials.gov Identifier: NCT04486833
Recruitment Status : Not yet recruiting
First Posted : July 27, 2020
Last Update Posted : August 7, 2020
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 TUSC2, tumor suppressor gene, encapsulate by non-viral lipid nanoparticles) added to osimertinib in NSCLC patients with activating EGFR mutations who have progressed while on treatment with osimertinib.

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 GPX-001 in combination with osimertinib. In Phase 2, patient will be randomized to receive GPX-001 plus osimertinib or osimertinib alone.


Condition or disease Intervention/treatment Phase
Carcinoma, Non-Small-Cell Lung Biological: Quaratusugene ozeplasmid - intravenous infusion Drug: Osimertinib Oral Tablet Phase 1 Phase 2

Detailed Description:

GEN-104 is an open-label, multi-center, Phase 1/2 study evaluating quaratusugene ozeplasmid (GPX-001) plus osimertinib versus monotherapy osimertinib in patients with advanced metastatic or recurrent Non-small Cell Lung Cancer.

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 an independent Data Safety Monitoring Board.

Phase 1 - Dose Escalation: The prospective maximum tolerated dose (MTD) in combination with osimertinib, identified in the Dose Escalation phase will be confirmed in at least 6 patients to obtain additional safety and anti-tumor activity data. This confirmed GPX-001 dose will be the recommended phase 2 dose (RP2D) used in Phase 2.

Phase 2: In the this Phase, GPX-001 in combination with osimertinib will be further evaluated using the RP2D identified in Phase 1. 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 : 100 participants
Allocation: Randomized
Intervention Model: Sequential Assignment
Intervention Model Description: Phase 1: 3+3 dose escalation to identify RP2D. Phase 2: parallel randomization to either GPX-001 at RP2D in combination or osimertinib alone.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1/2 Open-Label, Dose-escalation and Clinical Response Study of GPX-001 in Combination With Osimertinib in Patients With Advanced, Metastatic EGFR-mutant Non-small Cell Lung Cancer
Estimated Study Start Date : June 2021
Estimated Primary Completion Date : September 2024
Estimated Study Completion Date : March 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 GPX-001 intravenously on Day 1 in addition to osimertinib 80 mg fixed dose oral daily tablet.

The first group will receive GPX-001 IV infusion at 0.06 mg/kg, the next group 0.09 mg/kg and the third will receive 0.12 mg/kg. Additional GPX-001 dose levels may be evaluated until RP2D is identified.

Biological: Quaratusugene ozeplasmid - intravenous infusion
Quaratusugene ozeplasmid is an experimental nonviral immunogene 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 response against cancer cells.
Other Names:
  • GPX-001
  • DOTAP: Chol-TUSC2 Liposomal Complex

Drug: Osimertinib Oral Tablet
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 GPX-001 intravenously on Day 1 in addition to osimertinib 80 mg fixed dose oral daily tablet starting on Day 10. The 21-day treatment cycle will continue until second progression event (PFS2) or unacceptable toxicity.
Biological: Quaratusugene ozeplasmid - intravenous infusion
Quaratusugene ozeplasmid is an experimental nonviral immunogene 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 response against cancer cells.
Other Names:
  • GPX-001
  • DOTAP: Chol-TUSC2 Liposomal Complex

Drug: Osimertinib Oral Tablet
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 second progression event (PFS2).
Drug: Osimertinib Oral Tablet
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. Maximum Tolerated Dose (MTD) - Phase 1 [ Time Frame: First 21-days at each dose level ]
    Number of participants with dose-limiting toxicity (DLT) events utilizing 3+3 dose escalation design. Dose may be escalated or de-escalated based on the occurrence of DLTs to 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 24 months ]
    Number of months from randomization (after first progression on osimertinib) to the date of second disease progression event, confirmed by RESIST v1.1 or to the date of death due to any causes.


Secondary Outcome Measures :
  1. Overall Response Rate (ORR) for Phase 2 dose [ Time Frame: Approximately 12 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 and then every 3 months thereafter up to 12 cycles of the combination therapy.

  2. Overall Survival (OS) for Phase 2 dose [ Time Frame: Approximately 24 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 12 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

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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 4 NSCLC or recurrent NSCLC that is not potentially curable by radiotherapy or surgery whether or not they have received prior chemotherapy
  • EGFR mutation-positive as detected by an FDA-approved test
  • Must have progressed on or after treatment with osimertinib prior to study entry
  • Eastern Cooperative Oncology Arm performance score from 0 to 1
  • Subjects must be ≥4 weeks beyond major surgical procedures such as thoracotomy, laparotomy or joint replacement, and must be ≥1.5 weeks 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. Note: placement of catheter is not considered minor surgery for this study.
  • Subjects with asymptomatic brain metastases that have been treated are eligible if the following criteria are met:

    • No history of seizures in the preceding 6 months.
    • Definitive treatment must have been completed ≥4 weeks prior to start of study treatment.
    • Subjects must be off steroids that were being administered because of brain metastases or related symptoms for ≥2 weeks prior to start of study treatment.
    • Post-treatment imaging ≤2 weeks of study treatment must demonstrate stability or regression of the brain metastases.
  • ANC >1500/mm3, platelet count >100,000/mm3 ≤14 days of study treatment
  • PT and PTT <1.25 times the upper limit of normal ≤14 days of study treatment
  • Adequate renal function documented by serum creatinine of ≤1.5 mg/dl or calculated creatinine clearance >50 ml/min ≤14 days of study treatment
  • Adequate hepatic function as documented by serum bilirubin <1.5 mg/dl and liver transaminases ≤2.5 X upper limit of normal ≤14 days of study treatment
  • Stable cardiac condition with a left ventricular ejection fraction ≥40% within 28 days of study treatment
  • If female and of childbearing potential, must have negative serum pregnancy test ≤7 days of study treatment (Note: non-childbearing is defined as greater than one year post- menopausal or surgically sterilized).
  • Must agree to practice effective birth control (e.g., abstinence, intrauterine device for female subjects) during the study period.
  • Must have voluntarily signed an informed consent in accordance with institutional policies.

Exclusion Criteria:

  • Subject who did not tolerate osimertinib treatment, leading to early treatment discontinuation or prolonged/ frequent dosage modifications.
  • Subject received standard chemotherapy with FDA-approved agents ≤21 days prior to study treatment.
  • Subject received prior gene therapy.
  • Subjects with other genetic characteristics which make them candidates for treatment with other approved targeted therapies, or prior treatment with checkpoint inhibitors
  • Subject received investigational therapy (i.e., agents that are not FDA approved), including monoclonal antibodies such as bevacizumab or cetuximab, or has received radiotherapy to the skull, spine, thorax or pelvis within ≤30 days of start of study treatment. Subjects are permitted to have received palliative radiotherapy to an extremity provided ≥14 days have elapsed since completion of radiotherapy, provided the subject received ≤10 radiotherapy fractions and a dose ≤30 Gy to that site, and provided skull, spine, thorax or pelvis were not in the radiotherapy field.
  • Subject has active systemic viral, bacterial or fungal infection(s) requiring treatment.
  • Subject has 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.
  • Subject has history of myocardial infarction or unstable angina ≤6 months prior to study treatment.
  • Subject is known to be HIV positive or has active hepatitis infection.
  • Subject is 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: VP of Clinical Operations 1-877-774-GNPX sinman@genprex.com

Sponsors and Collaborators
Genprex, Inc.
Investigators
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Study Director: Michael Redman Executive VP and COO
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Responsible Party: Genprex, Inc.
ClinicalTrials.gov Identifier: NCT04486833    
Other Study ID Numbers: GEN-104
First Posted: July 27, 2020    Key Record Dates
Last Update Posted: August 7, 2020
Last Verified: August 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Coded IPD will be provided to participating investigators.
Supporting Materials: Clinical Study Report (CSR)
Time Frame: At the end of the study
Access Criteria: All data request should be made directly to Genprex (Study Sponsor) for access determination.

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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
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