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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05062980




Registration number
NCT05062980
Ethics application status
Date submitted
20/09/2021
Date registered
30/09/2021
Date last updated
1/10/2024

Titles & IDs
Public title
Quaratusugene Ozeplasmid (Reqorsa) in Combination with Pembrolizumab in Previously Treated Non-Small Lung Cancer
Scientific 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
Secondary ID [1] 0 0
ONC-004
Universal Trial Number (UTN)
Trial acronym
Acclaim-2
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Non Small Cell Lung Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lung - Mesothelioma
Cancer 0 0 0 0
Lung - Non small cell
Cancer 0 0 0 0
Lung - Small cell

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Other - quaratusugene ozeplasmid
Treatment: Drugs - pembrolizumab
Treatment: Drugs - docetaxel
Treatment: Drugs - ramucirumab
Treatment: Drugs - Investigator's Treatment of Choice

Experimental: Investigational - In Phase 1, the dose expansion portion of Phase 2 and the investigational arm of the randomized portion of Phase 2, patients will receive their assigned dose of quaratusugene ozeplasmid (via intravenous infusion) in combination with a fixed 200 mg dose of pembrolizumab (via intravenous infusion) once in every 21-day treatment cycle until disease progression or unacceptable toxicity.

Active comparator: Control - In the control arm of the randomized portion of Phase 2, patients will receive either 75 mg/m2 docetaxel (via intravenous infusion) with or without 10 mg/kg ramucirumab (via intravenous infusion) -OR- investigator's choice of treatment. The treatment regimen for patients randomized to the control arm, must begin at Cycle 1 Day 1 and continue every 21 days until disease progression or unacceptable toxicity.


Treatment: Other: quaratusugene ozeplasmid
Quaratusugene ozeplasmid is an experimental non-viral 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.

Treatment: Drugs: pembrolizumab
Pembrolizumab is a programmed death receptor-1 (PD-1) blocking antibody indicated for treatment of patients with metastatic NSCLC.

Treatment: Drugs: docetaxel
Docetaxel is a microtubule inhibitor indicated for locally advanced or metastatic NSCLC after platinum-based chemotherapy failure.

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

Treatment: Drugs: Investigator's Treatment of Choice
Treatment will be administered during 21-day treatment cycles. The investigator's treatment must not include investigational drugs or therapies.
Intervention code [1] 0 0
Treatment: Other
Intervention code [2] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Recommended Phase 2 Dose (RP2D) - Phase 1
Timepoint [1] 0 0
First 21-days at each dose level
Primary outcome [2] 0 0
Progression-free Survival (PFS) - Phase 2 Dose Expansion
Timepoint [2] 0 0
18 weeks
Primary outcome [3] 0 0
Progression-free Survival (PFS) - Phase 2 Randomized
Timepoint [3] 0 0
Approximately 8 months
Secondary outcome [1] 0 0
Progression-free Survival (PFS) - Phase 1
Timepoint [1] 0 0
Approximately 8 months
Secondary outcome [2] 0 0
Overall Survival (OS) - Phase 1
Timepoint [2] 0 0
Approximately 11 months
Secondary outcome [3] 0 0
Pharmacokinetics (PK) - Phase 1
Timepoint [3] 0 0
First 21-day treatment cycle
Secondary outcome [4] 0 0
Adverse Events (AEs) - Phase 2 Dose Expansion
Timepoint [4] 0 0
Approximately 9 months]
Secondary outcome [5] 0 0
Progression-free Survival (PFS) - Phase 2 Dose Expansion
Timepoint [5] 0 0
Approximately 8 months
Secondary outcome [6] 0 0
Overall Response Rate (ORR) - Phase 2 Dose Expansion
Timepoint [6] 0 0
Approximately 8 months
Secondary outcome [7] 0 0
Overall Survival (OS) - Phase 2 Dose Expansion
Timepoint [7] 0 0
Approximately 11 months
Secondary outcome [8] 0 0
Pharmacokinetics (PK) - Phase 2 Dose Expansion
Timepoint [8] 0 0
First 21-day treatment cycle
Secondary outcome [9] 0 0
Overall Response Rate (ORR) - Phase 2 Randomized
Timepoint [9] 0 0
Approximately 8 months
Secondary outcome [10] 0 0
Overall Survival (OS) - Phase 2 Randomized
Timepoint [10] 0 0
Approximately 11 months
Secondary outcome [11] 0 0
Disease Control Rate (DCR) - Phase 2 Randomized
Timepoint [11] 0 0
Approximately 8 months
Secondary outcome [12] 0 0
Adverse Events (AEs) - Phase 2 Randomized
Timepoint [12] 0 0
Approximately 9 months
Secondary outcome [13] 0 0
Pharmacokinetics (PK) - Phase 2 Randomized
Timepoint [13] 0 0
First 21-day treatment cycle

Eligibility
Key inclusion criteria
Patients will have their most recent archival tumor biopsy submitted to a central laboratory for IHC analysis.



1. Age =18 years.
2. Voluntarily signed an informed consent in accordance with institutional policies.
3. Histologically or cytologically documented NSCLC (SQ, NSQ, or mixed (adenosquamous) histology) with locally advanced or metastatic disease. Note: Any level of PD-L1 TPS is allowed.
4. Achieved clinical benefit to prior pembrolizumab or pembrolizumab/platinum-based chemotherapy for at least 3 months and subsequently progressed as confirmed by radiological tumor assessment per RECIST 1.1. Patients receiving pembrolizumab as a single agent must have additional therapy with a platinum-based chemotherapy prior to enrolling, but patients receiving pembrolizumab in combination with a platinum-based chemotherapy should have enrollment in this trial as the next treatment regimen. Chemotherapy is to be limited such that study treatment will be 2nd or 3rd line.
5. For Phase 2, patients must have measurable disease per RECIST 1.1.
6. Patients with genetic alterations with FDA-approved therapy (such as EGFR or anaplastic lymphoma kinase [ALK] mutations) must have disease progression after treatment with appropriate targeted therapy and must be eligible for immunotherapy as determined by the investigator.
7. ECOG performance status score from 0 to 1.
8. 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. Note: Placement of pleural catheter despite being a minor surgical procedure, may be performed <10 days prior to study enrollment.
9. Demonstrate adequate organ function, as determined by the following laboratory values obtained within 21 days prior to enrollment:

1. Absolute neutrophil count (ANC) =1,500/µL,
2. Platelets = 100,000/µL,
3. Hemoglobin =8.0 g/dL =2 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. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =1.5 × ULN,
9. Alkaline phosphatase =2.5 x ULN.
10. Stable cardiac condition with a left ventricular ejection fraction >40% within =21 days prior to enrollment.
11. Asymptomatic brain metastases, must meet ALL of the following criteria (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 corticosteroid 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.
12. Female patients of childbearing potential (FOCBP) must have a negative serum pregnancy test at screening (within 7 days of enrollment). Note: Non-childbearing potential is defined as greater than 1 year postmenopausal or surgically sterilized.
13. FOCBP and non-sterile male patients with female partner(s) of childbearing potential must agree to use 2 forms of contraception including 1 highly effective and 1 effective method beginning =2 weeks prior to enrollment through 4 months following the last dose of study treatment.
14. Male patients must agree to no sperm donation during study treatment and for an additional 4 months following the last dose of study treatment.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Unable to tolerate pembrolizumab treatment, leading to early treatment discontinuation or prolonged/frequent dosage modifications as determined by the investigator.
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 randomized portion only]).
4. Received prior systemic chemotherapy or monoclonal antibodies for the treatment of the participant's advanced or metastatic disease within 21 days 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. Note: Patients are permitted to have received palliative radiotherapy to an extremity provided at least 14 days has elapsed since completion of therapy, provided the patient received no more than 10 radiotherapy fractions and a dose no higher than 30 Gy to that site.
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 enrollment. Seasonal flu vaccines that do not contain live virus are permitted.
9. Has known active, symptomatic 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 (PO) or IV glucocorticoids to assist with management. Note: Lymphangitic spread of the NSCLC is not an exclusion criterion.
17. History of myocardial infarction or unstable angina within 6 months prior to enrollment.
18. Presence of pre-existing peripheral neuropathy that is =Grade 2 by NCI-CTCAE v5.0 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
30/03/2022
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/12/2025
Actual
Sample size
Target
180
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Florida
Country [2] 0 0
United States of America
State/province [2] 0 0
Louisiana
Country [3] 0 0
United States of America
State/province [3] 0 0
Missouri
Country [4] 0 0
United States of America
State/province [4] 0 0
New Jersey
Country [5] 0 0
United States of America
State/province [5] 0 0
Texas

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Genprex, Inc.
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
The purpose of this study is to determine the safety and efficacy of quaratusugene ozeplasmid (Reqorsa), in combination with pembrolizumab in patients with previously treated NSCLC. Quaratusugene ozeplasmid consists of non-viral lipid nanoparticles that encapsulate a DNA plasmid with the TUSC2 tumor suppressor gene, and is a systemic gene therapy.

The study will be conducted in 2 phases, a dose escalation 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 quaratusugene ozeplasmid in combination with pembrolizumab to determine the recommended Phase 2 dose (RP2D). Phase 2 will be comprised of a dose expansion portion and a randomized portion. In the dose expansion portion, patients will be enrolled and treated with quaratusugene ozeplasmid at the RP2D in combination with pembrolizumab. In the randomized portion, patients will be randomized to receive either the investigational treatment of quaratusugene ozeplasmid at the RP2D in combination with pembrolizumab or a control treatment of either docetaxel +/- ramucirumab or the investigator's treatment of choice.
Trial website
https://clinicaltrials.gov/study/NCT05062980
Trial related presentations / publications
Public notes
This record is viewable in the ANZCTR as it had previously listed Australia and/or New Zealand as a recruitment site, however these sites have since been removed

Contacts
Principal investigator
Name 0 0
Daniel Morgensztern, MD
Address 0 0
Washington University School of Medicine
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT05062980