Quaratusugene Ozeplasmid (Reqorsa) in Combination With Pembrolizumab in Previously Treated Non-Small Lung Cancer

NCT05062980 | Terminated Phase 1 FDA Drug

• 1 other identifier: ONC-004
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 6

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.

Conditions

Non Small Cell Lung Cancer

Keywords

Tumor suppressor gene 2 (TUSC2); Lipid nanoparticle (LNP); pembrolizumab; Keytruda; Gene therapy; NSCLC; docetaxel; Reqorsa; Acclaim-2; quaratusugene ozeplasmid

Outcome Measures

Primary Outcomes (3)

• Recommended Phase 2 Dose (RP2D) - Phase 1

  RP2D which will be the 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, PK, and preliminary efficacy data.

  First 21-days at each dose level

• Progression-free Survival (PFS) - Phase 2 Dose Expansion

  PFS rate at 18 weeks after first dose of study treatment. PFS according to RECIST.

  18 weeks

• Progression-free Survival (PFS) - Phase 2 Randomized

  PFS from randomization to disease progression or death. PFS according to RECIST.

  Approximately 8 months

Secondary Outcomes (13)

• Progression-free Survival (PFS) - Phase 1

  Approximately 8 months

• Overall Survival (OS) - Phase 1

  Approximately 11 months

• Pharmacokinetics (PK) - Phase 1

  First 21-day treatment cycle

• Adverse Events (AEs) - Phase 2 Dose Expansion

  Approximately 9 months]

• Progression-free Survival (PFS) - Phase 2 Dose Expansion

  Approximately 8 months

Study Arms (2)

Investigational

EXPERIMENTAL

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.

Biological: quaratusugene ozeplasmid; Drug: pembrolizumab

Control

ACTIVE COMPARATOR

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.

Drug: docetaxel; Drug: ramucirumab; Drug: Investigator's Treatment of Choice

Interventions

quaratusugene ozeplasmid BIOLOGICAL

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.

Also known as: Reqorsa

Investigational

pembrolizumab DRUG

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

Also known as: Keytruda

Investigational

docetaxel DRUG

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

Also known as: Taxotere

Control

ramucirumab DRUG

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.

Also known as: Cyramza

Control

Investigator's Treatment of Choice DRUG

Treatment will be administered during 21-day treatment cycles. The investigator's treatment must not include investigational drugs or therapies.

Control

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥18 years.
• Voluntarily signed an informed consent in accordance with institutional policies.
• 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.
• 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.
• For Phase 2, patients must have measurable disease per RECIST 1.1.
• 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.
• ECOG performance status 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. Note: Placement of pleural catheter despite being a minor surgical procedure, may be performed \<10 days prior to study enrollment.
• Demonstrate adequate organ function, as determined by the following laboratory values obtained within 21 days prior to enrollment:
• Absolute neutrophil count (ANC) ≥1,500/μL,
• Platelets ≥ 100,000/μL,
• Hemoglobin ≥8.0 g/dL ≥2 weeks without transfusions,
• 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,
• 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,
• Creatinine ≤1.5 × ULN OR calculated creatinine clearance (CrCl) ≥60 mL/min for patients with creatinine levels \>1.5 × ULN,

You may not qualify if:

• Unable to tolerate pembrolizumab treatment, leading to early treatment discontinuation or prolonged/frequent dosage modifications as determined by the investigator.
• Hypersensitivity to docetaxel or polysorbate 80 (Phase 2 only).
• Patients at risk of tumor lysis syndrome (e.g., renal impairment, hyperuricemia, bulky tumor \[Phase 2 randomized portion only\]).
• Received prior systemic chemotherapy or monoclonal antibodies for the treatment of the participant's advanced or metastatic disease within 21 days of study enrollment.
• Received prior gene therapy.
• 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.
• Expected to require any other form of antineoplastic therapy while participating in the study.
• Received a live-virus vaccination within 1 month of enrollment. Seasonal flu vaccines that do not contain live virus are permitted.
• Has known active, symptomatic CNS metastases and/or carcinomatous meningitis.
• Active, known, or suspected autoimmune disease.
• Active systemic viral, bacterial, or fungal infections(s) requiring treatment.
• 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.
• 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.
• Active concurrent malignancies, i.e., cancers other than NSCLC.
• Has a second, concurrent, untreated malignancy.

Sponsors & Collaborators

• Genprex, Inc.: lead

Study Sites (6)

Moffitt Cancer Center - Magnolia Campus

Tampa, Florida, 33612, United States

Location

Ochsner Clinic Foundation

New Orleans, Louisiana, 70121, United States

Location

Washington University School of Medicine - Siteman Cancer Center

St Louis, Missouri, 63110, United States

Location

The Valley Hospital - Luckow Pavilion

Paramus, New Jersey, 07652, United States

Location

Mary Crowley Cancer Research

Dallas, Texas, 75230, United States

Location

Millennium Oncology

Houston, Texas, 77090, United States

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

pembrolizumab; Docetaxel; Ramucirumab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Daniel Morgensztern, MD

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Phase 1: 3+3 dose escalation to identify RP2D. Phase 2: RP2D expansion cohort followed by parallel randomization in a 2:1 ratio to either investigational arm or control arm.

Study Record Dates

• First Submitted: September 20, 2021
• First Posted: September 30, 2021
• Study Start: March 30, 2022
• Primary Completion: February 3, 2025
• Study Completion: February 3, 2025
• Last Updated: February 20, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (6)