Clinical Trial 21228

• Overview

  Study 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 (Acclaim 2)

  Summary:

  The purpose of this randomized study is to determine the safety and efficacy of Reqorsa (quaratusugene ozeplasmid, formerly known as GPX-001), in combination with pembrolizumab in patients with previously treated NSCLC. 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.

  Objective:

  Primary Objectives Phase 1: Identify maximum tolerated dose (MTD) of GPX-001 when given in combination with pembrolizumab and to evaluate the safety profile of this combination. Phase 2: Compare progression-free survival (PFS) of the GPX-001 plus pembrolizumab combination versus active comparator. Secondary Objectives Phase 2: Determine whether overall survival (OS) of GPX-001 in combination with pembrolizumab prolongs patient survival compared to active comparator. Evaluate the tolerability and toxicity of GPX-001 in combination with pembrolizumab.

• Treatments

  Therapies:

  Chemotherapy (NOS); Immunotherapy

  Medications:

  IMC-1121B (Ramucirumab); Pembrolizumab (Keytruda); Ramucirumab (); Reqorsa (Quaratusugene Ozeplasmid); Taxotere (docetaxel); docetaxel ()

• Inclusion Criteria

  Inclusion Criteria:
  • Adults 18 years of age or older
  • Voluntarily signed an informed consent
  • Histologically or cytologically documented NSCLC with locally advanced or metastatic stage IV disease. Note: Any level of PD-L1 TPS is allowed.
  • Achieved clinical benefit to prior pembrolizumab/platinum-based chemotherapy for at least 3 months and subsequently progressed with 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.
  • Eastern Cooperative Oncology Arm (ECOG) performance score from 0 to 1.
  • Must be 28 days or more beyond major surgical procedures such as thoracotomy, laparotomy, or joint replacement, and must be 10 days or more 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.
  • Demonstrate adequate organ function, as determined by laboratory values defined in protocol obtained within 7 days prior to enrollment.
  • Stable cardiac condition with a left ventricular ejection fraction > 40%.within 21 days prior to enrollment.
  • If treated, asymptomatic brain metastases are present, must meet ALL criteria listed (a-d): A. No history of seizures in the preceding 6 months, B. Definitive treatment must be completed ≥ 4 weeks prior to enrollment, C. Stopped corticosteroid treatments administered because of brain metastases or related symptoms for ≥ 2 weeks prior to enrollment, D. Post-treatment imaging must demonstrate stability or regression of the brain metastases.
  • 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.
  • 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.
  • 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

  Exclusion Criteria:
  • Unable to tolerate pembrolizumab treatment, leading to early treatment discontinuation or prolonged/ frequent dosage modifications.
  • 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 1 month of study enrollment
  • Received prior gene therapy.
  • Received any radiotherapy to the skull, spine, thorax or pelvis within 21 days of study enrollment.
  • Expected to require any other form of antineoplastic therapy while participating in the study.
  • Received a live-virus vaccination within 1 month of planned treatment start. Seasonal flu vaccines that do not contain live virus are permitted.
  • Has known active 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.
  • History of symptomatic interstitial lung disease or pneumonitis that required oral or IV glucocorticoids to assist with management.
  • History of myocardial infarction or unstable angina within the past 6 months.
  • 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.
  • 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.
  • Known human immunodeficiency virus (HIV) infection or has active hepatitis infection.
  • Female patients who are pregnant or breastfeeding.

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