ACCLAIM 2

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

Objective

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.

Study Arms

• Experimental: Investigational
• Active Comparator: Control

Eligibility

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.

NCT ID

NCT05062980