Lung Cancer Clinical Trial
Reqorsa (Quaratusugene Ozeplasmid) and Osimertinib in Patients With Advanced Lung Cancer Who Progressed on Osimertinib
The purpose of this randomized study is to determine the safety and efficacy of Reqorsa (quaratusugene ozeplasmid, formerly known as GPX-001) added to osimertinib in NSCLC patients with activating EGFR mutations who have progressed while on treatment with osimertinib. 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 for cancer.
The study will be conducted in 2 phases, a dose escalation and expansion 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 Reqorsa in combination with osimertinib. When the recommended Phase 2 dose (RP2D) is determined, additional patients will be enrolled in an expansion cohort. In Phase 2, patient will be randomized to receive Reqorsa plus osimertinib or osimertinib alone.
Acclaim-1 is an open-label, multi-center, Phase 1/2 study evaluating Reqorsa (quaratusugene ozeplasmid) plus osimertinib versus monotherapy osimertinib in patients with advanced metastatic or recurrent NSCLC.
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 a safety review committee.
Phase 1 - Dose Escalation: The RP2D of Reqorsa when given in combination with osimertinib will be identified. Once the RP2D is identified an expansion cohort will be enrolled to better characterize safety, tolerability, and preliminary anti-tumor activity.
Phase 2: Reqorsa in combination with osimertinib will be further evaluated using the RP2D identified in Phase 1. Patients may receive local therapy, such as radiation therapy, to progressing lesions prior to enrollment. 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.
Histologically or cytologically documented non-small cell lung cancer (NSCLC).
Stage III or IV NSCLC or recurrent NSCLC that is not potentially curable by radiotherapy or surgery whether or not patient has received prior chemotherapy.
EGFR mutation-positive as detected by an FDA-approved test, based on results of most recent biopsy.
Achieved clinical response to osimertinib for ≥4 months.
Must have radiological progression on or after treatment with osimertinib and can have either asymptomatic disease or symptomatic disease. For Phase 2 only, eligibility for patients with symptomatic disease is restricted to those with limited metastasis (≤5 metastases).
Eastern Cooperative Oncology Arm (ECOG) performance 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.
If asymptomatic brain metastases are present must meet ALL criteria listed:
No history of seizures in the preceding 6 months.
Definitive treatment must be completed ≥21 days.
Patients must be off steroids administered because of brain metastases or related symptoms for ≥7 days.
Post-treatment imaging must demonstrate stability or regression of the brain metastases.
ANC >1500/mm3, platelet count >100,000/mm3 within ≤21 days.
Adequate renal function documented by serum creatinine of ≤1.5 mg/dL or calculated creatinine clearance >50 ml/min within ≤21 days.
Adequate hepatic function as documented by serum bilirubin <1.5 mg/dL and AST and ALT ≤2.5 X upper limit of normal (ULN) within ≤21 days.
Stable cardiac condition with a left ventricular ejection fraction ≥40% within ≤21 days.
If female of childbearing potential, must have negative serum pregnancy test (serum β-hCG) within ≤7 days.
Must agree to 2 forms of contraception including 1 highly effective and 1 effective methods during the study period and for 4 months following the last dose of study treatment.
If male, must agree to no sperm donation during study treatment and for an additional 4 months following the last dose of study treatment.
Must have voluntarily signed an informed consent in accordance with institutional policies.
Unable to tolerate osimertinib treatment, leading to early treatment discontinuation or prolonged/frequent dosage modifications.
Received standard chemotherapy or monoclonal antibodies to treat NSCLC within ≤21 days.
Received prior gene therapy.
Other genetic characteristics (such as ALK, ROS, BRAF V600E mutations) which makes them a candidate for treatment with other approved targeted therapies.
Received radiotherapy to the skull, spine, thorax, or pelvis within ≤30 days.
Active systemic viral, bacterial, or fungal infection(s) requiring treatment.
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.
History of myocardial infarction or unstable angina within ≤6 months.
Known human immunodeficiency virus (HIV) infection or has active hepatitis infection.
Female who is pregnant or breastfeeding.
Check Your Eligibility
Let’s see if you might be eligible for this study.
What is your age and gender ?
There are 5 Locations for this study
How clear is this clinincal trial information?
Introducing, the Journey Bar
Use this bar to access information about the steps in your cancer journey.