Quaratusugene Ozeplasmid (Reqorsa) and Osimertinib in Patients With Advanced Lung Cancer Who Progressed on Osimertinib (Acclaim-1)

A Phase 1/2 Open-Label, Dose-Escalation and Clinical Response Study of Quaratusugene Ozeplasmid in Combination With Osimertinib in Patients With Advanced, Metastatic EGFR-Mutant, Metastatic Non-Small Cell Lung Cancer

The purpose of this randomized study is to determine the safety and efficacy of quaratusugene ozeplasmid (Reqorsa) added to osimertinib in NSCLC patients with activating EGFR mutations who have progressed while on treatment with osimertinib. Quaratusugene ozeplasmid 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 comprise of a Phase 1 dose escalation and Phase 2 evaluations of safety and efficacy. In the Phase 1 dose escalation, patients will be enrolled in sequential cohorts treated with successively higher doses of quaratusugene ozeplasmid in combination with osimertinib. When the recommended Phase 2 dose (RP2D) is determined in Phase 1, Phase 2a will be initiated and patients will be enrolled in 2 parallel, non-randomized cohorts treated with quaratusugene ozeplasmid at the RP2D in combination with osimertinib. In Phase 2b, patients will be randomized to receive either quaratusugene ozeplasmid plus osimertinib or platinum-based chemotherapy.

Study Overview

• Status: Recruiting
• Conditions: Carcinoma, Non-Small Cell Lung
• Intervention / Treatment: Biological: quaratusugene ozeplasmid; Drug: osimertinib; Drug: Platinum-Based Chemotherapy

Detailed Description

Acclaim-1 is an open-label, multi-center, Phase 1/2 study evaluating quaratusugene ozeplasmid (Reqorsa) plus osimertinib (investigational arm) versus platinum-based chemotherapy (control arm) 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 quaratusugene ozeplasmid when given in combination with osimertinib will be identified.

Phase 2a: Once the RP2D of quaratusugene ozeplasmid is identified in Phase 1, 2 expansion cohorts will be enrolled to better characterize safety, tolerability, and preliminary anti-tumor activity of the combination therapy.

Phase 2b: Quaratusugene ozeplasmid 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 the investigational arm or the control arm in a 1 to 1 ratio and stratified based on prior local radiotherapy.

• Study Type: Interventional
• Enrollment (Estimated): 158
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Sr Director, Clinical Operations; Phone Number: 1-877-774-GNPX; Email: kcombs@genprex.com
• Study Contact Backup: Name: Chief Medical Officer; Phone Number: 1-877-774-GNPX; Email: mberger@genprex.com

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90067
      • Recruiting
      • Valkyrie Clinical Trials
      • Contact: Kristi Okino; Phone Number: 562-833-1483; Email: Kristi.okino@valkyrieclinicaltrials.com
      • Principal Investigator: David Berz, MD
  • Colorado
    • Lone Tree, Colorado, United States, 80124
      • Recruiting
      • Rocky Mountain Cancer Centers
      • Contact: Katherine Schleich; Phone Number: 35018 303-285-5018; Email: Katherine.schleich@usoncology.com
      • Contact: Joni Richman; Phone Number: 303-336-2181; Email: joni.richman@usoncology.com
      • Principal Investigator: Robert M. Jotte, MD
  • Illinois
    • Urbana, Illinois, United States, 61801
      • Recruiting
      • Carle Cancer Institute
      • Principal Investigator: Kendrith Rowland, MD
      • Contact: Hannah Parks; Phone Number: 217-326-3150; Email: Hannah.Parks@Carle.com
  • Maryland
    • Rockville, Maryland, United States, 20850
      • Recruiting
      • Maryland Oncology Hematology
      • Contact: Jake Brooks; Phone Number: 877-664-7724; Email: jake.brooks@usoncology.com
      • Principal Investigator: John M. Wallmark, MD
      • Contact: Missy Almand; Phone Number: 877-664-7724; Email: missy.almand@usoncology.com
  • Texas
    • Houston, Texas, United States, 77090
      • Recruiting
      • Millennium Oncology
      • Contact: John Waldron; Phone Number: 877-870-2640; Email: jwaldron@wmrad.com
      • Principal Investigator: Krishna K. Pachipala, MD
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Recruiting
      • Virginia Cancer Specialists
      • Principal Investigator: Alexander I. Spira, MD
      • Contact: Carrie Friedman, RN, BSN, OCN; Phone Number: 703-636-1473; Email: carrie.friedman@usoncology.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age ≥18 years.
2. Histologically or cytologically documented NSCLC.
3. Stage III or IV NSCLC or recurrent NSCLC that is not potentially curable by radiotherapy or surgery.
4. EGFR mutation-positive, based on results of most recent lung cancer tissue biopsy or evaluation of circulating tumor DNA. If the most recent EGFR mutation evaluation is by circulating tumor DNA, a previous lung cancer tissue biopsy must have demonstrated EGFR mutation.
5. Achieved clinical response to osimertinib for ≥4 months, which can be a response of stable disease. Must have a minimum of a 10-day osimertinib washout completed at the time of enrollment.

6. Must have radiological progression on osimertinib treatment and measurable disease per RECIST 1.1. Patients can have either asymptomatic disease or symptomatic disease. In addition, the following criteria must be met based on trial phase enrollment:

   Phase 2a:

   1. Cohort 1 must have progression on osimertinib treatment which must be the only systemic treatment for NSCLC.

   2. Cohort 2 must either have 1) progression on osimertinib in combination with pemetrexed and a platin (carboplatin or cisplatin) administered as initial treatment for metastatic NSCLC, or 2) have progression on single agent osimertinib administered as initial treatment for metastatic NSCLC, and then progression on pemetrexed and a platin (carboplatin or cisplatin), administered with or without osimertinib.

      Phase 2b:

   3. Must have progression on osimertinib treatment which must be the only systemic treatment for NSCLC.
7. Eastern Cooperative Oncology Group performance status (ECOG PS) 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 per Investigator assessment.

9. Asymptomatic brain metastases must meet ALL criteria of the following (a-d):

   1. No history of seizures in the preceding 6 months.
   2. Definitive treatment must be completed ≥21 days.
   3. Must be off steroids administered because of brain metastases or related symptoms for ≥7 days.
   4. Post-treatment imaging must demonstrate stability or regression of the brain metastases.
10. Patient must have and be willing to submit archival tumor biopsy for submissions to central laboratory for IHC analysis.
11. Absolute neutrophil count (ANC) >1500/mm3, platelet count >100,000/mm3 within ≤21 days.
12. Adequate renal function documented by serum creatinine of ≤1.5 mg/dL or calculated creatinine clearance >50 ml/min within ≤21 days.
13. Adequate hepatic function as documented by serum bilirubin <1.5 mg/dL and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 X upper limit of normal (ULN) within ≤21 days.
14. Stable cardiac condition with a left ventricular ejection fraction ≥40% within ≤21 days.
15. If female of childbearing potential (FOCBP), must have negative serum pregnancy test (serum beta-human chorionic gonadotropin [β-hCG]) within ≤7 days.
16. 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.
17. If male, must agree to no sperm donation during study treatment and for an additional 4 months following the last dose of study treatment.
18. Must have voluntarily signed an informed consent in accordance with institutional policies.

Exclusion Criteria:

1. Unable to tolerate osimertinib treatment, leading to early treatment discontinuation or prolonged/frequent dosage modifications as determined by the Investigator.
2. Received standard chemotherapy or monoclonal antibodies to treat NSCLC within ≤21 days.
3. Received prior gene therapy.
4. Other genetic characteristics (such as ALK, ROS, BRAF V600E mutations) which makes them a candidate for treatment with other approved targeted therapies.
5. Received radiotherapy to the skull, spine, thorax, or pelvis within ≤30 days.
6. Active systemic viral, bacterial, or fungal infection(s) requiring treatment.
7. 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.
8. History of myocardial infarction or unstable angina within ≤6 months.
9. Known human immunodeficiency virus (HIV) infection or has active hepatitis infection.
10. Female who is pregnant or breastfeeding.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Investigational; In Phase 1, Phase 2a and the investigational arm of Phase 2b, patients will receive their assigned dose of quaratusugene ozeplasmid (intravenous administration once every 21 days) plus osimertinib (80 mg fixed dose oral tablet taken daily starting on Day 1 through Day 21 of every 21-day treatment cycle) until disease progression or unacceptable toxicity.	Biological: quaratusugene ozeplasmid; Quaratusugene ozeplasmid is an experimental non-viral immunogene therapy utilizing the TUSC2 gene, designed to target cancer cells by interrupting cell signaling pathways that allow cancer cells to grow, reestablishing pathways that promote cancer cell death and modulating the immune response against cancer cells.; Other Names: Reqorsa; Drug: osimertinib; Osimertinib is a 3rd generation EGFR tyrosine kinase inhibitor (TKI) oral tablet administered daily, as indicated for treatment of patients with metastatic NSCLC whose tumors have EGFR genetic deletions or mutations.; Other Names: Tagrisso
Active Comparator: Control; In the control arm of Phase 2b, patients will receive platinum-based chemotherapy until disease progression or unacceptable toxicity.	Drug: Platinum-Based Chemotherapy; Cisplatin and carboplatin are intravenously administered platinum agents that are combined with other cytotoxic chemotherapy agents such as pemetrexed.; Other Names: cisplatin; carboplatin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recommended Phase 2 Dose (RP2D) - Phase 1	RP2D, which will be the maximum tolerated dose (MTD) or, if the MTD is not defined by the safety data, RP2D will be determined based on an integrated assessment of all available clinical safety and preliminary efficacy data.	First 21-day treatment cycle for each dose level cohort
Overall Response Rate (ORR) - Phase 2a	ORR (complete response [CR]+ partial response [PR]) according to RECIST using best overall response from baseline to disease progression or death.	Approximately 9 months
Progression-free Survival (PFS) - Phase 2b	PFS from randomization to disease progression or death. PFS according to RECIST.	Approximately 9 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free Survival (PFS) - Phase 1	PFS from first dose to disease progression or death. PFS according to RECIST.	Approximately 9 months
Overall Response Rate (ORR) - Phase 1	ORR (CR+ PR) according to RECIST using best overall response from baseline to disease progression or death.	Approximately 9 months
Pharmacokinetics (PK) of Quaratusugene Ozeplasmid - Phase 1	Concentration of quaratusugene ozeplasmid in whole blood samples.	First 21-day treatment cycle
Progression-free Survival (PFS) - Phase 2a	PFS from first dose to disease progression or death. PFS according to RECIST.	Approximately 9 months
Time to Progression (TTP) - Phase 2a	TTP from first dose to disease progression. TTP according to RECIST.	Approximately 9 months
Overall Survival (OS) - Phase 2a	OS from first dose until death or discontinuation due to withdrawal of consent.	Approximately 21 months
Overall Response Rate (ORR) - Phase 2b	ORR (CR+ PR) according to RECIST using best overall response from baseline to disease progression or death.	Approximately 9 months
Duration of Response (DOR) - Phase 2b	DOR (CR + PR) according to RECIST from response to disease progression.	Approximately 9 months
Overall Survival (OS) - Phase 2b	OS from randomization to death or discontinuation due to withdrawal of consent.	Approximately 21 months
Incidence of Adverse Events - Phase 2b	Treatment-related adverse events (AEs) graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events.	Approximately 10 months
Pharmacokinetics (PK) of Quaratusugene Ozeplasmid - Phase 2b	Concentration of quaratusugene ozeplasmid in whole blood samples.	First 21-day treatment cycle

Collaborators and Investigators

• Sponsor: Genprex, Inc.
• Investigators: Study Director: Mark S. Berger, MD, Genprex, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): September 3, 2021
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: July 22, 2020
• First Submitted That Met QC Criteria: July 22, 2020
• First Posted (Actual): July 27, 2020

Study Record Updates

• Last Update Posted (Estimated): February 29, 2024
• Last Update Submitted That Met QC Criteria: February 27, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: NSCLC; Tagrisso; Gene therapy; osimertinib; Epidermal growth factor receptor mutation (EGFR); Tumor suppressor gene 2 (TUSC2); Lipid nanoparticle (LNP); FUS1-nanoparticles; Reqorsa; quaratusugene ozeplasmid
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Carboplatin; Cisplatin; Osimertinib
• Other Study ID Numbers: ONC-003

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No