<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT04486833</url>
  </required_header>
  <id_info>
    <org_study_id>ONC-003</org_study_id>
    <nct_id>NCT04486833</nct_id>
  </id_info>
  <brief_title>Quaratusugene Ozeplasmid (Reqorsa) and Osimertinib in Patients With Advanced Lung Cancer Who Progressed on Osimertinib</brief_title>
  <acronym>Acclaim-1</acronym>
  <official_title>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</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Genprex, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Genprex, Inc.</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this randomized study is to determine the safety and efficacy of quaratusugene&#xD;
      ozeplasmid (Reqorsa) added to osimertinib in NSCLC patients with activating EGFR mutations&#xD;
      who have progressed while on treatment with osimertinib. Quaratusugene ozeplasmid consists of&#xD;
      non-viral lipid nanoparticles that encapsulate a DNA plasmid with the TUSC2 tumor suppressor&#xD;
      gene and is the first systemic gene therapy for cancer.&#xD;
&#xD;
      The study will comprise of a Phase 1 dose escalation and Phase 2 evaluations of safety and&#xD;
      efficacy. In the Phase 1 dose escalation, patients will be enrolled in sequential cohorts&#xD;
      treated with successively higher doses of quaratusugene ozeplasmid in combination with&#xD;
      osimertinib. When the recommended Phase 2 dose (RP2D) is determined in Phase 1, Phase 2a will&#xD;
      be initiated and patients will be enrolled in 2 parallel, non-randomized cohorts treated with&#xD;
      quaratusugene ozeplasmid at the RP2D in combination with osimertinib. In Phase 2b, patients&#xD;
      will be randomized to receive either quaratusugene ozeplasmid plus osimertinib or&#xD;
      platinum-based chemotherapy.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Acclaim-1 is an open-label, multi-center, Phase 1/2 study evaluating quaratusugene ozeplasmid&#xD;
      (Reqorsa) plus osimertinib (investigational arm) versus platinum-based chemotherapy (control&#xD;
      arm) in patients with advanced metastatic or recurrent NSCLC.&#xD;
&#xD;
      Toxicities will be assessed by the Investigator using United States National Cancer Institute&#xD;
      (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 5.0. Serious Adverse&#xD;
      Events and Dose Limiting Toxicities (DLT) will be reviewed by a Safety Review Committee.&#xD;
&#xD;
      Phase 1 - Dose Escalation: The RP2D of quaratusugene ozeplasmid when given in combination&#xD;
      with osimertinib will be identified.&#xD;
&#xD;
      Phase 2a: Once the RP2D of quaratusugene ozeplasmid is identified in Phase 1, 2 expansion&#xD;
      cohorts will be enrolled to better characterize safety, tolerability, and preliminary&#xD;
      anti-tumor activity of the combination therapy.&#xD;
&#xD;
      Phase 2b: Quaratusugene ozeplasmid in combination with osimertinib will be further evaluated&#xD;
      using the RP2D identified in Phase 1. Patients may receive local therapy, such as radiation&#xD;
      therapy, to progressing lesions prior to enrollment. Patients will be randomized to receive&#xD;
      either the investigational arm or the control arm in a 1 to 1 ratio and stratified based on&#xD;
      prior local radiotherapy.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">September 3, 2021</start_date>
  <completion_date type="Anticipated">December 2027</completion_date>
  <primary_completion_date type="Anticipated">December 2026</primary_completion_date>
  <phase>Phase 1/Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Sequential Assignment</intervention_model>
    <intervention_model_description>Phase 1: 3+3 dose escalation to identify RP2D.&#xD;
Phase 2: RP2D further evaluated in Phase 2a followed by parallel randomization in a 1:1 ratio to either investigational arm or control arm.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Recommended Phase 2 Dose (RP2D) - Phase 1</measure>
    <time_frame>First 21-day treatment cycle for each dose level cohort</time_frame>
    <description>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.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Overall Response Rate (ORR) - Phase 2a</measure>
    <time_frame>Approximately 9 months</time_frame>
    <description>ORR (complete response [CR]+ partial response [PR]) according to RECIST using best overall response from baseline to disease progression or death.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Progression-free Survival (PFS) - Phase 2b</measure>
    <time_frame>Approximately 9 months</time_frame>
    <description>PFS from randomization to disease progression or death. PFS according to RECIST.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Progression-free Survival (PFS) - Phase 1</measure>
    <time_frame>Approximately 9 months</time_frame>
    <description>PFS from first dose to disease progression or death. PFS according to RECIST.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Response Rate (ORR) - Phase 1</measure>
    <time_frame>Approximately 9 months</time_frame>
    <description>ORR (CR+ PR) according to RECIST using best overall response from baseline to disease progression or death.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics (PK) of Quaratusugene Ozeplasmid - Phase 1</measure>
    <time_frame>First 21-day treatment cycle</time_frame>
    <description>Concentration of quaratusugene ozeplasmid in whole blood samples.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression-free Survival (PFS) - Phase 2a</measure>
    <time_frame>Approximately 9 months</time_frame>
    <description>PFS from first dose to disease progression or death. PFS according to RECIST.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Progression (TTP) - Phase 2a</measure>
    <time_frame>Approximately 9 months</time_frame>
    <description>TTP from first dose to disease progression. TTP according to RECIST.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival (OS) - Phase 2a</measure>
    <time_frame>Approximately 21 months</time_frame>
    <description>OS from first dose until death or discontinuation due to withdrawal of consent.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Response Rate (ORR) - Phase 2b</measure>
    <time_frame>Approximately 9 months</time_frame>
    <description>ORR (CR+ PR) according to RECIST using best overall response from baseline to disease progression or death.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of Response (DOR) - Phase 2b</measure>
    <time_frame>Approximately 9 months</time_frame>
    <description>DOR (CR + PR) according to RECIST from response to disease progression.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival (OS) - Phase 2b</measure>
    <time_frame>Approximately 21 months</time_frame>
    <description>OS from randomization to death or discontinuation due to withdrawal of consent.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of Adverse Events - Phase 2b</measure>
    <time_frame>Approximately 10 months</time_frame>
    <description>Treatment-related adverse events (AEs) graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics (PK) of Quaratusugene Ozeplasmid - Phase 2b</measure>
    <time_frame>First 21-day treatment cycle</time_frame>
    <description>Concentration of quaratusugene ozeplasmid in whole blood samples.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">158</enrollment>
  <condition>Carcinoma, Non-Small Cell Lung</condition>
  <arm_group>
    <arm_group_label>Investigational</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>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.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>In the control arm of Phase 2b, patients will receive platinum-based chemotherapy until disease progression or unacceptable toxicity.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>quaratusugene ozeplasmid</intervention_name>
    <description>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.</description>
    <arm_group_label>Investigational</arm_group_label>
    <other_name>Reqorsa</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>osimertinib</intervention_name>
    <description>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.</description>
    <arm_group_label>Investigational</arm_group_label>
    <other_name>Tagrisso</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Platinum-Based Chemotherapy</intervention_name>
    <description>Cisplatin and carboplatin are intravenously administered platinum agents that are combined with other cytotoxic chemotherapy agents such as pemetrexed.</description>
    <arm_group_label>Control</arm_group_label>
    <other_name>cisplatin</other_name>
    <other_name>carboplatin</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Age ≥18 years.&#xD;
&#xD;
          2. Histologically or cytologically documented NSCLC.&#xD;
&#xD;
          3. Stage III or IV NSCLC or recurrent NSCLC that is not potentially curable by&#xD;
             radiotherapy or surgery.&#xD;
&#xD;
          4. EGFR mutation-positive, based on results of most recent lung cancer tissue biopsy or&#xD;
             evaluation of circulating tumor DNA. If the most recent EGFR mutation evaluation is by&#xD;
             circulating tumor DNA, a previous lung cancer tissue biopsy must have demonstrated&#xD;
             NSCLC.&#xD;
&#xD;
          5. Achieved clinical response to osimertinib for ≥4 months, which can be a response of&#xD;
             stable disease. Must have a minimum of a 10-day osimertinib washout completed at the&#xD;
             time of enrollment.&#xD;
&#xD;
          6. Must have radiological progression on osimertinib treatment and can have either&#xD;
             asymptomatic disease or symptomatic disease. In addition, the following criteria must&#xD;
             be met based on trial phase enrollment:&#xD;
&#xD;
             Phase 1 Expansion portion:&#xD;
&#xD;
               1. Must have measurable disease per RECIST 1.1.&#xD;
&#xD;
               2. Cohort 1 must have progression on osimertinib treatment which must be the only&#xD;
                  systemic treatment for NSCLC.&#xD;
&#xD;
               3. Cohort 2 must either have 1) progression on osimertinib in combination with&#xD;
                  pemetrexed and a platin (carboplatin or cisplatin) administered as initial&#xD;
                  treatment for metastatic NSCLC, or 2) have progression on single agent&#xD;
                  osimertinib administered as initial treatment for metastatic NSCLC, and then&#xD;
                  progression on pemetrexed and a platin (carboplatin or cisplatin), administered&#xD;
                  with osimertinib, or pemetrexed and osimertinib. May have received prior&#xD;
                  bevacizumab in combination with the osimertinib containing regimens noted&#xD;
                  previously. No other prior systemic treatments are allowed.&#xD;
&#xD;
                  Phase 2:&#xD;
&#xD;
               4. Must have measurable disease per RECIST 1.1.&#xD;
&#xD;
               5. Must have progression on osimertinib treatment which must be the only systemic&#xD;
                  treatment for NSCLC.&#xD;
&#xD;
               6. Eligibility for patients with symptomatic disease is restricted to those with&#xD;
                  limited metastasis (≤5 metastases).&#xD;
&#xD;
          7. Eastern Cooperative Oncology Group performance status (ECOG PS) score from 0 to 1.&#xD;
&#xD;
          8. Must be ≥28 days beyond major surgical procedures such as thoracotomy, laparotomy, or&#xD;
             joint replacement, and must be ≥10 days beyond minor surgical procedures such as&#xD;
             biopsy of subcutaneous tumors, pleuroscopy, etc., and must not have evidence of wound&#xD;
             dehiscence, active wound infection, or comparable major residual complications of the&#xD;
             surgery per investigator assessment.&#xD;
&#xD;
          9. Asymptomatic brain metastases must meet ALL criteria of the following:&#xD;
&#xD;
               1. No history of seizures in the preceding 6 months.&#xD;
&#xD;
               2. Definitive treatment must be completed ≥21 days.&#xD;
&#xD;
               3. Must be off steroids administered because of brain metastases or related symptoms&#xD;
                  for ≥7 days.&#xD;
&#xD;
               4. Post-treatment imaging must demonstrate stability or regression of the brain&#xD;
                  metastases.&#xD;
&#xD;
         10. Absolute neutrophil count (ANC) &gt;1500/mm3, platelet count &gt;100,000/mm3 within ≤21&#xD;
             days.&#xD;
&#xD;
         11. Adequate renal function documented by serum creatinine of ≤1.5 mg/dL or calculated&#xD;
             creatinine clearance &gt;50 ml/min within ≤21 days.&#xD;
&#xD;
         12. Adequate hepatic function as documented by serum bilirubin &lt;1.5 mg/dL and aspartate&#xD;
             aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 X upper limit of normal&#xD;
             (ULN) within ≤21 days.&#xD;
&#xD;
         13. Stable cardiac condition with a left ventricular ejection fraction ≥40% within ≤21&#xD;
             days.&#xD;
&#xD;
         14. If female of childbearing potential (FOCBP), must have negative serum pregnancy test&#xD;
             (serum beta-human chorionic gonadotropin [β-hCG]) within ≤7 days.&#xD;
&#xD;
         15. Must agree to use 2 forms of contraception including 1 highly effective and 1&#xD;
             effective methods (defined in Section 5.3) during the study period and for 4 months&#xD;
             following the last dose of study treatment.&#xD;
&#xD;
         16. If male, must agree to no sperm donation during study treatment and for an additional&#xD;
             4 months following the last dose of study treatment.&#xD;
&#xD;
         17. Must have voluntarily signed an informed consent in accordance with institutional&#xD;
             policies.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Unable to tolerate osimertinib treatment, leading to early treatment discontinuation&#xD;
             or prolonged/frequent dosage modifications as determined by the investigator.&#xD;
&#xD;
          2. Received standard chemotherapy or monoclonal antibodies to treat NSCLC within ≤21&#xD;
             days.&#xD;
&#xD;
          3. Received prior gene therapy.&#xD;
&#xD;
          4. Other genetic characteristics (such as ALK, ROS, BRAF V600E mutations) which makes the&#xD;
             patient a candidate for treatment with other approved targeted therapies.&#xD;
&#xD;
          5. Received radiotherapy to the skull, spine, thorax, or pelvis within ≤30 days.&#xD;
&#xD;
          6. Active systemic viral, bacterial, or fungal infection(s) requiring treatment.&#xD;
&#xD;
          7. Serious concurrent illness or psychological, familial, sociological, geographical, or&#xD;
             other concomitant conditions that, in the opinion of the investigator, would not&#xD;
             permit adequate follow-up and compliance with the study protocol.&#xD;
&#xD;
          8. History of myocardial infarction or unstable angina within ≤6 months.&#xD;
&#xD;
          9. Known human immunodeficiency virus (HIV) infection or has active hepatitis infection.&#xD;
&#xD;
         10. Female who is pregnant or breastfeeding.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Mark S. Berger, MD</last_name>
    <role>Study Director</role>
    <affiliation>Genprex, Inc.</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Sr Director, Clinical Operations</last_name>
    <phone>1-877-774-GNPX</phone>
    <email>kcombs@genprex.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Chief Medical Officer</last_name>
    <phone>1-877-774-GNPX</phone>
    <email>mberger@genprex.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Valkyrie Clinical Trials</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90067</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Kristi Okino</last_name>
      <phone>562-833-1483</phone>
      <email>Kristi.okino@valkyrieclinicaltrials.com</email>
    </contact>
    <investigator>
      <last_name>David Berz, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Rocky Mountain Cancer Centers</name>
      <address>
        <city>Lone Tree</city>
        <state>Colorado</state>
        <zip>80124</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Katherine Schleich</last_name>
      <phone>303-285-5018</phone>
      <phone_ext>35018</phone_ext>
      <email>Katherine.schleich@usoncology.com</email>
    </contact>
    <contact_backup>
      <last_name>Joni Richman</last_name>
      <phone>303-336-2181</phone>
      <email>joni.richman@usoncology.com</email>
    </contact_backup>
    <investigator>
      <last_name>Robert M. Jotte, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Maryland Oncology Hematology</name>
      <address>
        <city>Rockville</city>
        <state>Maryland</state>
        <zip>20850</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Missy Almand</last_name>
      <phone>877-664-7724</phone>
      <email>missy.almand@usoncology.com</email>
    </contact>
    <contact_backup>
      <last_name>Jake Brooks</last_name>
      <phone>877-664-7724</phone>
      <email>jake.brooks@usoncology.com</email>
    </contact_backup>
    <investigator>
      <last_name>John M. Wallmark, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Millennium Oncology</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77090</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>John Waldron</last_name>
      <phone>877-870-2640</phone>
      <email>jwaldron@wmrad.com</email>
    </contact>
    <investigator>
      <last_name>Krishna K. Pachipala, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Virginia Cancer Specialists</name>
      <address>
        <city>Fairfax</city>
        <state>Virginia</state>
        <zip>22031</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Carrie Friedman, RN, BSN, OCN</last_name>
      <phone>703-636-1473</phone>
      <email>carrie.friedman@usoncology.com</email>
    </contact>
    <investigator>
      <last_name>Alexander I. Spira, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>June 2023</verification_date>
  <study_first_submitted>July 22, 2020</study_first_submitted>
  <study_first_submitted_qc>July 22, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 27, 2020</study_first_posted>
  <last_update_submitted>June 1, 2023</last_update_submitted>
  <last_update_submitted_qc>June 1, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">June 5, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Epidermal growth factor receptor mutation (EGFR)</keyword>
  <keyword>osimertinib</keyword>
  <keyword>Tumor suppressor gene 2 (TUSC2)</keyword>
  <keyword>Lipid nanoparticle (LNP)</keyword>
  <keyword>Gene therapy</keyword>
  <keyword>Tagrisso</keyword>
  <keyword>FUS1-nanoparticles</keyword>
  <keyword>NSCLC</keyword>
  <keyword>Reqorsa</keyword>
  <keyword>quaratusugene ozeplasmid</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Carcinoma, Non-Small-Cell Lung</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cisplatin</mesh_term>
    <mesh_term>Carboplatin</mesh_term>
    <mesh_term>Osimertinib</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04486833
org study id: ONC-003
nct id: NCT04486833
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
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.
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.
allocation: Randomized
intervention model: Sequential Assignment
intervention model description: Phase 1: 3+3 dose escalation to identify RP2D.
Phase 2: RP2D further evaluated in Phase 2a followed by parallel randomization in a 1:1 ratio to either investigational arm or control arm.
primary purpose: Treatment
masking: None (Open Label)
measure: Recommended Phase 2 Dose (RP2D) - Phase 1
time frame: First 21-day treatment cycle for each dose level cohort
description: 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.
measure: Overall Response Rate (ORR) - Phase 2a
time frame: Approximately 9 months
description: ORR (complete response [CR]+ partial response [PR]) according to RECIST using best overall response from baseline to disease progression or death.
measure: Progression-free Survival (PFS) - Phase 2b
time frame: Approximately 9 months
description: PFS from randomization to disease progression or death. PFS according to RECIST.
measure: Progression-free Survival (PFS) - Phase 1
time frame: Approximately 9 months
description: PFS from first dose to disease progression or death. PFS according to RECIST.
measure: Overall Response Rate (ORR) - Phase 1
time frame: Approximately 9 months
description: ORR (CR+ PR) according to RECIST using best overall response from baseline to disease progression or death.
measure: Pharmacokinetics (PK) of Quaratusugene Ozeplasmid - Phase 1
time frame: First 21-day treatment cycle
description: Concentration of quaratusugene ozeplasmid in whole blood samples.
measure: Progression-free Survival (PFS) - Phase 2a
time frame: Approximately 9 months
description: PFS from first dose to disease progression or death. PFS according to RECIST.
measure: Time to Progression (TTP) - Phase 2a
time frame: Approximately 9 months
description: TTP from first dose to disease progression. TTP according to RECIST.
measure: Overall Survival (OS) - Phase 2a
time frame: Approximately 21 months
description: OS from first dose until death or discontinuation due to withdrawal of consent.
measure: Overall Response Rate (ORR) - Phase 2b
time frame: Approximately 9 months
description: ORR (CR+ PR) according to RECIST using best overall response from baseline to disease progression or death.
measure: Duration of Response (DOR) - Phase 2b
time frame: Approximately 9 months
description: DOR (CR + PR) according to RECIST from response to disease progression.
measure: Overall Survival (OS) - Phase 2b
time frame: Approximately 21 months
description: OS from randomization to death or discontinuation due to withdrawal of consent.
measure: Incidence of Adverse Events - Phase 2b
time frame: Approximately 10 months
description: Treatment-related adverse events (AEs) graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events.
measure: Pharmacokinetics (PK) of Quaratusugene Ozeplasmid - Phase 2b
time frame: First 21-day treatment cycle
description: Concentration of quaratusugene ozeplasmid in whole blood samples.
arm group label: Investigational
arm group type: Experimental
description: 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.
arm group label: Control
arm group type: Active Comparator
description: In the control arm of Phase 2b, patients will receive platinum-based chemotherapy until disease progression or unacceptable toxicity.
intervention type: Biological
intervention name: quaratusugene ozeplasmid
description: 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.
arm group label: Investigational
other name: Reqorsa
intervention type: Drug
intervention name: osimertinib
description: 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.
arm group label: Investigational
other name: Tagrisso
intervention type: Drug
intervention name: Platinum-Based Chemotherapy
description: Cisplatin and carboplatin are intravenously administered platinum agents that are combined with other cytotoxic chemotherapy agents such as pemetrexed.
arm group label: Control
other name: cisplatin
other name: carboplatin
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Mark S. Berger, MD
role: Study Director
affiliation: Genprex, Inc.
last name: Sr Director, Clinical Operations
phone: 1-877-774-GNPX
email: kcombs@genprex.com
last name: Chief Medical Officer
phone: 1-877-774-GNPX
email: mberger@genprex.com
facility: 
status: Recruiting
contact: 
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status: Recruiting
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status: Recruiting
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status: Recruiting
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status: Recruiting
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country: United States
responsible party type: Sponsor
mesh term: Carcinoma, Non-Small-Cell Lung
mesh term: Cisplatin
mesh term: Carboplatin
mesh term: Osimertinib
sharing ipd: No