<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/NCT04495153</url>
  </required_header>
  <id_info>
    <org_study_id>LuTK02</org_study_id>
    <nct_id>NCT04495153</nct_id>
  </id_info>
  <brief_title>CAN-2409 Plus Prodrug With Standard of Care Immune Checkpoint Inhibitor for Stage III/IV NSCLC</brief_title>
  <official_title>CAN-2409 Plus Prodrug With Standard of Care Immune Checkpoint Inhibitor for Stage III/IV NSCLC Patients</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Candel Therapeutics, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>NYU Langone Health</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Candel Therapeutics, 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 clinical trial is to evaluate the effects of adding CAN-2409 + prodrug&#xD;
      for stage III/IV NSCLC patients who are on standard of care first line immune checkpoint&#xD;
      inhibitor (ICI) treatment with evidence that the clinical response is inadequate. CAN-2409 is&#xD;
      a viral immunotherapy approach that induces tumor-infiltrating T-cells and a consequent PD-L1&#xD;
      up-regulation. A combination of CAN-2409 added to standard of care (SOC) checkpoint&#xD;
      inhibitors may lead to improved long-term outcomes for patients with NSCLC who have&#xD;
      suboptimal response to ICI therapy.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This clinical trial evaluates the addition of CAN-2409 plus prodrug for stage III/IV NSCLC&#xD;
      patients who are on standard of care first line ICI (anti-PD-1/PD-L1) but with evidence of&#xD;
      suboptimal response (either disease progression or stable disease at time of study&#xD;
      enrollment). CAN-2409 plus prodrug has been shown to increase the response rate to ICI in&#xD;
      animal studies. Safety and tolerability of CAN-2409 plus prodrug has been demonstrated in&#xD;
      clinical trials in over 950 patients with cancer, including cancers of the lung, pancreas,&#xD;
      prostate, and brain. Initial proof of mechanism has been shown in non-small lung cancer,&#xD;
      prostate cancer, high-grade glioma, and pancreatic cancer. The eligibility criterion in the&#xD;
      current clinical trial is based on time on ICI and response status with cohorts as follows:&#xD;
&#xD;
      Cohort 1A and 1B: patients with stable disease radiographically at least 18 weeks after&#xD;
      starting ICI treatment and who are clinically stable&#xD;
&#xD;
      Cohort 2A and 2B: patients with evidence of radiographic progression at least 18 weeks after&#xD;
      starting ICI treatment but who are clinically stable.&#xD;
&#xD;
      Cohort 3, which is now closed for enrollment, was for patients who had evidence of&#xD;
      radiographic progression at least 9 weeks after starting ICI but who were clinically stable.&#xD;
&#xD;
      The specific ICI treatment regimen is not specified to allow for different standard of care&#xD;
      options with or without chemotherapy; for example, pembrolizumab alone, pembrolizumab plus&#xD;
      chemotherapy, or atezolizumab/chemotherapy. In addition, it allows stage III patients after&#xD;
      chemoradiation who may be on durvalumab as their standard of care. For example, a stage III&#xD;
      patient may be eligible for cohort 2 if they have radiographic progression but are clinically&#xD;
      stable 18 weeks after starting durvalumab.&#xD;
&#xD;
      The release of Version 05 of the protocol increased enrollment numbers into Cohorts 1 and 2&#xD;
      (from target n=32 evaluable to n=40 evaluable), while closing Cohort 3. In Amendment 6,&#xD;
      cohort 1B and 2B were initiated to evaluate a 3-dose regimen of CAN-2409 + prodrug.&#xD;
      Adjustments to the sample size extended the anticipated primary completion date for this&#xD;
      trial.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">October 13, 2020</start_date>
  <completion_date type="Anticipated">December 2026</completion_date>
  <primary_completion_date type="Anticipated">December 2024</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <intervention_model_description>The study is a phase II prospective study to evaluate the safety and potential efficacy of CAN-2409 plus prodrug added to standard of care immune checkpoint inhibitor (ICI) therapy in stage III/IV NSCLC</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Response rate</measure>
    <time_frame>12 months</time_frame>
    <description>Tumor response as measured by RECIST criteria including overall response rate (ORR) and/or disease control rate (DCR)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Safety graded by CTCAE version 5.0</measure>
    <time_frame>12 weeks</time_frame>
    <description>Frequency of adverse events</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Biomarker Studies</measure>
    <time_frame>6 months</time_frame>
    <description>Blood and tumor will be evaluated for changes in immune response before and after CAN-2409 + prodrug</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival (OS)</measure>
    <time_frame>3 years</time_frame>
    <description>Defined as time from date of first dose of CAN-2409 to death by any cause (OS-1). An additional OS will be defined as time from ICI treatment initiation to death due to any cause (OS-2).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression Free Survival (PFS)</measure>
    <time_frame>3 years</time_frame>
    <description>Defined as time from date of first dose of CAN-2409 to post-treatment progression or death by any cause (PFS-1). An additional PFS estimate will be calculated from ICI treatment initiation (PFS-2).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in patient-reported symptoms using the NSCLC-SAQ</measure>
    <time_frame>12 months</time_frame>
    <description>Non-small Cell Lung Cancer Symptoms Assessment Questionnaire (NSCLC-SAQ) score after compared to before treatment. The lowest score possible is 0, and the highest score possible is 20. Higher score indicates more severe symptoms.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Response rate</measure>
    <time_frame>12 months</time_frame>
    <description>Tumor Response as measured by iRECIST criteria</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">86</enrollment>
  <condition>Non Small Cell Lung Cancer</condition>
  <arm_group>
    <arm_group_label>Cohorts</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Cohort 1A and 1B - persistent but stable disease at least 18 weeks after starting ICI treatment&#xD;
Cohort 2A and 2B - radiographic progressive disease at least 18 weeks after starting ICI treatment&#xD;
Cohort 3 - refractory disease defined as progressed by imaging at least 9 weeks after starting ICI treatment (CLOSED TO ENROLLMENT)</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Aglatimagene besadenovec</intervention_name>
    <description>Two courses (Cohort 1A and Cohort 2A) or three courses (Cohort 1B and Cohort 2B) of CAN-2409 injection into an accessible involved tumor site followed by 14 days of prodrug (valacyclovir or acyclovir). For Cohort 1B, the third course is optional. All patients will continue standard of care immune checkpoint inhibitor with or without chemotherapy.</description>
    <arm_group_label>Cohorts</arm_group_label>
    <other_name>CAN-2409</other_name>
    <other_name>AdV-tk</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Patients with Stage III/IV NSCLC on first line treatment with anti-PD-1/PD-L1 (ICI)&#xD;
             +/- chemotherapy for their current stage of disease and fits into one of the following&#xD;
             cohorts as determined by investigator, preferably as per RECIST 1.1: Cohort 1) have&#xD;
             persistent but stable disease at least 18 weeks after starting ICI treatment, or&#xD;
             Cohort 2) have radiographic progressive disease at least 18 weeks after starting ICI&#xD;
             treatment&#xD;
&#xD;
          2. RECIST evaluable disease including a lesion that is amenable to injection&#xD;
&#xD;
          3. Able and willing to undergo a pre-treatment and on-treatment biopsies, if feasible&#xD;
&#xD;
          4. ECOG Performance status of 0 or 1&#xD;
&#xD;
          5. 18 years of age or older&#xD;
&#xD;
          6. Granulocyte count (ANC) ≥ 1,000/mm3&#xD;
&#xD;
          7. Hemoglobin ≥ 8 g/dl (patients may be transfused to meet this criterion)&#xD;
&#xD;
          8. Platelets ≥ 75,000/mm3&#xD;
&#xD;
          9. Total bilirubin ≤ 1.5 x upper limit of normal, except for patients with known Gilbert&#xD;
             disease who must have total bilirubin ≤ 3 x upper limit of normal&#xD;
&#xD;
         10. SGOT (AST) ≤ 5x upper limit of normal and if elevated, not clinically significant such&#xD;
             that ICI can continue&#xD;
&#xD;
         11. INR no more than 0.2 above upper limit of normal and aPTT not &gt;1.2 x upper limit of&#xD;
             normal, and value is acceptable for patient to undergo injection procedure. If on&#xD;
             anti-coagulation, it must be clinically acceptable to hold anti-coagulation for the&#xD;
             injection procedures per investigator discretion&#xD;
&#xD;
         12. Serum creatinine &lt; 2mg/dl and calculated creatinine clearance &gt; 30ml/min&#xD;
&#xD;
         13. Clinically stable and able to continue ICI for at least the 12-week treatment period&#xD;
&#xD;
         14. Within 6 months of enrollment, no change of ICI therapy or prior interruptions of more&#xD;
             than 4 weeks of current ICI&#xD;
&#xD;
         15. Patients should not have received focal therapy (e.g., radiotherapy) at more than&#xD;
             three different sites of disease within 12-months prior to enrollment&#xD;
&#xD;
         16. Patients must give study specific informed consent prior to enrollment and any study&#xD;
             specific procedures&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Patients with a history of severe immune related adverse events related to ICI&#xD;
&#xD;
          2. Patients who require ongoing therapy with disease-modifying antirheumatic drugs&#xD;
             (DMARDs), immunomodulators or systemic immunosuppressive drugs including systemic&#xD;
             corticosteroids (&gt;10 mg prednisone per day or equivalent) - premedication for ICI or&#xD;
             chemotherapy is allowed&#xD;
&#xD;
          3. Patients with a history of active autoimmune disease requiring treatment in the past 2&#xD;
             years&#xD;
&#xD;
          4. Patients with uncontrolled intercurrent illness including, but not limited to, ongoing&#xD;
             or active infection, symptomatic congestive heart failure, unstable angina pectoris,&#xD;
             cardiac arrhythmia, active hepatitis, or psychiatric illness/social situations that&#xD;
             would limit compliance with study requirements&#xD;
&#xD;
          5. Women who are pregnant, lactating or intend to become pregnant during the study&#xD;
&#xD;
          6. Patients who are known to be HIV positive&#xD;
&#xD;
          7. Patients with a history of hypersensitivity or allergic reactions to valacyclovir or&#xD;
             acyclovir&#xD;
&#xD;
          8. Patients with significant heart disease (New York Heart Association Functional&#xD;
             Classification III or IV)&#xD;
&#xD;
          9. Patients with continuous oxygen dependence &gt;2L/min at rest&#xD;
&#xD;
         10. Tumor impinging on a neurovascular structure such that inflammation in the site may&#xD;
             put patient at risk of compromise as determined by the investigator&#xD;
&#xD;
         11. Patients with uncontrolled brain metastases as per investigator&#xD;
&#xD;
         12. Patients with liver metastases involving more than half of the liver&#xD;
&#xD;
         13. Patients with known EGFR mutation, ALK fusion, or ROS1 fusion positive NSCLC, or that&#xD;
             are receiving tyrosine kinase inhibitor (TKI) agents/ALK/ROS1 inhibitors&#xD;
&#xD;
         14. Patients with known interstitial lung diseases (ILDs) requiring active therapy&#xD;
             (Radiographic fibrosis not requiring therapy is allowed)&#xD;
&#xD;
         15. Patients receiving vascular endothelial growth factor (VEGF) inhibitors (including&#xD;
             bevacizumab, ramucirumab) within the past 2 months or five half-lives, whichever is&#xD;
             longer&#xD;
&#xD;
         16. Patients must have no concurrent malignancy requiring treatment (except squamous or&#xD;
             basal cell skin cancers)&#xD;
&#xD;
         17. Patients without contrast enhanced imaging at baseline or those with contraindication&#xD;
             to the use of contrast.&#xD;
&#xD;
         18. Patients who are pregnant, breastfeeding, or plan to become pregnant.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Mayo Clinic Hospital</name>
      <address>
        <city>Phoenix</city>
        <state>Arizona</state>
        <zip>85054</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Panayiotis Savvides, MD, PhD</last_name>
      <phone>480-933-6836</phone>
      <email>Savvides.Panayiotis@mayo.edu</email>
    </contact>
    <investigator>
      <last_name>Kenneth Sakata, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>UConn Health</name>
      <address>
        <city>Farmington</city>
        <state>Connecticut</state>
        <zip>06030</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Quratulain (Annie) Ali</last_name>
      <phone>860-679-7648</phone>
      <email>qali@uchc.edu</email>
    </contact>
    <investigator>
      <last_name>Omar Ibrahim, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Yale University, Yale Cancer Center</name>
      <address>
        <city>New Haven</city>
        <state>Connecticut</state>
        <zip>06510</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jessica Whitehurst</last_name>
      <phone>203-836-1029</phone>
      <email>jessica.whitehurst@yale.eduu</email>
    </contact>
    <investigator>
      <last_name>Scott Gettinger, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>University of Chicago</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60637</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Paige Pribble</last_name>
      <phone>773-702-4983</phone>
      <email>Ppribble@bsd.uchicago.edu</email>
    </contact>
    <investigator>
      <last_name>Christine Bestvina, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>University of Maryland, Baltimore</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21201</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Maha Khalil</last_name>
      <phone>410-328-5009</phone>
      <email>mkhalil@umm.edu</email>
    </contact>
    <investigator>
      <last_name>Ranee Mehra, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Mayo Clinic</name>
      <address>
        <city>Rochester</city>
        <state>Minnesota</state>
        <zip>55905</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Travis Fisher</last_name>
      <phone>507-538-1960</phone>
      <email>fisher.travis1@mayo.edu</email>
    </contact>
    <contact_backup>
      <last_name>Karlyn Pierson</last_name>
      <email>Pierson.Karlyn@mayo.edu</email>
    </contact_backup>
    <investigator>
      <last_name>Janani Reisenauer, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>NYU Langone Health</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10016</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>NYU Clinicaltrials.gov Group</last_name>
      <phone>929-455-2453</phone>
      <email>CT.gov@nyulangone.org</email>
    </contact>
    <investigator>
      <last_name>Daniel H. Sterman, MD FCCP, ATSF</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Cleveland Clinic</name>
      <address>
        <city>Cleveland</city>
        <state>Ohio</state>
        <zip>44106</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Withdrawn</status>
  </location>
  <location>
    <facility>
      <name>The Ohio State University Wexner Medical Center</name>
      <address>
        <city>Columbus</city>
        <state>Ohio</state>
        <zip>43210</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Carly Pilcher</last_name>
      <phone>614-685-5414</phone>
      <email>Carly.Pilcher@osumc.edu</email>
    </contact>
    <investigator>
      <last_name>Jasleen Pannu, MBBS</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>University of Pennsylvania</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19104</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Melissa Volpe</last_name>
      <phone>215-220-9703</phone>
      <email>Melissa.Volpe@pennmedicine.upenn.edu</email>
    </contact>
    <investigator>
      <last_name>Charu Aggarwal, MD, MPH</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Vanderbilt University Medical Center</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37232</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Clinical Trials Information Program</last_name>
      <phone>800-811-8480</phone>
      <email>CIP@vumc.org</email>
    </contact>
    <investigator>
      <last_name>Fabien Maldonado, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>The University of Texas MD Anderson Cancer Center</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jhankruti Zaveri</last_name>
      <phone>713-745-2645</phone>
      <email>jzaveri@mdanderson.org</email>
    </contact>
    <investigator>
      <last_name>George Eapen, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>University of Utah</name>
      <address>
        <city>Salt Lake City</city>
        <state>Utah</state>
        <zip>84112</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Kaitlin Stephens</last_name>
      <phone>801-213-8494</phone>
      <email>kaitlin.stephens@hci.utah.edu</email>
    </contact>
    <investigator>
      <last_name>Sonam Puri, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Hunter Holmes McGuire VA Medical Center</name>
      <address>
        <city>Richmond</city>
        <state>Virginia</state>
        <zip>23249</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Krista Chafin</last_name>
      <phone>804-675-5625</phone>
      <email>krista.chafin@va.gov</email>
    </contact>
    <investigator>
      <last_name>Leigh Swartz, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Virginia Commonwealth University</name>
      <address>
        <city>Richmond</city>
        <state>Virginia</state>
        <zip>23298</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Melissa Schaefer</last_name>
      <phone>804-827-1025</phone>
      <email>masseylung@vcu.edu</email>
    </contact>
    <investigator>
      <last_name>Erin Alesi, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2023</verification_date>
  <study_first_submitted>July 24, 2020</study_first_submitted>
  <study_first_submitted_qc>July 30, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 31, 2020</study_first_posted>
  <last_update_submitted>August 30, 2023</last_update_submitted>
  <last_update_submitted_qc>August 30, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 31, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Lung cancer</keyword>
  <keyword>Immunotherapy</keyword>
  <keyword>GMCI</keyword>
  <keyword>AdV-tk</keyword>
  <keyword>aglatimagene besadenovec</keyword>
  <keyword>CAN-2409</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lung Neoplasms</mesh_term>
    <mesh_term>Carcinoma, Non-Small-Cell Lung</mesh_term>
  </condition_browse>
  <!-- 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/NCT04495153
org study id: LuTK02
nct id: NCT04495153
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
The purpose of this clinical trial is to evaluate the effects of adding CAN-2409 + prodrug
      for stage III/IV NSCLC patients who are on standard of care first line immune checkpoint
      inhibitor (ICI) treatment with evidence that the clinical response is inadequate. CAN-2409 is
      a viral immunotherapy approach that induces tumor-infiltrating T-cells and a consequent PD-L1
      up-regulation. A combination of CAN-2409 added to standard of care (SOC) checkpoint
      inhibitors may lead to improved long-term outcomes for patients with NSCLC who have
      suboptimal response to ICI therapy.
This clinical trial evaluates the addition of CAN-2409 plus prodrug for stage III/IV NSCLC
      patients who are on standard of care first line ICI (anti-PD-1/PD-L1) but with evidence of
      suboptimal response (either disease progression or stable disease at time of study
      enrollment). CAN-2409 plus prodrug has been shown to increase the response rate to ICI in
      animal studies. Safety and tolerability of CAN-2409 plus prodrug has been demonstrated in
      clinical trials in over 950 patients with cancer, including cancers of the lung, pancreas,
      prostate, and brain. Initial proof of mechanism has been shown in non-small lung cancer,
      prostate cancer, high-grade glioma, and pancreatic cancer. The eligibility criterion in the
      current clinical trial is based on time on ICI and response status with cohorts as follows:

      Cohort 1A and 1B: patients with stable disease radiographically at least 18 weeks after
      starting ICI treatment and who are clinically stable

      Cohort 2A and 2B: patients with evidence of radiographic progression at least 18 weeks after
      starting ICI treatment but who are clinically stable.

      Cohort 3, which is now closed for enrollment, was for patients who had evidence of
      radiographic progression at least 9 weeks after starting ICI but who were clinically stable.

      The specific ICI treatment regimen is not specified to allow for different standard of care
      options with or without chemotherapy; for example, pembrolizumab alone, pembrolizumab plus
      chemotherapy, or atezolizumab/chemotherapy. In addition, it allows stage III patients after
      chemoradiation who may be on durvalumab as their standard of care. For example, a stage III
      patient may be eligible for cohort 2 if they have radiographic progression but are clinically
      stable 18 weeks after starting durvalumab.

      The release of Version 05 of the protocol increased enrollment numbers into Cohorts 1 and 2
      (from target n=32 evaluable to n=40 evaluable), while closing Cohort 3. In Amendment 6,
      cohort 1B and 2B were initiated to evaluate a 3-dose regimen of CAN-2409 + prodrug.
      Adjustments to the sample size extended the anticipated primary completion date for this
      trial.
allocation: N/A
intervention model: Single Group Assignment
intervention model description: The study is a phase II prospective study to evaluate the safety and potential efficacy of CAN-2409 plus prodrug added to standard of care immune checkpoint inhibitor (ICI) therapy in stage III/IV NSCLC
primary purpose: Treatment
masking: None (Open Label)
measure: Response rate
time frame: 12 months
description: Tumor response as measured by RECIST criteria including overall response rate (ORR) and/or disease control rate (DCR)
measure: Safety graded by CTCAE version 5.0
time frame: 12 weeks
description: Frequency of adverse events
measure: Biomarker Studies
time frame: 6 months
description: Blood and tumor will be evaluated for changes in immune response before and after CAN-2409 + prodrug
measure: Overall Survival (OS)
time frame: 3 years
description: Defined as time from date of first dose of CAN-2409 to death by any cause (OS-1). An additional OS will be defined as time from ICI treatment initiation to death due to any cause (OS-2).
measure: Progression Free Survival (PFS)
time frame: 3 years
description: Defined as time from date of first dose of CAN-2409 to post-treatment progression or death by any cause (PFS-1). An additional PFS estimate will be calculated from ICI treatment initiation (PFS-2).
measure: Changes in patient-reported symptoms using the NSCLC-SAQ
time frame: 12 months
description: Non-small Cell Lung Cancer Symptoms Assessment Questionnaire (NSCLC-SAQ) score after compared to before treatment. The lowest score possible is 0, and the highest score possible is 20. Higher score indicates more severe symptoms.
measure: Response rate
time frame: 12 months
description: Tumor Response as measured by iRECIST criteria
arm group label: Cohorts
arm group type: Other
description: Cohort 1A and 1B - persistent but stable disease at least 18 weeks after starting ICI treatment
Cohort 2A and 2B - radiographic progressive disease at least 18 weeks after starting ICI treatment
Cohort 3 - refractory disease defined as progressed by imaging at least 9 weeks after starting ICI treatment (CLOSED TO ENROLLMENT)
intervention type: Biological
intervention name: Aglatimagene besadenovec
description: Two courses (Cohort 1A and Cohort 2A) or three courses (Cohort 1B and Cohort 2B) of CAN-2409 injection into an accessible involved tumor site followed by 14 days of prodrug (valacyclovir or acyclovir). For Cohort 1B, the third course is optional. All patients will continue standard of care immune checkpoint inhibitor with or without chemotherapy.
arm group label: Cohorts
other name: CAN-2409
other name: AdV-tk
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Withdrawn
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
country: United States
responsible party type: Sponsor
mesh term: Lung Neoplasms
mesh term: Carcinoma, Non-Small-Cell Lung