<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/NCT04491084</url>
  </required_header>
  <id_info>
    <org_study_id>2020-11868</org_study_id>
    <nct_id>NCT04491084</nct_id>
  </id_info>
  <brief_title>FLT3 Ligand, CD40 Agonist Antibody, and Stereotactic Radiotherapy</brief_title>
  <acronym>FLT3</acronym>
  <official_title>FLT3 Ligand (CDX-301), CD40 Agonist Antibody (CDX-1140), and Stereotactic Radiotherapy Versus Standard Therapy for Advanced Non-small Cell Lung Cancer: A Phase I/II Randomized Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Albert Einstein College of Medicine</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Celldex Therapeutics</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Albert Einstein College of Medicine</source>
  <oversight_info>
    <has_dmc>Yes</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 study is to test a new way of treating the most common form of lung&#xD;
      cancer. The investigators are testing a combination of radiotherapy with two new forms of&#xD;
      immunotherapy. This study is testing the safety and effectiveness of this treatment approach&#xD;
      as compared to standard treatment options.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a randomized, open-label phase I/II study. Subjects will be randomized in a 1:1 ratio&#xD;
      to receive FLT3 ligand (CDX-301), anti-CD40 antibody (CDX-1140) and SBRT (Arm 1) versus&#xD;
      standard care (Arm 2). Subjects on either study arm with limited disease will receive SBRT to&#xD;
      all evident sites of active disease. Subjects on Arm 1 with extensive disease will initially&#xD;
      receive SBRT to a single site of disease but may receive additional &quot;cycles&quot; of FLT3 ligand&#xD;
      (CDX-301) anti-CD40 antibody (CDX-1140), and SBRT at later time points. Subjects on Arm 2&#xD;
      with extensive disease are expected to receive some form of standard systemic therapy (e.g.,&#xD;
      docetaxel). Subjects on Arm 2 with limited disease may also receive standard systemic therapy&#xD;
      following completion of SBRT to all sites of evident disease, at the discretion of the&#xD;
      treating physicians. All subjects will be followed closely for treatment-related toxicities.&#xD;
      Whole-body PET/CT and CT imaging will be performed prior to study entry, and restaging CT&#xD;
      will be performed every 8 weeks thereafter.&#xD;
&#xD;
      In the phase I component of this study, subjects will be randomized between study arms until&#xD;
      6 subjects have been randomized to Arm 1. Study accrual will then be halted until 8 weeks&#xD;
      after the last study subject begins treatment.&#xD;
&#xD;
      If the pre-specified safety criteria are achieved in the Phase I portion of this study, the&#xD;
      study will proceed to phase II. The total sample size (Phase I and Phase II) will be 46&#xD;
      subjects. All 46 subjects will be included in efficacy analyses.&#xD;
&#xD;
      If the pre-specified safety criteria are not achieved in the Phase I portion of this study,&#xD;
      the investigators and Celldex will review safety data from this trial as well as other trials&#xD;
      using CDX-301 and CDX-1140 and determine if the experimental treatment regimen should be&#xD;
      altered (e.g., by reducing the CDX-1140 dose). The study protocol would be amended&#xD;
      accordingly, and Phase I component with the new treatment regimen would be added.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Low accrual&#xD;
  </why_stopped>
  <start_date type="Actual">January 1, 2021</start_date>
  <completion_date type="Actual">August 18, 2022</completion_date>
  <primary_completion_date type="Actual">August 18, 2022</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>Parallel Assignment</intervention_model>
    <intervention_model_description>This is a randomized, open-label phase I/II study. Subjects will be randomized in a 1:1 ratio to receive FLT3 ligand (CDX-301), anti-CD40 antibody (CDX-1140) and SBRT (Arm 1) versus standard care (Arm 2).</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Phase I: Dose-limiting Toxicity (DLT), Defined as Follows:</measure>
    <time_frame>up to 8 weeks after initiation of study therapy</time_frame>
    <description>Death&#xD;
Any ≥ Grade 3 non-hematological toxicity, with the following exceptions:&#xD;
Grade 3 alopecia, vitiligo, or endocrinopathies controlled by hormone replacement therapy Grade 3 nausea that resolves to ≤ grade 2 with or without treatment within 72 hours Grade 3 vomiting and diarrhea that resolves to ≤ grade 2 with or without treatment within 72 hours Grade 3 fatigue that resolves to ≤ grade 2 within 5 days Grade 3 hypertension in the absence of maximal medical therapy Grade 3 adverse event of tumor flare (defined as local pain, irritation, or rash localized at sites of known or suspected tumor) of ≤ 7 days in duration Grade 3 amylase or lipase abnormalities that are not associated with symptoms or clinical manifestations of pancreatitis. It is recommended to consult with the Principal Investigator for grade 4 amylase or lipase abnormalities&#xD;
Grade 3 clinically significant laboratory abnormalities that are asymptomatic and can be reversed within 72 hours, however:&#xD;
Any Grade 4</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Phase II: Progression-free Survival (PFS) Duration</measure>
    <time_frame>defined as time from study registration until disease progression (scored using iRECIST) or death, whichever comes first up to 51 weeks.</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Overall Survival (OS) Duration</measure>
    <time_frame>From date of registration until the date of death from any cause, assessed up to 2 years</time_frame>
    <description>Length of time that patient survives from time of study registration</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Radiographic Responses Using Descriptive Statistics</measure>
    <time_frame>From date of registration, assessed up to 4 months</time_frame>
    <description>The clinical benefit rate (CBR) will be defined as the percentage of subjects who achieve best response of confirmed CR or PR, or stable disease (SD) for at least four months.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of Life Using EORTC QLQ-LC13 (Quality of Life Questionnaire, Lung Cancer)</measure>
    <time_frame>1 year</time_frame>
    <description>Summary statistics (mean, standard deviation, median, 25th and 75th percentiles, and range) and the mean change from baseline of linear-transformed scores will be reported for all the items and subscales of the EORTC QLQ-C30 questionnaire and the QLQ-LC13, according to the EORTC scoring manual guidelines. higher scores are a better level of functioning</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of Life Using QLQ-C30 (Quality of Life Questionnaire)</measure>
    <time_frame>1 year</time_frame>
    <description>Summary statistics (mean, standard deviation, median, 25th and 75th percentiles, and range) and the mean change from baseline of linear-transformed scores will be reported for all the items and subscales of the EORTC QLQ-C30 questionnaire and the QLQ-LC13, according to the EORTC scoring manual guidelines. Most items are scored 1 to 4, higher scores are a better level of functioning.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Daily Step Count Using Descriptive Statistics</measure>
    <time_frame>1 year</time_frame>
    <description>Average daily step counts</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">5</enrollment>
  <condition>Non Small Cell Lung Cancer</condition>
  <condition>Lung Cancer</condition>
  <arm_group>
    <arm_group_label>FLT3 ligand (CDX-301), anti-CD40 antibody (CDX-1140), and SBRT</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects on either study arm with limited disease will receive SBRT to all evident sites of active disease. Subjects on Arm 1 with extensive disease will initially receive SBRT to a single site of disease but may receive additional &quot;cycles&quot; of FLT3 ligand, anti-CD40 antibody, and SBRT at later time points.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Standard care</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Subjects on either study arm with limited disease will receive SBRT to all evident sites of active disease.Subjects on Arm 2 with extensive disease are expected to receive some form of standard systemic therapy (e.g., docetaxel). Subjects on Arm 2 with limited disease may also receive standard systemic therapy following completion of SBRT to all sites of evident disease, at the discretion of the treating physicians.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>FLT3 Ligand (CDX-301)</intervention_name>
    <description>Fms-like tyrosine kinase 3 (FLT3) ligand is a potent hematopoietic growth factor that mobilizes stem cells and greatly increases the number of circulating dendritic cells (DCs) in blood and organs.</description>
    <arm_group_label>FLT3 ligand (CDX-301), anti-CD40 antibody (CDX-1140), and SBRT</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>anti-CD40 antibody (CDX-1140)</intervention_name>
    <description>CD40 is a key molecule in the regulation of immune responses whose activity can be modulated using antibodies. CD40 is a tumor necrosis factor receptor superfamily member expressed on antigen presenting cells, including dendritic cells, as well as a host of other cell types, including a wide range of tumor cells</description>
    <arm_group_label>FLT3 ligand (CDX-301), anti-CD40 antibody (CDX-1140), and SBRT</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>SBRT</intervention_name>
    <description>For subjects on Arm 1, SBRT will be delivered concurrently with FLT3 ligand during Week 1 of study therapy. If only one lesion is being treated, SBRT should be completed during week 1 (e.g., with daily treatments for a 5-fraction course of treatments every other day for a 3-fraction course). In cases where multiple lesions are being treated with SBRT (Arm 1 or Arm 2) or if treatment is interrupted due to technical issues or intercurrent illness, SBRT may extend beyond Week 1.</description>
    <arm_group_label>FLT3 ligand (CDX-301), anti-CD40 antibody (CDX-1140), and SBRT</arm_group_label>
    <arm_group_label>Standard care</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Histologically proven NSCLC, not classically deemed to be amenable to curative therapy&#xD;
             based on disease extent at the time of diagnosis or disease progression after the&#xD;
             initial diagnosis&#xD;
&#xD;
          -  Age ≥ 18 years&#xD;
&#xD;
          -  Prior treatment with at least two lines of systemic therapy for advanced NSCLC,&#xD;
             including one line of platinum-based combination chemotherapy&#xD;
&#xD;
          -  Treatment with concurrent chemotherapy and immunotherapy can count as two lines of&#xD;
             therapy for the purposes of study eligibility.&#xD;
&#xD;
          -  Radiological assessment within 21 days prior to study entry demonstrating measurable&#xD;
             disease that includes at least one pulmonary or extrapulmonary lesion ≥ 1 cm in&#xD;
             greatest dimension that would be amenable to SBRT and at least one measurable lesion&#xD;
             that would be outside of the SBRT treatment fields&#xD;
&#xD;
          -  ECOG performance status 0-2&#xD;
&#xD;
          -  Both men and women enrolled in this trial must agree to use adequate birth control&#xD;
             measures during the trial and for at least 90 days after last receipt of study&#xD;
             therapy. Patients and/or partners who are surgically sterile or postmenopausal are&#xD;
             exempt from this requirement.&#xD;
&#xD;
          -  The following laboratory results, within 21 days prior to first study drug&#xD;
             administration (Arm 1) or within 21 days prior to study registration (Arm 2):&#xD;
&#xD;
        Hemoglobin ≥ 9.0 g/dL Absolute neutrophil count ≥ 1.5 x 109/L Platelet count ≥ 100 x 109/L&#xD;
        Serum creatinine ≤ 1.5 x ULN OR creatinine clearance (by Cockcroft-Gault formula) &gt; 60&#xD;
        mL/min AST and ALT ≤ 2.5 x ULN Total bilirubin ≤ 2.0 x ULN (except patients with Gilbert's&#xD;
        syndrome, who must have a total bilirubin ≤ 3.0 mg/dL)&#xD;
&#xD;
        -Negative SARS-CoV-2 (COVID-19) PCR test. COVID-19 testing may be repeated periodically&#xD;
        based on institutional policies and must be repeated for any subject with unexplained signs&#xD;
        (e.g., imaging findings, fever) or symptoms (e.g., anosmia) concerning for COVID-19&#xD;
        infection or with recent known exposure to COVID-19.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Prior therapy with any anti-CD40 antibody or FLT3 ligand&#xD;
&#xD;
          -  Less than 21 days between registration and the last receipt of chemotherapy, targeted&#xD;
             cancer therapy, immunotherapy, radiotherapy (excluding palliative radiotherapy), or&#xD;
             major surgery.&#xD;
&#xD;
          -  Untreated central nervous system metastases. Patients with a history of brain&#xD;
             metastases must have had no CNS-directed therapy within the past 60 days and&#xD;
             radiological assessment within 30 days of study entry demonstrating a lack of&#xD;
             progressive CNS disease. -Patients without a history of brain metastases and without&#xD;
             symptoms suggestive of brain metastasis do not require staging imaging of the brain&#xD;
             prior to study enrollment.&#xD;
&#xD;
          -  Known mutation/amplification in FLT3&#xD;
&#xD;
          -  Ongoing or recent (within 21 days prior to study entry) use of high dose oral&#xD;
             corticosteroids (≥ 2 mg of dexamethasone daily or equivalent) or inhaled&#xD;
             corticosteroids. Intranasal and/or intraarticular corticosteroid use is permitted.&#xD;
&#xD;
          -  History of non-infectious pneumonitis or any ongoing pneumonitis&#xD;
&#xD;
          -  History of allogeneic organ transplant or active autoimmune disease&#xD;
&#xD;
          -  Other active malignancy for which systemic therapy (excluding hormonal therapy for&#xD;
             breast or prostate cancer) is indicated.&#xD;
&#xD;
          -  History of myocardial infarction, cerebral vascular accident, thrombosis, or pulmonary&#xD;
             embolus within 12 months prior to study registration.&#xD;
&#xD;
          -  Uncontrolled intercurrent illness including, but not limited to, symptomatic&#xD;
             congestive heart failure, unstable angina pectoris, uncontrolled cardiac arrhythmia,&#xD;
             or psychiatric illness/social situation that would limit compliance with study&#xD;
             requirements as judged by the treating physicians&#xD;
&#xD;
          -  Active infection requiring systemic therapy, known HIV infection, or positive test for&#xD;
             hepatitis B surface antigen or hepatitis C (antibody screen and if positive confirmed&#xD;
             by RNA analysis). If positive results are not indicative of a true active or chronic&#xD;
             infection, the patient can be enrolled after discussion with, and agreement by, the&#xD;
             Principal Investigator.&#xD;
&#xD;
          -  Receipt of a live vaccine within 30 days prior to the first dose of study drug.&#xD;
             Examples of live vaccines include, but are not limited to, the following: measles,&#xD;
             mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus&#xD;
             Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection&#xD;
             are generally killed virus vaccines and are allowed; however, intranasal influenza&#xD;
             vaccines (e.g., FluMist®) are live attenuated vaccines and are not allowed.&#xD;
&#xD;
          -  Subjects who are not ambulatory or ambulate using a walker are not eligible for the&#xD;
             objective activity monitoring component of this study.&#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>Albert Einstein College of Medicine</name>
      <address>
        <city>Bronx</city>
        <state>New York</state>
        <zip>10461</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>June 2023</verification_date>
  <study_first_submitted>July 21, 2020</study_first_submitted>
  <study_first_submitted_qc>July 28, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 29, 2020</study_first_posted>
  <results_first_submitted>June 23, 2023</results_first_submitted>
  <results_first_submitted_qc>June 23, 2023</results_first_submitted_qc>
  <results_first_posted type="Actual">July 17, 2023</results_first_posted>
  <last_update_submitted>June 23, 2023</last_update_submitted>
  <last_update_submitted_qc>June 23, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">July 17, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Albert Einstein College of Medicine</investigator_affiliation>
    <investigator_full_name>Nitin Ohri</investigator_full_name>
    <investigator_title>Associate Professor</investigator_title>
  </responsible_party>
  <keyword>CDX-301</keyword>
  <keyword>CDX-1140</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>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Antibodies</mesh_term>
    <mesh_term>Flt3 ligand protein</mesh_term>
  </intervention_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>May 26, 2021</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/84/NCT04491084/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>FLT3 Ligand (CDX-301), Anti-CD40 Antibody (CDX-1140), and SBRT</title>
          <description>Subjects on either study arm with limited disease will receive SBRT to all evident sites of active disease. Subjects on Arm 1 with extensive disease will initially receive SBRT to a single site of disease but may receive additional &quot;cycles&quot; of FLT3 ligand, anti-CD40 antibody, and SBRT at later time points.&#xD;
FLT3 Ligand (CDX-301): Fms-like tyrosine kinase 3 (FLT3) ligand is a potent hematopoietic growth factor that mobilizes stem cells and greatly increases the number of circulating dendritic cells (DCs) in blood and organs.&#xD;
anti-CD40 antibody (CDX-1140): CD40 is a key molecule in the regulation of immune responses whose activity can be modulated using antibodies. CD40 is a tumor necrosis factor receptor superfamily member expressed on antigen presenting cells, including dendritic cells, as well as a host of other cell types, including a wide range of tumor cells&#xD;
SBRT: For subjects on Arm 1, SBRT will be delivered concurrently with FLT3 ligand during Week 1 of study therapy. If only one lesion is being treated, SBRT should be completed during week 1 (e.g., with daily treatments for a 5-fraction course of treatments every other day for a 3-fraction course). In cases where multiple lesions are being treated with SBRT (Arm 1 or Arm 2) or if treatment is interrupted due to technical issues or intercurrent illness, SBRT may extend beyond Week 1.</description>
        </group>
        <group group_id="P2">
          <title>Standard Care</title>
          <description>Subjects on either study arm with limited disease will receive SBRT to all evident sites of active disease.Subjects on Arm 2 with extensive disease are expected to receive some form of standard systemic therapy (e.g., docetaxel). Subjects on Arm 2 with limited disease may also receive standard systemic therapy following completion of SBRT to all sites of evident disease, at the discretion of the treating physicians.&#xD;
SBRT: For subjects on Arm 1, SBRT will be delivered concurrently with FLT3 ligand during Week 1 of study therapy. If only one lesion is being treated, SBRT should be completed during week 1 (e.g., with daily treatments for a 5-fraction course of treatments every other day for a 3-fraction course). In cases where multiple lesions are being treated with SBRT (Arm 1 or Arm 2) or if treatment is interrupted due to technical issues or intercurrent illness, SBRT may extend beyond Week 1.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="3"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="3"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>FLT3 Ligand (CDX-301), Anti-CD40 Antibody (CDX-1140), and SBRT</title>
          <description>Subjects on either study arm with limited disease will receive SBRT to all evident sites of active disease. Subjects on Arm 1 with extensive disease will initially receive SBRT to a single site of disease but may receive additional &quot;cycles&quot; of FLT3 ligand, anti-CD40 antibody, and SBRT at later time points.&#xD;
FLT3 Ligand (CDX-301): Fms-like tyrosine kinase 3 (FLT3) ligand is a potent hematopoietic growth factor that mobilizes stem cells and greatly increases the number of circulating dendritic cells (DCs) in blood and organs.&#xD;
anti-CD40 antibody (CDX-1140): CD40 is a key molecule in the regulation of immune responses whose activity can be modulated using antibodies. CD40 is a tumor necrosis factor receptor superfamily member expressed on antigen presenting cells, including dendritic cells, as well as a host of other cell types, including a wide range of tumor cells&#xD;
SBRT: For subjects on Arm 1, SBRT will be delivered concurrently with FLT3 ligand during Week 1 of study therapy. If only one lesion is being treated, SBRT should be completed during week 1 (e.g., with daily treatments for a 5-fraction course of treatments every other day for a 3-fraction course). In cases where multiple lesions are being treated with SBRT (Arm 1 or Arm 2) or if treatment is interrupted due to technical issues or intercurrent illness, SBRT may extend beyond Week 1.</description>
        </group>
        <group group_id="B2">
          <title>Standard Care</title>
          <description>Subjects on either study arm with limited disease will receive SBRT to all evident sites of active disease.Subjects on Arm 2 with extensive disease are expected to receive some form of standard systemic therapy (e.g., docetaxel). Subjects on Arm 2 with limited disease may also receive standard systemic therapy following completion of SBRT to all sites of evident disease, at the discretion of the treating physicians.&#xD;
SBRT: For subjects on Arm 1, SBRT will be delivered concurrently with FLT3 ligand during Week 1 of study therapy. If only one lesion is being treated, SBRT should be completed during week 1 (e.g., with daily treatments for a 5-fraction course of treatments every other day for a 3-fraction course). In cases where multiple lesions are being treated with SBRT (Arm 1 or Arm 2) or if treatment is interrupted due to technical issues or intercurrent illness, SBRT may extend beyond Week 1.</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="2"/>
            <count group_id="B2" value="3"/>
            <count group_id="B3" value="5"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>White</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Spanish/Hispanic/Latino</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Other</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Phase I: Dose-limiting Toxicity (DLT), Defined as Follows:</title>
        <description>Death&#xD;
Any ≥ Grade 3 non-hematological toxicity, with the following exceptions:&#xD;
Grade 3 alopecia, vitiligo, or endocrinopathies controlled by hormone replacement therapy Grade 3 nausea that resolves to ≤ grade 2 with or without treatment within 72 hours Grade 3 vomiting and diarrhea that resolves to ≤ grade 2 with or without treatment within 72 hours Grade 3 fatigue that resolves to ≤ grade 2 within 5 days Grade 3 hypertension in the absence of maximal medical therapy Grade 3 adverse event of tumor flare (defined as local pain, irritation, or rash localized at sites of known or suspected tumor) of ≤ 7 days in duration Grade 3 amylase or lipase abnormalities that are not associated with symptoms or clinical manifestations of pancreatitis. It is recommended to consult with the Principal Investigator for grade 4 amylase or lipase abnormalities&#xD;
Grade 3 clinically significant laboratory abnormalities that are asymptomatic and can be reversed within 72 hours, however:&#xD;
Any Grade 4</description>
        <time_frame>up to 8 weeks after initiation of study therapy</time_frame>
        <population>Data was not collected/aggregated. No analyses conducted.</population>
        <group_list>
          <group group_id="O1">
            <title>FLT3 Ligand (CDX-301), Anti-CD40 Antibody (CDX-1140), and SBRT</title>
            <description>Subjects on either study arm with limited disease will receive SBRT to all evident sites of active disease. Subjects on Arm 1 with extensive disease will initially receive SBRT to a single site of disease but may receive additional &quot;cycles&quot; of FLT3 ligand, anti-CD40 antibody, and SBRT at later time points.&#xD;
FLT3 Ligand (CDX-301): Fms-like tyrosine kinase 3 (FLT3) ligand is a potent hematopoietic growth factor that mobilizes stem cells and greatly increases the number of circulating dendritic cells (DCs) in blood and organs.&#xD;
anti-CD40 antibody (CDX-1140): CD40 is a key molecule in the regulation of immune responses whose activity can be modulated using antibodies. CD40 is a tumor necrosis factor receptor superfamily member expressed on antigen presenting cells, including dendritic cells, as well as a host of other cell types, including a wide range of tumor cells&#xD;
SBRT: For subjects on Arm 1, SBRT will be delivered concurrently with FLT3 ligand during Week 1 of study therapy. If only one lesion is being treated, SBRT should be completed during week 1 (e.g., with daily treatments for a 5-fraction course of treatments every other day for a 3-fraction course). In cases where multiple lesions are being treated with SBRT (Arm 1 or Arm 2) or if treatment is interrupted due to technical issues or intercurrent illness, SBRT may extend beyond Week 1.</description>
          </group>
          <group group_id="O2">
            <title>Standard Care</title>
            <description>Subjects on either study arm with limited disease will receive SBRT to all evident sites of active disease.Subjects on Arm 2 with extensive disease are expected to receive some form of standard systemic therapy (e.g., docetaxel). Subjects on Arm 2 with limited disease may also receive standard systemic therapy following completion of SBRT to all sites of evident disease, at the discretion of the treating physicians.&#xD;
SBRT: For subjects on Arm 1, SBRT will be delivered concurrently with FLT3 ligand during Week 1 of study therapy. If only one lesion is being treated, SBRT should be completed during week 1 (e.g., with daily treatments for a 5-fraction course of treatments every other day for a 3-fraction course). In cases where multiple lesions are being treated with SBRT (Arm 1 or Arm 2) or if treatment is interrupted due to technical issues or intercurrent illness, SBRT may extend beyond Week 1.</description>
          </group>
        </group_list>
        <measure>
          <title>Phase I: Dose-limiting Toxicity (DLT), Defined as Follows:</title>
          <description>Death&#xD;
Any ≥ Grade 3 non-hematological toxicity, with the following exceptions:&#xD;
Grade 3 alopecia, vitiligo, or endocrinopathies controlled by hormone replacement therapy Grade 3 nausea that resolves to ≤ grade 2 with or without treatment within 72 hours Grade 3 vomiting and diarrhea that resolves to ≤ grade 2 with or without treatment within 72 hours Grade 3 fatigue that resolves to ≤ grade 2 within 5 days Grade 3 hypertension in the absence of maximal medical therapy Grade 3 adverse event of tumor flare (defined as local pain, irritation, or rash localized at sites of known or suspected tumor) of ≤ 7 days in duration Grade 3 amylase or lipase abnormalities that are not associated with symptoms or clinical manifestations of pancreatitis. It is recommended to consult with the Principal Investigator for grade 4 amylase or lipase abnormalities&#xD;
Grade 3 clinically significant laboratory abnormalities that are asymptomatic and can be reversed within 72 hours, however:&#xD;
Any Grade 4</description>
          <population>Data was not collected/aggregated. No analyses conducted.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Phase II: Progression-free Survival (PFS) Duration</title>
        <time_frame>defined as time from study registration until disease progression (scored using iRECIST) or death, whichever comes first up to 51 weeks.</time_frame>
        <population>Data was not collected/aggregated. No analyses conducted.</population>
        <group_list>
          <group group_id="O1">
            <title>FLT3 Ligand (CDX-301), Anti-CD40 Antibody (CDX-1140), and SBRT</title>
            <description>Subjects on either study arm with limited disease will receive SBRT to all evident sites of active disease. Subjects on Arm 1 with extensive disease will initially receive SBRT to a single site of disease but may receive additional &quot;cycles&quot; of FLT3 ligand, anti-CD40 antibody, and SBRT at later time points.&#xD;
FLT3 Ligand (CDX-301): Fms-like tyrosine kinase 3 (FLT3) ligand is a potent hematopoietic growth factor that mobilizes stem cells and greatly increases the number of circulating dendritic cells (DCs) in blood and organs.&#xD;
anti-CD40 antibody (CDX-1140): CD40 is a key molecule in the regulation of immune responses whose activity can be modulated using antibodies. CD40 is a tumor necrosis factor receptor superfamily member expressed on antigen presenting cells, including dendritic cells, as well as a host of other cell types, including a wide range of tumor cells&#xD;
SBRT: For subjects on Arm 1, SBRT will be delivered concurrently with FLT3 ligand during Week 1 of study therapy. If only one lesion is being treated, SBRT should be completed during week 1 (e.g., with daily treatments for a 5-fraction course of treatments every other day for a 3-fraction course). In cases where multiple lesions are being treated with SBRT (Arm 1 or Arm 2) or if treatment is interrupted due to technical issues or intercurrent illness, SBRT may extend beyond Week 1.</description>
          </group>
          <group group_id="O2">
            <title>Standard Care</title>
            <description>Subjects on either study arm with limited disease will receive SBRT to all evident sites of active disease.Subjects on Arm 2 with extensive disease are expected to receive some form of standard systemic therapy (e.g., docetaxel). Subjects on Arm 2 with limited disease may also receive standard systemic therapy following completion of SBRT to all sites of evident disease, at the discretion of the treating physicians.&#xD;
SBRT: For subjects on Arm 1, SBRT will be delivered concurrently with FLT3 ligand during Week 1 of study therapy. If only one lesion is being treated, SBRT should be completed during week 1 (e.g., with daily treatments for a 5-fraction course of treatments every other day for a 3-fraction course). In cases where multiple lesions are being treated with SBRT (Arm 1 or Arm 2) or if treatment is interrupted due to technical issues or intercurrent illness, SBRT may extend beyond Week 1.</description>
          </group>
        </group_list>
        <measure>
          <title>Phase II: Progression-free Survival (PFS) Duration</title>
          <population>Data was not collected/aggregated. No analyses conducted.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Overall Survival (OS) Duration</title>
        <description>Length of time that patient survives from time of study registration</description>
        <time_frame>From date of registration until the date of death from any cause, assessed up to 2 years</time_frame>
        <population>Data was not collected/aggregated. No analyses conducted.</population>
        <group_list>
          <group group_id="O1">
            <title>FLT3 Ligand (CDX-301), Anti-CD40 Antibody (CDX-1140), and SBRT</title>
            <description>Subjects on either study arm with limited disease will receive SBRT to all evident sites of active disease. Subjects on Arm 1 with extensive disease will initially receive SBRT to a single site of disease but may receive additional &quot;cycles&quot; of FLT3 ligand, anti-CD40 antibody, and SBRT at later time points.&#xD;
FLT3 Ligand (CDX-301): Fms-like tyrosine kinase 3 (FLT3) ligand is a potent hematopoietic growth factor that mobilizes stem cells and greatly increases the number of circulating dendritic cells (DCs) in blood and organs.&#xD;
anti-CD40 antibody (CDX-1140): CD40 is a key molecule in the regulation of immune responses whose activity can be modulated using antibodies. CD40 is a tumor necrosis factor receptor superfamily member expressed on antigen presenting cells, including dendritic cells, as well as a host of other cell types, including a wide range of tumor cells&#xD;
SBRT: For subjects on Arm 1, SBRT will be delivered concurrently with FLT3 ligand during Week 1 of study therapy. If only one lesion is being treated, SBRT should be completed during week 1 (e.g., with daily treatments for a 5-fraction course of treatments every other day for a 3-fraction course). In cases where multiple lesions are being treated with SBRT (Arm 1 or Arm 2) or if treatment is interrupted due to technical issues or intercurrent illness, SBRT may extend beyond Week 1.</description>
          </group>
          <group group_id="O2">
            <title>Standard Care</title>
            <description>Subjects on either study arm with limited disease will receive SBRT to all evident sites of active disease.Subjects on Arm 2 with extensive disease are expected to receive some form of standard systemic therapy (e.g., docetaxel). Subjects on Arm 2 with limited disease may also receive standard systemic therapy following completion of SBRT to all sites of evident disease, at the discretion of the treating physicians.&#xD;
SBRT: For subjects on Arm 1, SBRT will be delivered concurrently with FLT3 ligand during Week 1 of study therapy. If only one lesion is being treated, SBRT should be completed during week 1 (e.g., with daily treatments for a 5-fraction course of treatments every other day for a 3-fraction course). In cases where multiple lesions are being treated with SBRT (Arm 1 or Arm 2) or if treatment is interrupted due to technical issues or intercurrent illness, SBRT may extend beyond Week 1.</description>
          </group>
        </group_list>
        <measure>
          <title>Overall Survival (OS) Duration</title>
          <description>Length of time that patient survives from time of study registration</description>
          <population>Data was not collected/aggregated. No analyses conducted.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Radiographic Responses Using Descriptive Statistics</title>
        <description>The clinical benefit rate (CBR) will be defined as the percentage of subjects who achieve best response of confirmed CR or PR, or stable disease (SD) for at least four months.</description>
        <time_frame>From date of registration, assessed up to 4 months</time_frame>
        <population>Data was not collected/aggregated. No analyses conducted.</population>
        <group_list>
          <group group_id="O1">
            <title>FLT3 Ligand (CDX-301), Anti-CD40 Antibody (CDX-1140), and SBRT</title>
            <description>Subjects on either study arm with limited disease will receive SBRT to all evident sites of active disease. Subjects on Arm 1 with extensive disease will initially receive SBRT to a single site of disease but may receive additional &quot;cycles&quot; of FLT3 ligand, anti-CD40 antibody, and SBRT at later time points.&#xD;
FLT3 Ligand (CDX-301): Fms-like tyrosine kinase 3 (FLT3) ligand is a potent hematopoietic growth factor that mobilizes stem cells and greatly increases the number of circulating dendritic cells (DCs) in blood and organs.&#xD;
anti-CD40 antibody (CDX-1140): CD40 is a key molecule in the regulation of immune responses whose activity can be modulated using antibodies. CD40 is a tumor necrosis factor receptor superfamily member expressed on antigen presenting cells, including dendritic cells, as well as a host of other cell types, including a wide range of tumor cells&#xD;
SBRT: For subjects on Arm 1, SBRT will be delivered concurrently with FLT3 ligand during Week 1 of study therapy. If only one lesion is being treated, SBRT should be completed during week 1 (e.g., with daily treatments for a 5-fraction course of treatments every other day for a 3-fraction course). In cases where multiple lesions are being treated with SBRT (Arm 1 or Arm 2) or if treatment is interrupted due to technical issues or intercurrent illness, SBRT may extend beyond Week 1.</description>
          </group>
          <group group_id="O2">
            <title>Standard Care</title>
            <description>Subjects on either study arm with limited disease will receive SBRT to all evident sites of active disease.Subjects on Arm 2 with extensive disease are expected to receive some form of standard systemic therapy (e.g., docetaxel). Subjects on Arm 2 with limited disease may also receive standard systemic therapy following completion of SBRT to all sites of evident disease, at the discretion of the treating physicians.&#xD;
SBRT: For subjects on Arm 1, SBRT will be delivered concurrently with FLT3 ligand during Week 1 of study therapy. If only one lesion is being treated, SBRT should be completed during week 1 (e.g., with daily treatments for a 5-fraction course of treatments every other day for a 3-fraction course). In cases where multiple lesions are being treated with SBRT (Arm 1 or Arm 2) or if treatment is interrupted due to technical issues or intercurrent illness, SBRT may extend beyond Week 1.</description>
          </group>
        </group_list>
        <measure>
          <title>Radiographic Responses Using Descriptive Statistics</title>
          <description>The clinical benefit rate (CBR) will be defined as the percentage of subjects who achieve best response of confirmed CR or PR, or stable disease (SD) for at least four months.</description>
          <population>Data was not collected/aggregated. No analyses conducted.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Quality of Life Using EORTC QLQ-LC13 (Quality of Life Questionnaire, Lung Cancer)</title>
        <description>Summary statistics (mean, standard deviation, median, 25th and 75th percentiles, and range) and the mean change from baseline of linear-transformed scores will be reported for all the items and subscales of the EORTC QLQ-C30 questionnaire and the QLQ-LC13, according to the EORTC scoring manual guidelines. higher scores are a better level of functioning</description>
        <time_frame>1 year</time_frame>
        <population>Data was not collected/aggregated. No analyses conducted.</population>
        <group_list>
          <group group_id="O1">
            <title>FLT3 Ligand (CDX-301), Anti-CD40 Antibody (CDX-1140), and SBRT</title>
            <description>Subjects on either study arm with limited disease will receive SBRT to all evident sites of active disease. Subjects on Arm 1 with extensive disease will initially receive SBRT to a single site of disease but may receive additional &quot;cycles&quot; of FLT3 ligand, anti-CD40 antibody, and SBRT at later time points.&#xD;
FLT3 Ligand (CDX-301): Fms-like tyrosine kinase 3 (FLT3) ligand is a potent hematopoietic growth factor that mobilizes stem cells and greatly increases the number of circulating dendritic cells (DCs) in blood and organs.&#xD;
anti-CD40 antibody (CDX-1140): CD40 is a key molecule in the regulation of immune responses whose activity can be modulated using antibodies. CD40 is a tumor necrosis factor receptor superfamily member expressed on antigen presenting cells, including dendritic cells, as well as a host of other cell types, including a wide range of tumor cells&#xD;
SBRT: For subjects on Arm 1, SBRT will be delivered concurrently with FLT3 ligand during Week 1 of study therapy. If only one lesion is being treated, SBRT should be completed during week 1 (e.g., with daily treatments for a 5-fraction course of treatments every other day for a 3-fraction course). In cases where multiple lesions are being treated with SBRT (Arm 1 or Arm 2) or if treatment is interrupted due to technical issues or intercurrent illness, SBRT may extend beyond Week 1.</description>
          </group>
          <group group_id="O2">
            <title>Standard Care</title>
            <description>Subjects on either study arm with limited disease will receive SBRT to all evident sites of active disease.Subjects on Arm 2 with extensive disease are expected to receive some form of standard systemic therapy (e.g., docetaxel). Subjects on Arm 2 with limited disease may also receive standard systemic therapy following completion of SBRT to all sites of evident disease, at the discretion of the treating physicians.&#xD;
SBRT: For subjects on Arm 1, SBRT will be delivered concurrently with FLT3 ligand during Week 1 of study therapy. If only one lesion is being treated, SBRT should be completed during week 1 (e.g., with daily treatments for a 5-fraction course of treatments every other day for a 3-fraction course). In cases where multiple lesions are being treated with SBRT (Arm 1 or Arm 2) or if treatment is interrupted due to technical issues or intercurrent illness, SBRT may extend beyond Week 1.</description>
          </group>
        </group_list>
        <measure>
          <title>Quality of Life Using EORTC QLQ-LC13 (Quality of Life Questionnaire, Lung Cancer)</title>
          <description>Summary statistics (mean, standard deviation, median, 25th and 75th percentiles, and range) and the mean change from baseline of linear-transformed scores will be reported for all the items and subscales of the EORTC QLQ-C30 questionnaire and the QLQ-LC13, according to the EORTC scoring manual guidelines. higher scores are a better level of functioning</description>
          <population>Data was not collected/aggregated. No analyses conducted.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Quality of Life Using QLQ-C30 (Quality of Life Questionnaire)</title>
        <description>Summary statistics (mean, standard deviation, median, 25th and 75th percentiles, and range) and the mean change from baseline of linear-transformed scores will be reported for all the items and subscales of the EORTC QLQ-C30 questionnaire and the QLQ-LC13, according to the EORTC scoring manual guidelines. Most items are scored 1 to 4, higher scores are a better level of functioning.</description>
        <time_frame>1 year</time_frame>
        <population>Data was not collected/aggregated. No analyses conducted.</population>
        <group_list>
          <group group_id="O1">
            <title>FLT3 Ligand (CDX-301), Anti-CD40 Antibody (CDX-1140), and SBRT</title>
            <description>Subjects on either study arm with limited disease will receive SBRT to all evident sites of active disease. Subjects on Arm 1 with extensive disease will initially receive SBRT to a single site of disease but may receive additional &quot;cycles&quot; of FLT3 ligand, anti-CD40 antibody, and SBRT at later time points.&#xD;
FLT3 Ligand (CDX-301): Fms-like tyrosine kinase 3 (FLT3) ligand is a potent hematopoietic growth factor that mobilizes stem cells and greatly increases the number of circulating dendritic cells (DCs) in blood and organs.&#xD;
anti-CD40 antibody (CDX-1140): CD40 is a key molecule in the regulation of immune responses whose activity can be modulated using antibodies. CD40 is a tumor necrosis factor receptor superfamily member expressed on antigen presenting cells, including dendritic cells, as well as a host of other cell types, including a wide range of tumor cells&#xD;
SBRT: For subjects on Arm 1, SBRT will be delivered concurrently with FLT3 ligand during Week 1 of study therapy. If only one lesion is being treated, SBRT should be completed during week 1 (e.g., with daily treatments for a 5-fraction course of treatments every other day for a 3-fraction course). In cases where multiple lesions are being treated with SBRT (Arm 1 or Arm 2) or if treatment is interrupted due to technical issues or intercurrent illness, SBRT may extend beyond Week 1.</description>
          </group>
          <group group_id="O2">
            <title>Standard Care</title>
            <description>Subjects on either study arm with limited disease will receive SBRT to all evident sites of active disease.Subjects on Arm 2 with extensive disease are expected to receive some form of standard systemic therapy (e.g., docetaxel). Subjects on Arm 2 with limited disease may also receive standard systemic therapy following completion of SBRT to all sites of evident disease, at the discretion of the treating physicians.&#xD;
SBRT: For subjects on Arm 1, SBRT will be delivered concurrently with FLT3 ligand during Week 1 of study therapy. If only one lesion is being treated, SBRT should be completed during week 1 (e.g., with daily treatments for a 5-fraction course of treatments every other day for a 3-fraction course). In cases where multiple lesions are being treated with SBRT (Arm 1 or Arm 2) or if treatment is interrupted due to technical issues or intercurrent illness, SBRT may extend beyond Week 1.</description>
          </group>
        </group_list>
        <measure>
          <title>Quality of Life Using QLQ-C30 (Quality of Life Questionnaire)</title>
          <description>Summary statistics (mean, standard deviation, median, 25th and 75th percentiles, and range) and the mean change from baseline of linear-transformed scores will be reported for all the items and subscales of the EORTC QLQ-C30 questionnaire and the QLQ-LC13, according to the EORTC scoring manual guidelines. Most items are scored 1 to 4, higher scores are a better level of functioning.</description>
          <population>Data was not collected/aggregated. No analyses conducted.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Daily Step Count Using Descriptive Statistics</title>
        <description>Average daily step counts</description>
        <time_frame>1 year</time_frame>
        <population>Data was not collected/aggregated. No analyses conducted.</population>
        <group_list>
          <group group_id="O1">
            <title>FLT3 Ligand (CDX-301), Anti-CD40 Antibody (CDX-1140), and SBRT</title>
            <description>Subjects on either study arm with limited disease will receive SBRT to all evident sites of active disease. Subjects on Arm 1 with extensive disease will initially receive SBRT to a single site of disease but may receive additional &quot;cycles&quot; of FLT3 ligand, anti-CD40 antibody, and SBRT at later time points.&#xD;
FLT3 Ligand (CDX-301): Fms-like tyrosine kinase 3 (FLT3) ligand is a potent hematopoietic growth factor that mobilizes stem cells and greatly increases the number of circulating dendritic cells (DCs) in blood and organs.&#xD;
anti-CD40 antibody (CDX-1140): CD40 is a key molecule in the regulation of immune responses whose activity can be modulated using antibodies. CD40 is a tumor necrosis factor receptor superfamily member expressed on antigen presenting cells, including dendritic cells, as well as a host of other cell types, including a wide range of tumor cells&#xD;
SBRT: For subjects on Arm 1, SBRT will be delivered concurrently with FLT3 ligand during Week 1 of study therapy. If only one lesion is being treated, SBRT should be completed during week 1 (e.g., with daily treatments for a 5-fraction course of treatments every other day for a 3-fraction course). In cases where multiple lesions are being treated with SBRT (Arm 1 or Arm 2) or if treatment is interrupted due to technical issues or intercurrent illness, SBRT may extend beyond Week 1.</description>
          </group>
          <group group_id="O2">
            <title>Standard Care</title>
            <description>Subjects on either study arm with limited disease will receive SBRT to all evident sites of active disease.Subjects on Arm 2 with extensive disease are expected to receive some form of standard systemic therapy (e.g., docetaxel). Subjects on Arm 2 with limited disease may also receive standard systemic therapy following completion of SBRT to all sites of evident disease, at the discretion of the treating physicians.&#xD;
SBRT: For subjects on Arm 1, SBRT will be delivered concurrently with FLT3 ligand during Week 1 of study therapy. If only one lesion is being treated, SBRT should be completed during week 1 (e.g., with daily treatments for a 5-fraction course of treatments every other day for a 3-fraction course). In cases where multiple lesions are being treated with SBRT (Arm 1 or Arm 2) or if treatment is interrupted due to technical issues or intercurrent illness, SBRT may extend beyond Week 1.</description>
          </group>
        </group_list>
        <measure>
          <title>Daily Step Count Using Descriptive Statistics</title>
          <description>Average daily step counts</description>
          <population>Data was not collected/aggregated. No analyses conducted.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>AE data was scheduled to be collected during each clinical visit from the time of participants first treatment on Day 0 through week 49.</time_frame>
      <group_list>
        <group group_id="E1">
          <title>FLT3 Ligand (CDX-301), Anti-CD40 Antibody (CDX-1140), and SBRT</title>
          <description>Subjects on either study arm with limited disease will receive SBRT to all evident sites of active disease. Subjects on Arm 1 with extensive disease will initially receive SBRT to a single site of disease but may receive additional &quot;cycles&quot; of FLT3 ligand, anti-CD40 antibody, and SBRT at later time points.&#xD;
FLT3 Ligand (CDX-301): Fms-like tyrosine kinase 3 (FLT3) ligand is a potent hematopoietic growth factor that mobilizes stem cells and greatly increases the number of circulating dendritic cells (DCs) in blood and organs.&#xD;
anti-CD40 antibody (CDX-1140): CD40 is a key molecule in the regulation of immune responses whose activity can be modulated using antibodies. CD40 is a tumor necrosis factor receptor superfamily member expressed on antigen presenting cells, including dendritic cells, as well as a host of other cell types, including a wide range of tumor cells&#xD;
SBRT: For subjects on Arm 1, SBRT will be delivered concurrently with FLT3 ligand during Week 1 of study therapy. If only one lesion is being treated, SBRT should be completed during week 1 (e.g., with daily treatments for a 5-fraction course of treatments every other day for a 3-fraction course). In cases where multiple lesions are being treated with SBRT (Arm 1 or Arm 2) or if treatment is interrupted due to technical issues or intercurrent illness, SBRT may extend beyond Week 1.</description>
        </group>
        <group group_id="E2">
          <title>Standard Care</title>
          <description>Subjects on either study arm with limited disease will receive SBRT to all evident sites of active disease.Subjects on Arm 2 with extensive disease are expected to receive some form of standard systemic therapy (e.g., docetaxel). Subjects on Arm 2 with limited disease may also receive standard systemic therapy following completion of SBRT to all sites of evident disease, at the discretion of the treating physicians.&#xD;
SBRT: For subjects on Arm 1, SBRT will be delivered concurrently with FLT3 ligand during Week 1 of study therapy. If only one lesion is being treated, SBRT should be completed during week 1 (e.g., with daily treatments for a 5-fraction course of treatments every other day for a 3-fraction course). In cases where multiple lesions are being treated with SBRT (Arm 1 or Arm 2) or if treatment is interrupted due to technical issues or intercurrent illness, SBRT may extend beyond Week 1.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>CTCAE (5.0)</default_vocab>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Sepsis</sub_title>
                <description>Septic Shock</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Lung Infection</sub_title>
                <description>Pneumonia</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Fall</sub_title>
                <description>Fall</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Seizure</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Muscle weakness left-sided</sub_title>
                <description>Muscle weakness left-sided</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Dysarthria</sub_title>
                <description>Dysarthria</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>Pelvic Pain</sub_title>
                <description>Recurrent hip pain leading to hospitalization</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Respiratory Failure</sub_title>
                <description>Hypoxic Respiratory Failure</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>CTCAE (5.0)</default_vocab>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="2"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anemia</sub_title>
                <counts group_id="E1" events="8" subjects_affected="2" subjects_at_risk="2"/>
                <counts group_id="E2" events="13" subjects_affected="2" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Thrombocytopenia</sub_title>
                <counts group_id="E1" events="3" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fatigue/Weakness</sub_title>
                <counts group_id="E1" events="8" subjects_affected="2" subjects_at_risk="2"/>
                <counts group_id="E2" events="4" subjects_affected="3" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Phlebitis</sub_title>
                <description>Related to gemcitabine</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Dermatitis Radiation</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Alkaline Phosphatase Increased</sub_title>
                <counts group_id="E1" events="5" subjects_affected="2" subjects_at_risk="2"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Aspartate Aminotransferase Increased</sub_title>
                <counts group_id="E1" events="5" subjects_affected="2" subjects_at_risk="2"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Alanine Aminotransferase Increased</sub_title>
                <counts group_id="E1" events="7" subjects_affected="2" subjects_at_risk="2"/>
                <counts group_id="E2" events="5" subjects_affected="2" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Alkaline Phosphatase Increased</sub_title>
                <description>Alkaline Phosphatase Increased</description>
                <counts group_id="E1" events="5" subjects_affected="2" subjects_at_risk="2"/>
                <counts group_id="E2" events="4" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Creatinine Increased</sub_title>
                <counts group_id="E1" events="3" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Lymphocyte Count Decreased</sub_title>
                <counts group_id="E1" events="4" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E2" events="5" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Blood Bilirubin Increased</sub_title>
                <counts group_id="E1" events="7" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>GGT Increased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Platelet count decreased</sub_title>
                <counts group_id="E1" events="4" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Hyponatremia</sub_title>
                <counts group_id="E1" events="7" subjects_affected="2" subjects_at_risk="2"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Hypocalcemia</sub_title>
                <counts group_id="E1" events="4" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E2" events="6" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Hypoalbuminemia</sub_title>
                <counts group_id="E1" events="5" subjects_affected="2" subjects_at_risk="2"/>
                <counts group_id="E2" events="4" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Hypercalcemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Hypokalemia</sub_title>
                <counts group_id="E1" events="4" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Hypoglycemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="3" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Hypomagnesemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Glucose intolerance</sub_title>
                <counts group_id="E1" events="4" subjects_affected="2" subjects_at_risk="2"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Hyperphosphatemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Hypertriglyceridemia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Hyperglycemia</sub_title>
                <counts group_id="E1" events="3" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Hyperkalemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Anorexia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Back Pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Myalgia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Left arm weakness</sub_title>
                <description>Upper limb weakness</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Brain metastases</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Slurred speech</sub_title>
                <description>Dysarthria</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" events="3" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Anxiety</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Acute kidney injury</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Dyspnea/Shortness of Breath</sub_title>
                <counts group_id="E1" events="5" subjects_affected="2" subjects_at_risk="2"/>
                <counts group_id="E2" events="3" subjects_affected="2" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Asthma</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" events="5" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Dr. Nitin Ohri</name_or_title>
      <organization>Albert Einstein College of Medicine</organization>
      <phone>718-405-8550</phone>
      <email>nitin.ohri@einsteinmed.edu</email>
    </point_of_contact>
  </clinical_results>
</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/NCT04491084
org study id: 2020-11868
nct id: NCT04491084
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
The purpose of this study is to test a new way of treating the most common form of lung
      cancer. The investigators are testing a combination of radiotherapy with two new forms of
      immunotherapy. This study is testing the safety and effectiveness of this treatment approach
      as compared to standard treatment options.
This is a randomized, open-label phase I/II study. Subjects will be randomized in a 1:1 ratio
      to receive FLT3 ligand (CDX-301), anti-CD40 antibody (CDX-1140) and SBRT (Arm 1) versus
      standard care (Arm 2). Subjects on either study arm with limited disease will receive SBRT to
      all evident sites of active disease. Subjects on Arm 1 with extensive disease will initially
      receive SBRT to a single site of disease but may receive additional "cycles" of FLT3 ligand
      (CDX-301) anti-CD40 antibody (CDX-1140), and SBRT at later time points. Subjects on Arm 2
      with extensive disease are expected to receive some form of standard systemic therapy (e.g.,
      docetaxel). Subjects on Arm 2 with limited disease may also receive standard systemic therapy
      following completion of SBRT to all sites of evident disease, at the discretion of the
      treating physicians. All subjects will be followed closely for treatment-related toxicities.
      Whole-body PET/CT and CT imaging will be performed prior to study entry, and restaging CT
      will be performed every 8 weeks thereafter.

      In the phase I component of this study, subjects will be randomized between study arms until
      6 subjects have been randomized to Arm 1. Study accrual will then be halted until 8 weeks
      after the last study subject begins treatment.

      If the pre-specified safety criteria are achieved in the Phase I portion of this study, the
      study will proceed to phase II. The total sample size (Phase I and Phase II) will be 46
      subjects. All 46 subjects will be included in efficacy analyses.

      If the pre-specified safety criteria are not achieved in the Phase I portion of this study,
      the investigators and Celldex will review safety data from this trial as well as other trials
      using CDX-301 and CDX-1140 and determine if the experimental treatment regimen should be
      altered (e.g., by reducing the CDX-1140 dose). The study protocol would be amended
      accordingly, and Phase I component with the new treatment regimen would be added.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: This is a randomized, open-label phase I/II study. Subjects will be randomized in a 1:1 ratio to receive FLT3 ligand (CDX-301), anti-CD40 antibody (CDX-1140) and SBRT (Arm 1) versus standard care (Arm 2).
primary purpose: Treatment
masking: None (Open Label)
measure: Phase I: Dose-limiting Toxicity (DLT), Defined as Follows:
time frame: up to 8 weeks after initiation of study therapy
description: Death
Any ≥ Grade 3 non-hematological toxicity, with the following exceptions:
Grade 3 alopecia, vitiligo, or endocrinopathies controlled by hormone replacement therapy Grade 3 nausea that resolves to ≤ grade 2 with or without treatment within 72 hours Grade 3 vomiting and diarrhea that resolves to ≤ grade 2 with or without treatment within 72 hours Grade 3 fatigue that resolves to ≤ grade 2 within 5 days Grade 3 hypertension in the absence of maximal medical therapy Grade 3 adverse event of tumor flare (defined as local pain, irritation, or rash localized at sites of known or suspected tumor) of ≤ 7 days in duration Grade 3 amylase or lipase abnormalities that are not associated with symptoms or clinical manifestations of pancreatitis. It is recommended to consult with the Principal Investigator for grade 4 amylase or lipase abnormalities
Grade 3 clinically significant laboratory abnormalities that are asymptomatic and can be reversed within 72 hours, however:
Any Grade 4
measure: Phase II: Progression-free Survival (PFS) Duration
time frame: defined as time from study registration until disease progression (scored using iRECIST) or death, whichever comes first up to 51 weeks.
measure: Overall Survival (OS) Duration
time frame: From date of registration until the date of death from any cause, assessed up to 2 years
description: Length of time that patient survives from time of study registration
measure: Radiographic Responses Using Descriptive Statistics
time frame: From date of registration, assessed up to 4 months
description: The clinical benefit rate (CBR) will be defined as the percentage of subjects who achieve best response of confirmed CR or PR, or stable disease (SD) for at least four months.
measure: Quality of Life Using EORTC QLQ-LC13 (Quality of Life Questionnaire, Lung Cancer)
time frame: 1 year
description: Summary statistics (mean, standard deviation, median, 25th and 75th percentiles, and range) and the mean change from baseline of linear-transformed scores will be reported for all the items and subscales of the EORTC QLQ-C30 questionnaire and the QLQ-LC13, according to the EORTC scoring manual guidelines. higher scores are a better level of functioning
measure: Quality of Life Using QLQ-C30 (Quality of Life Questionnaire)
time frame: 1 year
description: Summary statistics (mean, standard deviation, median, 25th and 75th percentiles, and range) and the mean change from baseline of linear-transformed scores will be reported for all the items and subscales of the EORTC QLQ-C30 questionnaire and the QLQ-LC13, according to the EORTC scoring manual guidelines. Most items are scored 1 to 4, higher scores are a better level of functioning.
measure: Daily Step Count Using Descriptive Statistics
time frame: 1 year
description: Average daily step counts
arm group label: FLT3 ligand (CDX-301), anti-CD40 antibody (CDX-1140), and SBRT
arm group type: Experimental
description: Subjects on either study arm with limited disease will receive SBRT to all evident sites of active disease. Subjects on Arm 1 with extensive disease will initially receive SBRT to a single site of disease but may receive additional "cycles" of FLT3 ligand, anti-CD40 antibody, and SBRT at later time points.
arm group label: Standard care
arm group type: Active Comparator
description: Subjects on either study arm with limited disease will receive SBRT to all evident sites of active disease.Subjects on Arm 2 with extensive disease are expected to receive some form of standard systemic therapy (e.g., docetaxel). Subjects on Arm 2 with limited disease may also receive standard systemic therapy following completion of SBRT to all sites of evident disease, at the discretion of the treating physicians.
intervention type: Drug
intervention name: FLT3 Ligand (CDX-301)
description: Fms-like tyrosine kinase 3 (FLT3) ligand is a potent hematopoietic growth factor that mobilizes stem cells and greatly increases the number of circulating dendritic cells (DCs) in blood and organs.
arm group label: FLT3 ligand (CDX-301), anti-CD40 antibody (CDX-1140), and SBRT
intervention type: Biological
intervention name: anti-CD40 antibody (CDX-1140)
description: CD40 is a key molecule in the regulation of immune responses whose activity can be modulated using antibodies. CD40 is a tumor necrosis factor receptor superfamily member expressed on antigen presenting cells, including dendritic cells, as well as a host of other cell types, including a wide range of tumor cells
arm group label: FLT3 ligand (CDX-301), anti-CD40 antibody (CDX-1140), and SBRT
intervention type: Radiation
intervention name: SBRT
description: For subjects on Arm 1, SBRT will be delivered concurrently with FLT3 ligand during Week 1 of study therapy. If only one lesion is being treated, SBRT should be completed during week 1 (e.g., with daily treatments for a 5-fraction course of treatments every other day for a 3-fraction course). In cases where multiple lesions are being treated with SBRT (Arm 1 or Arm 2) or if treatment is interrupted due to technical issues or intercurrent illness, SBRT may extend beyond Week 1.
arm group label: FLT3 ligand (CDX-301), anti-CD40 antibody (CDX-1140), and SBRT
arm group label: Standard care
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Albert Einstein College of Medicine
investigator full name: Nitin Ohri
investigator title: Associate Professor
mesh term: Lung Neoplasms
mesh term: Carcinoma, Non-Small-Cell Lung
mesh term: Antibodies
mesh term: Flt3 ligand protein
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