<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/NCT04499053</url>
  </required_header>
  <id_info>
    <org_study_id>STUDY00002036</org_study_id>
    <nct_id>NCT04499053</nct_id>
  </id_info>
  <brief_title>Durvalumab and Tremelimumab in Combination With Chemotherapy in Virus-infected Patients With Non-small Cell Lung Cancer</brief_title>
  <official_title>A Phase II Trial of Durvalumab (MEDI4736) and Tremelimumab in Combination With Chemotherapy in Virus-infected Patients With Non-small Cell Lung Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Georgetown University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>AstraZeneca</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Georgetown University</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>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a phase II trial of durvalumab and tremelimumab in combination of platinum-based&#xD;
      chemotherapy. Patients with stage IV Non-Small-Cell-Lung Cancer (NSCLC) with human&#xD;
      immunodeficiency virus (HIV) infection (cohort 1) or hepatitis B virus (HBV), or hepatitis C&#xD;
      virus (HCV) infection (cohort 2) will be eligible. Patients will receive standard&#xD;
      platinum-based chemotherapy plus durvalumab for 4 cycles (every 3 weeks), followed by&#xD;
      durvalumab (with or without pemetrexed for non-squamous NSCLC) maintenance therapy. It is&#xD;
      hypothesized that Durvalumab and tremelimumab in combination with standard chemotherapy is&#xD;
      safe and effective for the treatment of stage IV NSCLC in patients with HIV, HBV, or HCV&#xD;
      infection.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is an open-label, non-randomized phase II trial of durvalumab and tremelimumab in&#xD;
      combination with platinum-based doublet chemotherapy. Patients with stage IV NSCLC with HIV&#xD;
      (cohort 1) or HBV/HCV (cohort 2) infection will be eligible. Patients will receive standard&#xD;
      chemotherapy plus durvalumab (1500 mg) and tremelimumab (75 mg) every three weeks for 4&#xD;
      cycles, followed by maintenance treatment with durvalumab (1500 mg Q4W; with or without&#xD;
      pemetrexed for non-squamous NSCLC per the discretion of the investigator). A dose of&#xD;
      tremelimumab 75 mg will be given at week 16.&#xD;
&#xD;
      Patient will be enrolled into the trial using an optimal two-stage phase II trial design. If&#xD;
      0 of the 7 achieved a response, no further patients will be enrolled in that cohort. If 1 or&#xD;
      more of the first 7 patients has a response, accrual would continue until a total of 18&#xD;
      patients have been enrolled in that cohort. Objective response will be evaluated using the&#xD;
      Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Safety and tolerability will be&#xD;
      evaluated by assessing the incidence of treatment-related grade 3 or higher AEs.&#xD;
      Treatment-related grade 3 or higher AEs will be defined as any grade 3 or higher AEs that&#xD;
      occur during the first 42 days of treatment and are related to the study treatment. AEs will&#xD;
      be evaluated using the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.&#xD;
&#xD;
      Subjects will receive 4 cycles of combination treatment: durvalumab (1500 mg every 3 weeks)&#xD;
      and tremelimumab (75 mg every 3 weeks) in combination with platinum-based doublet&#xD;
      chemotherapy. The platinum-based doublet chemotherapies (carboplatin plus&#xD;
      paclitaxel/nab-paclitaxel vs. pemetrexed plus carboplatin/cisplatin) are dependent on the&#xD;
      tumor histology of the subject (squamous vs. non-squamous). Only subjects who achieve stable&#xD;
      disease or better radiological response after 4 cycles of induction treatment will be&#xD;
      eligible to continue study treatment in maintenance. The choice to treat non-squamous&#xD;
      subjects with pemetrexed maintenance after the 4 induction cycles will be determined by the&#xD;
      investigator.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">December 9, 2020</start_date>
  <completion_date type="Anticipated">September 2023</completion_date>
  <primary_completion_date type="Anticipated">September 2023</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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Adverse Events</measure>
    <time_frame>At the end of Cycle 4 (each cycle is 3 weeks)</time_frame>
    <description>Incidence of treatment-emergent Adverse Events according to NCI CTCAE v5.0.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Radiological Response</measure>
    <time_frame>At the end of Cycle 4 (each cycle is 3 weeks)</time_frame>
    <description>Radiological response will be evaluated using Recist Version 1.1 Criteria</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Changes in Viral Load</measure>
    <time_frame>At the end of Cycle 4 (each cycle is 3 weeks)</time_frame>
    <description>Evaluate changes in viral load with study treatment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Cytokine Secretion Assays</measure>
    <time_frame>36 months</time_frame>
    <description>Cytokine secretion assays will be performed on blood samples before, during, and after treatment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Correlation of Multiplex IHC to response</measure>
    <time_frame>36 months</time_frame>
    <description>Baseline immune biomarkers (e.g. PD-L1 expression, composition of T cells in tumor microenvironment) using multiplex IHC will be compared between responders and non-responders to find predictive biomarkers associated with response to treatment.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">18</enrollment>
  <condition>Carcinoma, Non-Small Cell Lung</condition>
  <arm_group>
    <arm_group_label>durvalumab (MEDI4736) and tremelimumab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Durvalumab in combination with tremelimumab and platinum-based doublet chemotherapy. Only subjects who achieve stable disease or better radiological response after 4 cycles of induction treatment will be eligible to continue study treatment with durvalumab in maintenance.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Durvalumab</intervention_name>
    <description>durvalumab 1500 mg, intravenous, every 3 weeks for 4 cycles, followed by 1500 mg, intravenous, every 4 weeks (maintenance treatment)</description>
    <arm_group_label>durvalumab (MEDI4736) and tremelimumab</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tremelimumab</intervention_name>
    <description>tremelimumab 75 mg, intravenous, every 3 weeks for 4 cycles. A dose of tremelimumab 75 mg will be given at week 16.</description>
    <arm_group_label>durvalumab (MEDI4736) and tremelimumab</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Patients with stage IV NSCLC who had undergone no previous systemic therapy for stage&#xD;
             IV disease.&#xD;
&#xD;
          2. Cohort 1: Patients with HIV must be on an effective combination anti-retroviral&#xD;
             therapy (cART) regimen for ≥ 4 weeks. Also, patients need to meet the following&#xD;
             criteria.&#xD;
&#xD;
               -  Documented HIV viral load &lt; 400 copies/mL&#xD;
&#xD;
               -  No AIDS-defining opportunistic infections within the last 12 months&#xD;
&#xD;
               -  No concurrent incurable AIDS-defining malignancy&#xD;
&#xD;
             Cohort 2:&#xD;
&#xD;
             HBV: Patients with chronic HBV infection (defined by persistence of HBsAg for more&#xD;
             than six months) will be eligible. Patients with positive hepatitis B core antibody&#xD;
             (anti-HBc) but negative surface antigen (HBsAg) will also be eligible. Those with&#xD;
             detectable HBV DNA who are negative for HBsAg will also be eligible.&#xD;
&#xD;
             o HBV-positive patients who are HBsAg positive with evidence of active disease should&#xD;
             be on anti-HBV therapy prior to starting study therapy.&#xD;
&#xD;
             HCV: Patients with detectable HCV RNA will be eligible if they are on appropriate&#xD;
             anti-HCV therapy. Those who have completed antiviral therapy for HCV and undetectable&#xD;
             HCV RNA will also be eligible.&#xD;
&#xD;
          3. Age &gt; 18 years at time of study entry.&#xD;
&#xD;
          4. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2&#xD;
&#xD;
          5. Body weight &gt;30kg&#xD;
&#xD;
          6. Adequate normal organ and marrow function as defined below:&#xD;
&#xD;
               -  Hemoglobin ≥ 9.0 g/dL&#xD;
&#xD;
               -  Absolute neutrophil count (ANC) ≥ 1,000 per mm3&#xD;
&#xD;
               -  Platelet count ≥ 100,000 per mm3&#xD;
&#xD;
               -  CD4 T-cell count ≥ 100 per mm3 for HIV-infected patients&#xD;
&#xD;
               -  Serum bilirubin ≤1.5 x institutional upper limit of normal (ULN). This will not&#xD;
                  apply to patients with confirmed Gilbert's syndrome (persistent or recurrent&#xD;
                  hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis&#xD;
                  or hepatic pathology), who will be allowed only in consultation with their&#xD;
                  physician.&#xD;
&#xD;
               -  AST (SGOT)/ALT (SGPT) ≤2.5 x institutional upper limit of normal unless liver&#xD;
                  metastases are present, in which case it must be ≤5x ULN&#xD;
&#xD;
               -  Measured creatinine clearance (CL) &gt;40 mL/min or Calculated creatinine CL&gt;40&#xD;
                  mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour&#xD;
                  urine collection for determination of creatinine clearance:&#xD;
&#xD;
             Males: Creatinine CL (mL/min) = [Weight (kg) x (140 - Age)] / [72 x serum creatinine&#xD;
             (mg/dL)] Females: Creatinine CL (mL/min) = [Weight (kg) x (140 - Age) x 0.85] / [72 x&#xD;
             serum creatinine (mg/dL)]&#xD;
&#xD;
          7. Evidence of post-menopausal status or negative urinary or serum pregnancy test for&#xD;
             female pre-menopausal patients. Women will be considered post-menopausal if they have&#xD;
             been amenorrheic for 12 months without an alternative medical cause. The following&#xD;
             age-specific requirements apply:&#xD;
&#xD;
               -  Women &lt;50 years of age would be considered post-menopausal if they have been&#xD;
                  amenorrheic for 12 months or more following cessation of exogenous hormonal&#xD;
                  treatments and if they have luteinizing hormone and follicle-stimulating hormone&#xD;
                  levels in the post-menopausal range for the institution or underwent surgical&#xD;
                  sterilization (bilateral oophorectomy or hysterectomy).&#xD;
&#xD;
               -  Women ≥50 years of age would be considered post-menopausal if they have been&#xD;
                  amenorrheic for 12 months or more following cessation of all exogenous hormonal&#xD;
                  treatments, had radiation-induced menopause with last menses &gt;1 year ago, had&#xD;
                  chemotherapy-induced menopause with last menses &gt;1 year ago, or underwent&#xD;
                  surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or&#xD;
                  hysterectomy).&#xD;
&#xD;
          8. Patient is willing and able to comply with the protocol for the duration of the study&#xD;
             including undergoing treatment and scheduled visits and examinations including follow&#xD;
             up.&#xD;
&#xD;
          9. Must have a life expectancy of at least 12 weeks.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Sensitizing EGFR mutations (deletion in exon 19, L858R in exon 21, G719X, and L861Q)&#xD;
             and/or ALK translocations by locally approved laboratory testing including blood-based&#xD;
             liquid biopsy.&#xD;
&#xD;
          2. 2. Coinfection of HIV + HBV (coinfection of HIV and HBV allowed if the patient is on&#xD;
             appropriate anti-viral therapy for HBV) or HIV + HCV (coinfection of HIV and HCV&#xD;
             allowed if HCV is cured or patient is on appropriate anti-viral therapy for hepatitis&#xD;
             C). Coinfection of HBV and HCV is allowed if otherwise eligible.&#xD;
&#xD;
          3. No measurable disease.&#xD;
&#xD;
          4. Receipt of the last dose of anticancer therapy (chemotherapy, targeted therapy) ≤ 21&#xD;
             days prior to the first dose of study treatment.&#xD;
&#xD;
          5. Any unresolved toxicity NCI CTCAE Grade ≥ 2 from previous anticancer therapy&#xD;
             (chemotherapy, targeted therapy, radiation therapy) with the exception of alopecia,&#xD;
             vitiligo, and the laboratory values defined in the inclusion criteria.&#xD;
&#xD;
          6. Patients who have had whole brain radiation therapy (WBRT) during the previous 2 weeks&#xD;
             before treatment (no washout period is required for patients who have received&#xD;
             stereotactic body radiation therapy).&#xD;
&#xD;
          7. Subject has had major surgery (e.g., intra-thoracic, intra-abdominal or intra-pelvic)&#xD;
             within 4 weeks prior to starting study drug or has not recovered from side effects of&#xD;
             such procedure (≥ grade 2 AE related to such procedure). Video-assisted thoracic&#xD;
             surgery (VATS) and mediastinoscopy will not be counted as major surgery and subject&#xD;
             can be enrolled in the study ≥ 1 week after the procedure.&#xD;
&#xD;
          8. History of allogenic organ transplantation.&#xD;
&#xD;
          9. Active or prior documented autoimmune or inflammatory disorders (including&#xD;
             inflammatory bowel disease [e.g., colitis or Crohn's disease], systemic lupus&#xD;
             erythematosus, Sarcoidosis syndrome, or Wegener syndrome [granulomatosis with&#xD;
             polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc]). The&#xD;
             following are exceptions to this criterion:&#xD;
&#xD;
             i. Patients with vitiligo or alopecia ii. Patients with hypothyroidism (e.g.,&#xD;
             following Hashimoto syndrome) stable on hormone replacement iii. Any chronic skin&#xD;
             condition that does not require systemic therapy iv. Patients without active disease&#xD;
             in the last 5 years may be included&#xD;
&#xD;
         10. Uncontrolled intercurrent illness, including but not limited to, ongoing or active&#xD;
             infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable&#xD;
             angina pectoris, cardiac arrhythmia, interstitial lung disease, or psychiatric&#xD;
             illness/social situations that would limit compliance with study requirement,&#xD;
             substantially increase risk of incurring AEs or compromise the ability of the patient&#xD;
             to give written informed consent.&#xD;
&#xD;
         11. Patients with prior or concurrent malignancy whose natural history or treatment does&#xD;
             not have the potential to interfere with the safety or efficacy assessment of the&#xD;
             investigational regimen are eligible for this trial.&#xD;
&#xD;
         12. Previously untreated central nervous system (CNS) metastases or leptomeningeal&#xD;
             disease. Patients who have had whole brain radiation therapy (WBRT) during the&#xD;
             previous 2 weeks before treatment (no washout period is required for patients who have&#xD;
             received stereotactic body radiation therapy).&#xD;
&#xD;
         13. Active tuberculosis (clinical evaluation that includes clinical history, physical&#xD;
             examination and radiographic findings, and TB testing in line with local practice).&#xD;
&#xD;
         14. Current or prior use of immunosuppressive medication within 7 days before the first&#xD;
             dose of durvalumab. The following are exceptions to this criterion:&#xD;
&#xD;
             i. Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra&#xD;
             articular injection) ii. Systemic corticosteroids at doses not to exceed 20 mg/day of&#xD;
             prednisone or its equivalent iii. Steroids as premedication for hypersensitivity&#xD;
             reactions (e.g., CT scan premedication) iv. Decreasing dose of systemic&#xD;
             corticosteroids after radiation therapy for brain metastasis.&#xD;
&#xD;
         15. Receipt of live attenuated vaccine within 30 days prior to the first dose of&#xD;
             investigational product (IP). Note: Patients, if enrolled, should not receive live&#xD;
             vaccine whilst receiving study treatment and up to 30 days after the last dose of IP.&#xD;
&#xD;
         16. Female patients who are pregnant or breastfeeding or male or female patients of&#xD;
             reproductive potential who are not willing to employ effective birth control.&#xD;
&#xD;
         17. Known allergy or hypersensitivity to any of the study drugs or any of the study drug&#xD;
             excipients.&#xD;
&#xD;
         18. Patients who have received prior anti-PD-1, anti PD-L1 or anti CTLA-4 within 12 months&#xD;
             of the first dose of durvalumab.&#xD;
&#xD;
         19. Judgment by the investigator that the patient is unsuitable to participate in the&#xD;
             study and the patient is unlikely to comply with study procedures, restrictions and&#xD;
             requirements.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Chul Kim, MD</last_name>
    <role>Study Chair</role>
    <affiliation>Georgetown University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Georgetown Lombardi Comprehensive Cancer Center</name>
      <address>
        <city>Washington</city>
        <state>District of Columbia</state>
        <zip>20007</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Ashlyn Wallace</last_name>
      <phone>202-687-4773</phone>
      <email>aew72@georgetown.edu</email>
    </contact>
    <investigator>
      <last_name>Chul Kim, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Medstar Washington Hospital Center</name>
      <address>
        <city>Washington</city>
        <state>District of Columbia</state>
        <zip>20010</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Leila Sounna</last_name>
      <phone>202-877-4775</phone>
      <email>Leila.Sounna@medstar.net</email>
    </contact>
    <investigator>
      <last_name>Irena Veytsman, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Harry and Jeannette Weinberg Cancer Institute at Franklin Square</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21237</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Amy Avergas</last_name>
      <phone>443-777-8876</phone>
      <email>amy.m.avergas@medstar.net</email>
    </contact>
    <investigator>
      <last_name>Kevin Chen, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>March 2023</verification_date>
  <study_first_submitted>July 14, 2020</study_first_submitted>
  <study_first_submitted_qc>July 30, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">August 5, 2020</study_first_posted>
  <last_update_submitted>March 7, 2023</last_update_submitted>
  <last_update_submitted_qc>March 7, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">March 9, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Lung Cancer</keyword>
  <keyword>Non-Small Cell Lung Cancer</keyword>
  <keyword>Durvalumab</keyword>
  <keyword>Tremelimumab</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>Durvalumab</mesh_term>
    <mesh_term>Tremelimumab</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04499053
org study id: STUDY00002036
nct id: NCT04499053
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
This is a phase II trial of durvalumab and tremelimumab in combination of platinum-based
      chemotherapy. Patients with stage IV Non-Small-Cell-Lung Cancer (NSCLC) with human
      immunodeficiency virus (HIV) infection (cohort 1) or hepatitis B virus (HBV), or hepatitis C
      virus (HCV) infection (cohort 2) will be eligible. Patients will receive standard
      platinum-based chemotherapy plus durvalumab for 4 cycles (every 3 weeks), followed by
      durvalumab (with or without pemetrexed for non-squamous NSCLC) maintenance therapy. It is
      hypothesized that Durvalumab and tremelimumab in combination with standard chemotherapy is
      safe and effective for the treatment of stage IV NSCLC in patients with HIV, HBV, or HCV
      infection.
This is an open-label, non-randomized phase II trial of durvalumab and tremelimumab in
      combination with platinum-based doublet chemotherapy. Patients with stage IV NSCLC with HIV
      (cohort 1) or HBV/HCV (cohort 2) infection will be eligible. Patients will receive standard
      chemotherapy plus durvalumab (1500 mg) and tremelimumab (75 mg) every three weeks for 4
      cycles, followed by maintenance treatment with durvalumab (1500 mg Q4W; with or without
      pemetrexed for non-squamous NSCLC per the discretion of the investigator). A dose of
      tremelimumab 75 mg will be given at week 16.

      Patient will be enrolled into the trial using an optimal two-stage phase II trial design. If
      0 of the 7 achieved a response, no further patients will be enrolled in that cohort. If 1 or
      more of the first 7 patients has a response, accrual would continue until a total of 18
      patients have been enrolled in that cohort. Objective response will be evaluated using the
      Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Safety and tolerability will be
      evaluated by assessing the incidence of treatment-related grade 3 or higher AEs.
      Treatment-related grade 3 or higher AEs will be defined as any grade 3 or higher AEs that
      occur during the first 42 days of treatment and are related to the study treatment. AEs will
      be evaluated using the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.

      Subjects will receive 4 cycles of combination treatment: durvalumab (1500 mg every 3 weeks)
      and tremelimumab (75 mg every 3 weeks) in combination with platinum-based doublet
      chemotherapy. The platinum-based doublet chemotherapies (carboplatin plus
      paclitaxel/nab-paclitaxel vs. pemetrexed plus carboplatin/cisplatin) are dependent on the
      tumor histology of the subject (squamous vs. non-squamous). Only subjects who achieve stable
      disease or better radiological response after 4 cycles of induction treatment will be
      eligible to continue study treatment in maintenance. The choice to treat non-squamous
      subjects with pemetrexed maintenance after the 4 induction cycles will be determined by the
      investigator.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Adverse Events
time frame: At the end of Cycle 4 (each cycle is 3 weeks)
description: Incidence of treatment-emergent Adverse Events according to NCI CTCAE v5.0.
measure: Radiological Response
time frame: At the end of Cycle 4 (each cycle is 3 weeks)
description: Radiological response will be evaluated using Recist Version 1.1 Criteria
measure: Changes in Viral Load
time frame: At the end of Cycle 4 (each cycle is 3 weeks)
description: Evaluate changes in viral load with study treatment
measure: Change in Cytokine Secretion Assays
time frame: 36 months
description: Cytokine secretion assays will be performed on blood samples before, during, and after treatment.
measure: Correlation of Multiplex IHC to response
time frame: 36 months
description: Baseline immune biomarkers (e.g. PD-L1 expression, composition of T cells in tumor microenvironment) using multiplex IHC will be compared between responders and non-responders to find predictive biomarkers associated with response to treatment.
arm group label: durvalumab (MEDI4736) and tremelimumab
arm group type: Experimental
description: Durvalumab in combination with tremelimumab and platinum-based doublet chemotherapy. Only subjects who achieve stable disease or better radiological response after 4 cycles of induction treatment will be eligible to continue study treatment with durvalumab in maintenance.
intervention type: Drug
intervention name: Durvalumab
description: durvalumab 1500 mg, intravenous, every 3 weeks for 4 cycles, followed by 1500 mg, intravenous, every 4 weeks (maintenance treatment)
arm group label: durvalumab (MEDI4736) and tremelimumab
intervention type: Drug
intervention name: Tremelimumab
description: tremelimumab 75 mg, intravenous, every 3 weeks for 4 cycles. A dose of tremelimumab 75 mg will be given at week 16.
arm group label: durvalumab (MEDI4736) and tremelimumab
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Chul Kim, MD
role: Study Chair
affiliation: Georgetown University
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
mesh term: Durvalumab
mesh term: Tremelimumab
sharing ipd: No