<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/NCT03819465</url>
  </required_header>
  <id_info>
    <org_study_id>D933IC00001</org_study_id>
    <secondary_id>2018-001748-74</secondary_id>
    <nct_id>NCT03819465</nct_id>
  </id_info>
  <brief_title>A Study of Novel Anti-cancer Agents in Patients With Previously Untreated NSCLC</brief_title>
  <acronym>MAGELLAN</acronym>
  <official_title>A Phase IB, Open-Label, Multi-Center Study to Determine the Efficacy and Safety of Durvalumab and/or Novel Oncology Therapies, With or Without Chemotherapy, for First-Line Stage IV Non-Small Cell Lung Cancer (NSCLC) (MAGELLAN)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>AstraZeneca</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>AstraZeneca</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study is designed to determine the efficacy and safety of durvalumab and/or novel&#xD;
      oncology therapies, with or without chemotherapy, for first-line Stage IV Non-Small Cell Lung&#xD;
      Cancer (NSCLC)&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a Phase IB, Open-Label, Multi-Center Study to Determine the Efficacy and Safety of&#xD;
      Durvalumab and/or Novel Oncology Therapies, With or Without Chemotherapy, for First-Line&#xD;
      Stage IV Non-Small Cell Lung Cancer (NSCLC).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">December 27, 2018</start_date>
  <completion_date type="Anticipated">May 23, 2023</completion_date>
  <primary_completion_date type="Anticipated">May 23, 2023</primary_completion_date>
  <phase>Phase 1</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>Treatment arms for MEDI5752 (Arms A4 and B4) will enroll 42 and 60 patients, respectively. Arm B5 (AZD2936+chemotherapy) will enroll 60 patients.&#xD;
For all other treatment arms, 30 patients will be enrolled into each arm; additional patients may be enrolled in order to have 30 evaluable patients per arm (ie, dosed).</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Assessment of AEs by CTCAE v5.0</measure>
    <time_frame>From informed consent until the safety follow-up visit 3 months after the last dose of study drug, or until the final data cut-off (DCO) date, whichever is earlier.</time_frame>
    <description>Assessment of safety and tolerability of each treatment arm</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Objective Response Rate (ORR)</measure>
    <time_frame>Tumor assessments every 6-9 weeks until week 48-54, then every 12 or 18 weeks, depending on treatment arm until the earliest of radiological progression, death, withdrawal of consent, or final DCO (approximately 4 months after last patient randomized).</time_frame>
    <description>Assessment of the efficacy of each treatment arm according to RECIST 1.1. ORR: The percentage of evaluable patients with a confirmed Investigator-assessed visit response of CR or PR</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of Response (DoR)</measure>
    <time_frame>Tumor assessments every 6-9 weeks until week 48-54, then every 12 or 18 weeks, depending on treatment arm until the earliest of radiological progression, death, withdrawal of consent, or final DCO (approximately 4 months after last patient randomized).</time_frame>
    <description>Assessment of the efficacy of each treatment arm according to RECIST 1.1. DoR: Time from date of first detection of objective response until the date of objective radiological disease progression</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression Free Survival (PFS)</measure>
    <time_frame>Tumor assessments every 6-9 weeks until week 48-54, then every 12/18 weeks based on arm until progression, death, withdrawal or final DCO. Further PFS data will be collected until 6 months after last patient dosed or final DCO</time_frame>
    <description>Assessment of the efficacy of each treatment arm according to RECIST 1.1. PFS: Time from date of treatment assignment until the date of objective radiological disease progression using RECIST 1.1 or death (by any cause in the absence of progression)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival (OS)</measure>
    <time_frame>OS data will be collected until death, 6 months after last patient dosed, or the final DCO date, whichever is earlier.</time_frame>
    <description>OS: Time from date of treatment assignment until the date of death by any cause</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Blood concentration of durvalumab and novel oncology therapies</measure>
    <time_frame>From Cycle 1 Day 1 until Cycle 6/7 Day 1 (21-28-day cycles) depending on arm, then every 3 cycles (except for Arms A5 &amp; B5), at end of treatment (Arms A4 &amp; B4, A5 &amp; B5 only), and until 3 months following treatment discontinuation, or the final DCO date.</time_frame>
    <description>Drug concentration of durvalumab and novel oncology therapies</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Frequency of anti-drug antibodies (ADAs) for durvalumab and applicable novel oncology therapies</measure>
    <time_frame>From Cycle 1 Day 1 until Cycle 6/7 Day 1 (21-28-day cycles) depending on arm, then every 3 or 6 cycles (except for arms A5&amp;B5), at end of treatment (arms A4&amp;B4, A5&amp;B5 only), until 3/6 months after treatment discontinuation, or the final DCO date.</time_frame>
    <description>Investigation of the immunogenicity of durvalumab and each applicable novel oncology therapy in all applicable treatment arms</description>
  </secondary_outcome>
  <number_of_arms>10</number_of_arms>
  <enrollment type="Actual">175</enrollment>
  <condition>Metastatic Non-Small Cell Lung Cancer (NSCLC)</condition>
  <arm_group>
    <arm_group_label>A1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Durvalumab</description>
  </arm_group>
  <arm_group>
    <arm_group_label>A2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Durvalumab + danvatirsen</description>
  </arm_group>
  <arm_group>
    <arm_group_label>A3</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Durvalumab + oleclumab</description>
  </arm_group>
  <arm_group>
    <arm_group_label>A4</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>MEDI5752</description>
  </arm_group>
  <arm_group>
    <arm_group_label>B1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Durvalumab + Investigator's choice of chemotherapy</description>
  </arm_group>
  <arm_group>
    <arm_group_label>B2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Durvalumab + Investigator's choice of chemotherapy + danvatirsen</description>
  </arm_group>
  <arm_group>
    <arm_group_label>B3</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Durvalumab + investigator's choice of chemotherapy + oleclumab</description>
  </arm_group>
  <arm_group>
    <arm_group_label>B4</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>MEDI5752</description>
  </arm_group>
  <arm_group>
    <arm_group_label>A5</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>AZD2936</description>
  </arm_group>
  <arm_group>
    <arm_group_label>B5</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>AZD2936 + chemotherapy</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Durvalumab</intervention_name>
    <description>Durvalumab IV Cohort A: Every 4 weeks (q4w) Cohort B: Every 3 weeks (q3w) for the first 4 cycles, then every 4 weeks (q4w) starting at Cycle 5 Day 1</description>
    <arm_group_label>A1</arm_group_label>
    <arm_group_label>A2</arm_group_label>
    <arm_group_label>A3</arm_group_label>
    <arm_group_label>B1</arm_group_label>
    <arm_group_label>B2</arm_group_label>
    <arm_group_label>B3</arm_group_label>
    <other_name>MEDI4736</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Danvatirsen</intervention_name>
    <description>Danvatirsen IV Loading dose Cycle 1 Day 1, Cycle 1 Day 3, and Cycle 1 Day 5 then once a week (q1w) starting at Cycle 1 Day 8</description>
    <arm_group_label>A2</arm_group_label>
    <arm_group_label>B2</arm_group_label>
    <other_name>AZD9150</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Oleclumab</intervention_name>
    <description>Oleclumab IV Cohort A: Every 2 weeks (q2w) for first 2 cycles, then every 4 weeks (q4w) starting at Cycle 3 Day 1 Cohort B: Every 3 weeks (q3w) for the first 4 cycles, then every 4 weeks (q4w) starting at Cycle 5 Day 1</description>
    <arm_group_label>A3</arm_group_label>
    <arm_group_label>B3</arm_group_label>
    <other_name>MEDI9447</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>MEDI5752</intervention_name>
    <description>MEDI5752 IV Every 3 weeks (q3w)</description>
    <arm_group_label>A4</arm_group_label>
    <arm_group_label>B4</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Pemetrexed</intervention_name>
    <description>Pemetrexed IV Day 1 of each 21-day cycle Arm B1: Day 1 of each 21-day cycle for the first 4 cycles then either every 3 weeks (q3w) or every 4 weeks (q4w) (per investigator discretion) thereafter Arm B2 and B3: Day 1 of each 21-day cycle for the first 4 cycles then Day 1 of each 28-day cycle (q4w) thereafter Arm B5: Day 1 of each 21-day cycle throughout the study</description>
    <arm_group_label>B1</arm_group_label>
    <arm_group_label>B2</arm_group_label>
    <arm_group_label>B3</arm_group_label>
    <arm_group_label>B5</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Carboplatin</intervention_name>
    <description>Carboplatin IV Day 1 of each 21-day cycle</description>
    <arm_group_label>B1</arm_group_label>
    <arm_group_label>B2</arm_group_label>
    <arm_group_label>B3</arm_group_label>
    <arm_group_label>B5</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Gemcitabine</intervention_name>
    <description>Gemcitabine IV Days 1 and 8 of each 21-day cycle</description>
    <arm_group_label>B1</arm_group_label>
    <arm_group_label>B2</arm_group_label>
    <arm_group_label>B3</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cisplatin</intervention_name>
    <description>Cisplatin IV Day 1 of each 21-day cycle</description>
    <arm_group_label>B1</arm_group_label>
    <arm_group_label>B2</arm_group_label>
    <arm_group_label>B3</arm_group_label>
    <arm_group_label>B5</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Nab-paclitaxel</intervention_name>
    <description>Nab-paclitaxel IV Days 1, 8, and 15 of each 21-day cycle</description>
    <arm_group_label>B1</arm_group_label>
    <arm_group_label>B2</arm_group_label>
    <arm_group_label>B3</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>AZD2936</intervention_name>
    <description>AZD2936 IV</description>
    <arm_group_label>A5</arm_group_label>
    <arm_group_label>B5</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Histologically or cytologically documented Stage IV NSCLC not amenable to curative&#xD;
             surgery or radiation&#xD;
&#xD;
          -  No prior chemotherapy or any other systemic therapy for metastatic NSCLC&#xD;
&#xD;
          -  Prior platinum-containing adjuvant, neoadjuvant, or definitive chemoradiation for&#xD;
             advanced disease are eligible, if progression has occurred &gt;12 months from end of last&#xD;
             therapy&#xD;
&#xD;
          -  Known tumor PD-L1 status&#xD;
&#xD;
          -  Tumors that lack activating EGFR mutations and ALK fusions or documented local test&#xD;
             result for any other known genomic alteration for which a targeted therapy is approved&#xD;
             in first line per local standard of care&#xD;
&#xD;
          -  WHO/ECOG status at 0 or 1 at enrollment&#xD;
&#xD;
          -  Life expectancy of at least 12 weeks&#xD;
&#xD;
          -  Troponin I or T ≤ ULN (per institutional guidelines)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Active or prior documented autoimmune or inflammatory disorders&#xD;
&#xD;
          -  History of active primary immunodeficiency&#xD;
&#xD;
          -  Any prior chemotherapy or any other systemic therapy for metastatic NSCLC&#xD;
&#xD;
          -  Untreated CNS metastases&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>130 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Sandip Patel, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>UCSD Morres Cancer Center</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Chih-Hsin Yang, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>National Taiwan University Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Iowa City</city>
        <state>Iowa</state>
        <zip>52242</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <zip>15212</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37203</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Salzburg</city>
        <zip>5020</zip>
        <country>Austria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Wien</city>
        <zip>1140</zip>
        <country>Austria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Edegem</city>
        <zip>2650</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Cheongju-si</city>
        <zip>28644</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Seoul</city>
        <zip>03080</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Seoul</city>
        <zip>03722</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Seoul</city>
        <zip>05505</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Seoul</city>
        <zip>06351</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Bialystok</city>
        <zip>15-027</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Bydgoszcz</city>
        <zip>85-796</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Gdańsk</city>
        <zip>80-214</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Grudziądz</city>
        <zip>86-300</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Olsztyn</city>
        <zip>10-357</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Tomaszów Mazowiecki</city>
        <zip>97-200</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Warszawa</city>
        <zip>02-781</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Wroclaw</city>
        <zip>53-413</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Łódź</city>
        <zip>90-302</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Krasnoyarsk</city>
        <zip>660133</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Moscow</city>
        <zip>115478</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Saint Petersburg</city>
        <zip>197758</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Sankt-Peterburg</city>
        <zip>197758</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>St.Petersburg</city>
        <zip>191014</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Barcelona</city>
        <zip>08025</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Barcelona</city>
        <zip>08035</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Barcelona</city>
        <zip>8003</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Madrid</city>
        <zip>28034</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Madrid</city>
        <zip>28041</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Sevilla</city>
        <zip>41013</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Kaohsiung</city>
        <zip>807</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Taichung City</city>
        <zip>402</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Taichung</city>
        <zip>40705</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Tainan City</city>
        <zip>70403</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Taipei</city>
        <zip>10002</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Taipei</city>
        <zip>112</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Taipei</city>
        <zip>235</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Taoyuan</city>
        <zip>333</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Bangkok</city>
        <zip>10330</zip>
        <country>Thailand</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Bangkok</city>
        <zip>10700</zip>
        <country>Thailand</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Chiang Mai</city>
        <zip>50200</zip>
        <country>Thailand</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Hat Yai</city>
        <zip>90110</zip>
        <country>Thailand</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Austria</country>
    <country>Belgium</country>
    <country>Korea, Republic of</country>
    <country>Poland</country>
    <country>Russian Federation</country>
    <country>Spain</country>
    <country>Taiwan</country>
    <country>Thailand</country>
    <country>United States</country>
  </location_countries>
  <removed_countries>
    <country>Bulgaria</country>
    <country>Canada</country>
    <country>Hong Kong</country>
    <country>Netherlands</country>
  </removed_countries>
  <verification_date>May 2023</verification_date>
  <study_first_submitted>December 13, 2018</study_first_submitted>
  <study_first_submitted_qc>January 24, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 28, 2019</study_first_posted>
  <last_update_submitted>May 29, 2023</last_update_submitted>
  <last_update_submitted_qc>May 29, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">June 1, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>First-Line Stage IV Metastatic Non-Small Cell Lung Cancer</keyword>
  <keyword>Stage IV Metastatic Non-Small Cell Lung Cancer</keyword>
  <keyword>Metastatic Non-Small Cell Lung Cancer</keyword>
  <keyword>Non-Small Cell Lung Cancer</keyword>
  <keyword>Non-Small Cell Lung</keyword>
  <keyword>Non-Small Cell</keyword>
  <keyword>NSCLC</keyword>
  <keyword>Non-Small Cell Lung Carcinoma</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>Paclitaxel</mesh_term>
    <mesh_term>Carboplatin</mesh_term>
    <mesh_term>Gemcitabine</mesh_term>
    <mesh_term>Pemetrexed</mesh_term>
    <mesh_term>Durvalumab</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_time_frame>AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.</ipd_time_frame>
    <ipd_access_criteria>When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.</ipd_access_criteria>
    <ipd_url>https://astrazenecagroup-dt.pharmacm.com/DT/Home</ipd_url>
  </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/NCT03819465
org study id: D933IC00001
secondary id: 2018-001748-74
nct id: NCT03819465
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
This study is designed to determine the efficacy and safety of durvalumab and/or novel
      oncology therapies, with or without chemotherapy, for first-line Stage IV Non-Small Cell Lung
      Cancer (NSCLC)
This is a Phase IB, Open-Label, Multi-Center Study to Determine the Efficacy and Safety of
      Durvalumab and/or Novel Oncology Therapies, With or Without Chemotherapy, for First-Line
      Stage IV Non-Small Cell Lung Cancer (NSCLC).
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Treatment arms for MEDI5752 (Arms A4 and B4) will enroll 42 and 60 patients, respectively. Arm B5 (AZD2936+chemotherapy) will enroll 60 patients.
For all other treatment arms, 30 patients will be enrolled into each arm; additional patients may be enrolled in order to have 30 evaluable patients per arm (ie, dosed).
primary purpose: Treatment
masking: None (Open Label)
measure: Assessment of AEs by CTCAE v5.0
time frame: From informed consent until the safety follow-up visit 3 months after the last dose of study drug, or until the final data cut-off (DCO) date, whichever is earlier.
description: Assessment of safety and tolerability of each treatment arm
measure: Objective Response Rate (ORR)
time frame: Tumor assessments every 6-9 weeks until week 48-54, then every 12 or 18 weeks, depending on treatment arm until the earliest of radiological progression, death, withdrawal of consent, or final DCO (approximately 4 months after last patient randomized).
description: Assessment of the efficacy of each treatment arm according to RECIST 1.1. ORR: The percentage of evaluable patients with a confirmed Investigator-assessed visit response of CR or PR
measure: Duration of Response (DoR)
time frame: Tumor assessments every 6-9 weeks until week 48-54, then every 12 or 18 weeks, depending on treatment arm until the earliest of radiological progression, death, withdrawal of consent, or final DCO (approximately 4 months after last patient randomized).
description: Assessment of the efficacy of each treatment arm according to RECIST 1.1. DoR: Time from date of first detection of objective response until the date of objective radiological disease progression
measure: Progression Free Survival (PFS)
time frame: Tumor assessments every 6-9 weeks until week 48-54, then every 12/18 weeks based on arm until progression, death, withdrawal or final DCO. Further PFS data will be collected until 6 months after last patient dosed or final DCO
description: Assessment of the efficacy of each treatment arm according to RECIST 1.1. PFS: Time from date of treatment assignment until the date of objective radiological disease progression using RECIST 1.1 or death (by any cause in the absence of progression)
measure: Overall Survival (OS)
time frame: OS data will be collected until death, 6 months after last patient dosed, or the final DCO date, whichever is earlier.
description: OS: Time from date of treatment assignment until the date of death by any cause
measure: Blood concentration of durvalumab and novel oncology therapies
time frame: From Cycle 1 Day 1 until Cycle 6/7 Day 1 (21-28-day cycles) depending on arm, then every 3 cycles (except for Arms A5 & B5), at end of treatment (Arms A4 & B4, A5 & B5 only), and until 3 months following treatment discontinuation, or the final DCO date.
description: Drug concentration of durvalumab and novel oncology therapies
measure: Frequency of anti-drug antibodies (ADAs) for durvalumab and applicable novel oncology therapies
time frame: From Cycle 1 Day 1 until Cycle 6/7 Day 1 (21-28-day cycles) depending on arm, then every 3 or 6 cycles (except for arms A5&B5), at end of treatment (arms A4&B4, A5&B5 only), until 3/6 months after treatment discontinuation, or the final DCO date.
description: Investigation of the immunogenicity of durvalumab and each applicable novel oncology therapy in all applicable treatment arms
arm group label: A1
arm group type: Experimental
description: Durvalumab
arm group label: A2
arm group type: Experimental
description: Durvalumab + danvatirsen
arm group label: A3
arm group type: Experimental
description: Durvalumab + oleclumab
arm group label: A4
arm group type: Experimental
description: MEDI5752
arm group label: B1
arm group type: Experimental
description: Durvalumab + Investigator's choice of chemotherapy
arm group label: B2
arm group type: Experimental
description: Durvalumab + Investigator's choice of chemotherapy + danvatirsen
arm group label: B3
arm group type: Experimental
description: Durvalumab + investigator's choice of chemotherapy + oleclumab
arm group label: B4
arm group type: Experimental
description: MEDI5752
arm group label: A5
arm group type: Experimental
description: AZD2936
arm group label: B5
arm group type: Experimental
description: AZD2936 + chemotherapy
intervention type: Drug
intervention name: Durvalumab
description: Durvalumab IV Cohort A: Every 4 weeks (q4w) Cohort B: Every 3 weeks (q3w) for the first 4 cycles, then every 4 weeks (q4w) starting at Cycle 5 Day 1
arm group label: A1
arm group label: A2
arm group label: A3
arm group label: B1
arm group label: B2
arm group label: B3
other name: MEDI4736
intervention type: Drug
intervention name: Danvatirsen
description: Danvatirsen IV Loading dose Cycle 1 Day 1, Cycle 1 Day 3, and Cycle 1 Day 5 then once a week (q1w) starting at Cycle 1 Day 8
arm group label: A2
arm group label: B2
other name: AZD9150
intervention type: Drug
intervention name: Oleclumab
description: Oleclumab IV Cohort A: Every 2 weeks (q2w) for first 2 cycles, then every 4 weeks (q4w) starting at Cycle 3 Day 1 Cohort B: Every 3 weeks (q3w) for the first 4 cycles, then every 4 weeks (q4w) starting at Cycle 5 Day 1
arm group label: A3
arm group label: B3
other name: MEDI9447
intervention type: Drug
intervention name: MEDI5752
description: MEDI5752 IV Every 3 weeks (q3w)
arm group label: A4
arm group label: B4
intervention type: Drug
intervention name: Pemetrexed
description: Pemetrexed IV Day 1 of each 21-day cycle Arm B1: Day 1 of each 21-day cycle for the first 4 cycles then either every 3 weeks (q3w) or every 4 weeks (q4w) (per investigator discretion) thereafter Arm B2 and B3: Day 1 of each 21-day cycle for the first 4 cycles then Day 1 of each 28-day cycle (q4w) thereafter Arm B5: Day 1 of each 21-day cycle throughout the study
arm group label: B1
arm group label: B2
arm group label: B3
arm group label: B5
intervention type: Drug
intervention name: Carboplatin
description: Carboplatin IV Day 1 of each 21-day cycle
arm group label: B1
arm group label: B2
arm group label: B3
arm group label: B5
intervention type: Drug
intervention name: Gemcitabine
description: Gemcitabine IV Days 1 and 8 of each 21-day cycle
arm group label: B1
arm group label: B2
arm group label: B3
intervention type: Drug
intervention name: Cisplatin
description: Cisplatin IV Day 1 of each 21-day cycle
arm group label: B1
arm group label: B2
arm group label: B3
arm group label: B5
intervention type: Drug
intervention name: Nab-paclitaxel
description: Nab-paclitaxel IV Days 1, 8, and 15 of each 21-day cycle
arm group label: B1
arm group label: B2
arm group label: B3
intervention type: Drug
intervention name: AZD2936
description: AZD2936 IV
arm group label: A5
arm group label: B5
criteria: 
gender: All
minimum age: 18 Years
maximum age: 130 Years
healthy volunteers: No
last name: Sandip Patel, MD
role: Principal Investigator
affiliation: UCSD Morres Cancer Center
last name: Chih-Hsin Yang, MD
role: Principal Investigator
affiliation: National Taiwan University Hospital
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country: Austria
country: Belgium
country: Korea, Republic of
country: Poland
country: Russian Federation
country: Spain
country: Taiwan
country: Thailand
country: United States
country: Bulgaria
country: Canada
country: Hong Kong
country: Netherlands
responsible party type: Sponsor
mesh term: Lung Neoplasms
mesh term: Carcinoma, Non-Small-Cell Lung
mesh term: Paclitaxel
mesh term: Carboplatin
mesh term: Gemcitabine
mesh term: Pemetrexed
mesh term: Durvalumab
sharing ipd: Yes
ipd description: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd time frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
ipd access criteria: When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
ipd url: https://astrazenecagroup-dt.pharmacm.com/DT/Home