<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/NCT02978482</url>
  </required_header>
  <id_info>
    <org_study_id>D419AC00006</org_study_id>
    <nct_id>NCT02978482</nct_id>
  </id_info>
  <brief_title>A Phase 1/2 Study of Durvalumab(MEDI4736) and Tremelimumab in Chinese Patients With Advanced Malignancies</brief_title>
  <official_title>A Phase 1/2 Open-label, Multi-center Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Anti-tumor Activity of Durvalumab (MEDI4736) in Combination With Tremelimumab in Chinese Patients With Advanced Malignancies</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>
  </oversight_info>
  <brief_summary>
    <textblock>
      A Phase 1/2 Open-label, Multi-center Study to Evaluate the Safety, Tolerability,&#xD;
      Pharmacokinetics, and Anti-tumor Activity of Durvalumab (MEDI4736) in combination with&#xD;
      tremelimumab in Chinese Patients with Advanced Malignancies&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 1, 2016</start_date>
  <completion_date type="Actual">November 26, 2020</completion_date>
  <primary_completion_date type="Actual">January 28, 2018</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Maximum plasma concentration (Cmax)</measure>
    <time_frame>approximately 6 months after the last evaluable patient in Phase 1 portion is first dosed</time_frame>
    <description>Only for phase 1 portion of the study</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Trough plasma concentration (Ctrough)</measure>
    <time_frame>approximately 6 months after the last evaluable patient is first dosed in phase 1 portion</time_frame>
    <description>Only for phase 1 portion of the study</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Area under the plasma drug concentration-time curve from time zero to Day 28 post-dose (AUC 0-28)</measure>
    <time_frame>approximately 6 months after the last evaluable patient is first dosed in phase 1 portion</time_frame>
    <description>Only for phase 1 portion of the study</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Adverse event</measure>
    <time_frame>Approximately 12 months after the last evaluable patient from Ph 1 is 1st dosed or the last patient has withdrawn from study or the study discontinued by Sponsor</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Objective response rate (ORR)</measure>
    <time_frame>Approximately 12 months after the last evaluable patient is dosed, or the last patient has withdrawn from the study or the study is discontinued by the sponsor.</time_frame>
    <description>Only for phase 2 portion of the study (Phase 2 part withdrawn without initiation)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Anti-drug antibody (ADA)</measure>
    <time_frame>approximately 12 months after the last evaluable patient is first dosed, or the last patient has withdrawn from the study, or the study is discontinued by the Sponsor</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Anti-drug antibody neutralizing antibodies (ADA nAB)</measure>
    <time_frame>approximately 12 months after the last evaluable patient is first dosed, or the last patient has withdrawn from the study, or the study is discontinued by the Sponsor</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Complete response/Partial response/Stable disease/Progressive disease</measure>
    <time_frame>approximately 6 months after the last evaluable patient is first dosed in phase 1 portion</time_frame>
    <description>Only for phase 1 portion of the study</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival (OS)</measure>
    <time_frame>approximately 12 months after the last evaluable patient is first dosed, or the last patient has withdrawn from the study, or the study is discontinued by the Sponsor</time_frame>
    <description>Only for phase 2 portion of the study (Phase 2 part withdrawn without initiation)</description>
  </secondary_outcome>
  <other_outcome>
    <measure>PD-L1 status</measure>
    <time_frame>through study completion, an average of 2 years</time_frame>
    <description>Only for phase 2 portion of the study (Phase 2 part withdrawn without initiation)</description>
  </other_outcome>
  <other_outcome>
    <measure>CD8+ T cells</measure>
    <time_frame>through study completion, an average of 2 years</time_frame>
    <description>Only for phase 2 portion of the study (Phase 2 part withdrawn without initiation)</description>
  </other_outcome>
  <other_outcome>
    <measure>IFNγ</measure>
    <time_frame>through study completion, an average of 2 years</time_frame>
    <description>Only for phase 2 portion of the study (Phase 2 part withdrawn without initiation)</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">26</enrollment>
  <condition>Advanced Malignancy</condition>
  <arm_group>
    <arm_group_label>durvalumab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>durvalumab alone</description>
  </arm_group>
  <arm_group>
    <arm_group_label>durvalumab+tremelimumab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>durvalumab plus tremelimumab</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>durvalumab</intervention_name>
    <description>durvalumab (MEDI4736) 20mg/kg via IV infusion every 4 weeks until confirmed disease progression or unacceptable toxicity</description>
    <arm_group_label>durvalumab</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>tremelimumab + durvalumab</intervention_name>
    <description>20 mg/kg durvalumab (MEDI4736) via IV infusion q4w and 1 mg/kg tremelimumab via IV infusion q4w for up to 4 doses/cycles, and then continue 20 mg/kg durvalumab (MEDI4736) q4w starting on Week 16 for up to confirmed disease progression</description>
    <arm_group_label>durvalumab+tremelimumab</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Provision of informed consent prior to any study specific procedures&#xD;
&#xD;
          -  Male or female, aged at least 18 years&#xD;
&#xD;
          -  For Phase 1 PK cohort:&#xD;
&#xD;
        Patients with histologically or cytologically confirmed advanced and/or metastatic solid&#xD;
        tumors other than HCC refractory or intolerable to existing standard of treatment&#xD;
&#xD;
        For Phase 2 cohort:&#xD;
&#xD;
        For nasopharyngeal carcinoma:&#xD;
&#xD;
        Patients with histologically or cytologically confirmed nasopharyngeal carcinoma must have&#xD;
        locally advanced or metastatic disease progressed on or after at least 1 chemotherapy&#xD;
        regimen with or without radiotherapy.&#xD;
&#xD;
          -  ONLY FOR PHASE 2 PORTION: mandatory tumor sample&#xD;
&#xD;
          -  No prior exposure to immune-mediated therapy including, but not limited to, other anti&#xD;
             CTLA-4, anti-PD-1, anti-PD-L1, and anti-programmed cell death ligand 2 (anti-PD-L2)&#xD;
             antibodies, excluding therapeutic anticancer vaccines.&#xD;
&#xD;
          -  Life expectancy ≥12 weeks at Day 1&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1&#xD;
&#xD;
          -  At least 1 lesion that can be accurately measured at baseline, and that is suitable&#xD;
             for repeated measurements as per RECIST 1.1 guidelines.&#xD;
&#xD;
          -  Adequate organ and marrow function&#xD;
&#xD;
          -  Hemoglobin ≥9 g/dL Absolute neutrophil count ≥1.0 × 109 /L Platelet count ≥75 × 109/L&#xD;
             Total serum bilirubin ≤1.5×upper limit of normal (ULN) ALT and AST ≤2.5×ULN; for&#xD;
             patients with hepatic metastases, ALT and AST ≤5×ULN Calculated creatinine clearance&#xD;
             &gt;40 mL/min as determined by Cockcroft-Gault (using actual body weight), or by measured&#xD;
             24-hour urine collection for determination of creatinine clearance.&#xD;
&#xD;
          -  Evidence of post-menopausal status, or negative urinary or serum pregnancy test for&#xD;
             female pre-menopausal patients.&#xD;
&#xD;
          -  Exclusion Criteria:&#xD;
&#xD;
          -  Any concurrent chemotherapy, IP, biologic, or hormonal therapy for cancer treatment.&#xD;
             Concurrent use of hormonal therapy for non-cancer-related conditions (eg, hormone&#xD;
             replacement therapy) is acceptable. Note: Local treatment of isolated lesions for&#xD;
             palliative intent is acceptable (eg, local surgery or radiotherapy).&#xD;
&#xD;
          -  Receipt of last dose of an approved (marketed) anticancer therapy (chemotherapy,&#xD;
             targeted therapy, biologic therapy, mAbs, etc) within 21 days prior to the first dose&#xD;
             of study treatment. If sufficient washout time has not occurred due to the schedule or&#xD;
             PK properties of an agent, a longer washout period will be required, as agreed upon by&#xD;
             AstraZeneca and the Investigator.&#xD;
&#xD;
          -  Radiotherapy treatment to more than 30% of the bone marrow or with a wide field of&#xD;
             radiation within 4 weeks of the first dose of study drug.&#xD;
&#xD;
          -  Major surgical procedure (as defined by the Investigator) within 28 days prior to the&#xD;
             first dose of IP. Note: Local surgery of isolated lesions for palliative intent is&#xD;
             acceptable.&#xD;
&#xD;
          -  History of allogenic organ transplantation&#xD;
&#xD;
          -  Any unresolved toxicity National Cancer Institute (NCI) CTCAE Version 4.03 Grade ≥2&#xD;
             from previous anticancer therapy&#xD;
&#xD;
          -  Active or prior documented autoimmune or inflammatory disorders (including&#xD;
             inflammatory bowel disease [eg, colitis or Crohn's disease], diverticulitis [with the&#xD;
             exception of diverticulosis], celiac disease, systemic lupus erythematosus,&#xD;
             Sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis], Graves'&#xD;
             disease, rheumatoid arthritis, hypophysitis, uveitis, etc).&#xD;
&#xD;
          -  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, serious chronic&#xD;
             gastrointestinal conditions associated with diarrhea, or psychiatric illness/social&#xD;
             situations that would limit compliance with study requirement, substantially increase&#xD;
             risk of incurring AEs or compromise the ability of the patient to give written&#xD;
             informed consent&#xD;
&#xD;
          -  History of another primary malignancy&#xD;
&#xD;
          -  History of leptomeningeal carcinomatosis&#xD;
&#xD;
          -  Brain metastases or spinal cord compression unless asymptomatic or treated and stable&#xD;
             off steroids and anti-convulsants for at least 14 days prior to study treatment.&#xD;
&#xD;
          -  QT interval corrected for heart rate using Fridericia's formula (QTcF) ≥470 ms&#xD;
             calculated.&#xD;
&#xD;
          -  History of active primary immunodeficiency&#xD;
&#xD;
          -  Active infection including tuberculosis, hepatitis B, hepatitis C, or human&#xD;
             immunodeficiency virus .&#xD;
&#xD;
          -  Current or prior use of immunosuppressive medication within 14 days before the first&#xD;
             dose of durvalumab (MEDI4736) or tremelimumab.&#xD;
&#xD;
          -  Receipt of live, attenuated vaccine within 30 days prior to the first dose of IP.&#xD;
&#xD;
          -  Female patients who are pregnant or breast-feeding or male or female patients of&#xD;
             reproductive potential who are not willing to employ effective birth control from&#xD;
             screening to 180 days after the last dose of durvalumab (MEDI4736) plus tremelimumab&#xD;
             combination therapy or 90 days after the last dose of durvalumab (MEDI4736)&#xD;
             monotherapy.&#xD;
&#xD;
          -  Known allergy or hypersensitivity to IP or any IP excipient, or to other humanized&#xD;
             mAbs&#xD;
&#xD;
          -  Prior randomisation or treatment in a previous durvalumab (MEDI4736) and/or&#xD;
             tremelimumab clinical study regardless of treatment arm assignment&#xD;
&#xD;
          -  NSCLC patients have history of interstitial lung disease&#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>Lin Shen</last_name>
    <role>Principal Investigator</role>
    <affiliation>Peking University Cancer Hospital &amp; Institute</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Urban Scheuring</last_name>
    <role>Study Director</role>
    <affiliation>AstraZeneca GMD IO, Melbourn Science Park, Melbourn, Royston, Hertfordshire, SG8 6HB, UK</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Changchun</city>
        <zip>130000</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Changchun</city>
        <zip>130012</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <link>
    <url>https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Search</url>
    <description>Results of this clinical trial are available on www.astrazenecaclinicaltrials.com</description>
  </link>
  <verification_date>August 2021</verification_date>
  <study_first_submitted>November 8, 2016</study_first_submitted>
  <study_first_submitted_qc>November 28, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 1, 2016</study_first_posted>
  <last_update_submitted>August 12, 2021</last_update_submitted>
  <last_update_submitted_qc>August 12, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">August 18, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Neoplasms</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>
    <mesh_term>Antibodies, Monoclonal</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 request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.</ipd_description>
    <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/NCT02978482
org study id: D419AC00006
nct id: NCT02978482
lead sponsor: 
has dmc: No
A Phase 1/2 Open-label, Multi-center Study to Evaluate the Safety, Tolerability,
      Pharmacokinetics, and Anti-tumor Activity of Durvalumab (MEDI4736) in combination with
      tremelimumab in Chinese Patients with Advanced Malignancies
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Maximum plasma concentration (Cmax)
time frame: approximately 6 months after the last evaluable patient in Phase 1 portion is first dosed
description: Only for phase 1 portion of the study
measure: Trough plasma concentration (Ctrough)
time frame: approximately 6 months after the last evaluable patient is first dosed in phase 1 portion
description: Only for phase 1 portion of the study
measure: Area under the plasma drug concentration-time curve from time zero to Day 28 post-dose (AUC 0-28)
time frame: approximately 6 months after the last evaluable patient is first dosed in phase 1 portion
description: Only for phase 1 portion of the study
measure: Adverse event
time frame: Approximately 12 months after the last evaluable patient from Ph 1 is 1st dosed or the last patient has withdrawn from study or the study discontinued by Sponsor
measure: Objective response rate (ORR)
time frame: Approximately 12 months after the last evaluable patient is dosed, or the last patient has withdrawn from the study or the study is discontinued by the sponsor.
description: Only for phase 2 portion of the study (Phase 2 part withdrawn without initiation)
measure: Anti-drug antibody (ADA)
time frame: approximately 12 months after the last evaluable patient is first dosed, or the last patient has withdrawn from the study, or the study is discontinued by the Sponsor
measure: Anti-drug antibody neutralizing antibodies (ADA nAB)
time frame: approximately 12 months after the last evaluable patient is first dosed, or the last patient has withdrawn from the study, or the study is discontinued by the Sponsor
measure: Complete response/Partial response/Stable disease/Progressive disease
time frame: approximately 6 months after the last evaluable patient is first dosed in phase 1 portion
description: Only for phase 1 portion of the study
measure: Overall survival (OS)
time frame: approximately 12 months after the last evaluable patient is first dosed, or the last patient has withdrawn from the study, or the study is discontinued by the Sponsor
description: Only for phase 2 portion of the study (Phase 2 part withdrawn without initiation)
measure: PD-L1 status
time frame: through study completion, an average of 2 years
description: Only for phase 2 portion of the study (Phase 2 part withdrawn without initiation)
measure: CD8+ T cells
time frame: through study completion, an average of 2 years
description: Only for phase 2 portion of the study (Phase 2 part withdrawn without initiation)
measure: IFNγ
time frame: through study completion, an average of 2 years
description: Only for phase 2 portion of the study (Phase 2 part withdrawn without initiation)
arm group label: durvalumab
arm group type: Experimental
description: durvalumab alone
arm group label: durvalumab+tremelimumab
arm group type: Experimental
description: durvalumab plus tremelimumab
intervention type: Drug
intervention name: durvalumab
description: durvalumab (MEDI4736) 20mg/kg via IV infusion every 4 weeks until confirmed disease progression or unacceptable toxicity
arm group label: durvalumab
intervention type: Drug
intervention name: tremelimumab + durvalumab
description: 20 mg/kg durvalumab (MEDI4736) via IV infusion q4w and 1 mg/kg tremelimumab via IV infusion q4w for up to 4 doses/cycles, and then continue 20 mg/kg durvalumab (MEDI4736) q4w starting on Week 16 for up to confirmed disease progression
arm group label: durvalumab+tremelimumab
criteria: 
gender: All
minimum age: 18 Years
maximum age: 130 Years
healthy volunteers: No
last name: Lin Shen
role: Principal Investigator
affiliation: Peking University Cancer Hospital & Institute
last name: Urban Scheuring
role: Study Director
affiliation: AstraZeneca GMD IO, Melbourn Science Park, Melbourn, Royston, Hertfordshire, SG8 6HB, UK
facility: 
facility: 
country: China
url: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Search
description: Results of this clinical trial are available on www.astrazenecaclinicaltrials.com
responsible party type: Sponsor
mesh term: Neoplasms
mesh term: Durvalumab
mesh term: Tremelimumab
mesh term: Antibodies, Monoclonal
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 request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
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