<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/NCT03260504</url>
  </required_header>
  <id_info>
    <org_study_id>9611</org_study_id>
    <secondary_id>NCI-2017-01416</secondary_id>
    <secondary_id>RG1717068</secondary_id>
    <nct_id>NCT03260504</nct_id>
  </id_info>
  <brief_title>Aldesleukin and Pembrolizumab in Treating Patients With Advanced or Metastatic Kidney Cancer</brief_title>
  <official_title>A Phase I Trial of Interleukin-2 (Aldesleukin) and Pembrolizumab Combination Therapy for Patients With Advanced Renal Cell Carcinoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Washington</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Merck Sharp &amp; Dohme LLC</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Prometheus Laboratories</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Washington</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>
      This phase I trial studies the side effects and best dose of aldesleukin when given together&#xD;
      with pembrolizumab in treating patients with kidney cancer that has spread to other parts of&#xD;
      the body. Aldesleukin may stimulate white blood cells to kill kidney cancer cells.&#xD;
      Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune&#xD;
      system attack the cancer, and may interfere with the ability of tumor cells to avoid&#xD;
      recognition by immune cells. Giving aldesleukin and pembrolizumab may work better in treating&#xD;
      patients with kidney cancer.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      OUTLINE: This is a dose-escalation study of aldesleukin.&#xD;
&#xD;
      Patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1. Patients also&#xD;
      receive aldesleukin subcutaneously (SC) 5 days per week for 6 weeks; or aldesleukin IV on&#xD;
      days 2-6 of pembrolizumab cycles 1 and 2. Pembrolizumab treatment repeats every 3 weeks for 4&#xD;
      cycles per treatment course in the absence of clinical disease progression or unacceptable&#xD;
      toxicity.&#xD;
&#xD;
      After completion of study treatment, patients are followed up via surveillance scans for&#xD;
      every 3 months for up to 1 year or until disease progression.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Insufficient funding&#xD;
  </why_stopped>
  <start_date type="Actual">August 28, 2018</start_date>
  <completion_date type="Actual">July 26, 2022</completion_date>
  <primary_completion_date type="Actual">July 26, 2022</primary_completion_date>
  <phase>Phase 1</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>Incidence of adverse events</measure>
    <time_frame>Duration of study participation and Surveillance Follow up.</time_frame>
    <description>Assessed by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version (v) 5.0.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Anti-tumor activity</measure>
    <time_frame>At baseline and every 3 months</time_frame>
    <description>Tumor imaging post-treatment compared to baseline imaging; assessed by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall response rate (ORR)</measure>
    <time_frame>At baseline and every 3 months</time_frame>
    <description>Assessed by RECIST 1.1</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Disease control rate (DCR)</measure>
    <time_frame>At baseline and every 3 months</time_frame>
    <description>Assessed by RECIST 1.1.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression free survival (PFS)</measure>
    <time_frame>At baseline and every 3 months</time_frame>
    <description>PFS will be evaluated using the method of Kaplan-Meier. Median PFS times and associated 95% confidence interval will also be calculated</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in performance status</measure>
    <time_frame>Duration of study participation and Surveillance Follow up.</time_frame>
    <description>Assessed by Eastern Cooperative Oncology Group (ECOG) Performance Scale</description>
  </secondary_outcome>
  <other_outcome>
    <measure>PD-L1 expression</measure>
    <time_frame>Retrospective after completion of enrollment</time_frame>
    <description>Will be assessed by immunohistochemistry.</description>
  </other_outcome>
  <other_outcome>
    <measure>Absolute numbers of regulatory T cells (Treg)</measure>
    <time_frame>Retrospective after completion of enrollment</time_frame>
    <description>Will assess the ratio of Treg and effector T cells. Analyses of T cell subsets will be correlated with clinical outcomes.</description>
  </other_outcome>
  <other_outcome>
    <measure>Absolute numbers of effector T cells (Teff)</measure>
    <time_frame>Retrospective after completion of enrollment</time_frame>
    <description>Will assess the ratio of Treg and Teff. Analyses of T cell subsets will be correlated with clinical outcomes.</description>
  </other_outcome>
  <other_outcome>
    <measure>De novo 5T4 specific humoral and/or cellular immune responses</measure>
    <time_frame>Retrospective after completion of enrollment</time_frame>
    <description>Will be analyzed as a potential marker of &quot;on target&quot; effective anti-tumor immunity and correlated with clinical response.</description>
  </other_outcome>
  <other_outcome>
    <measure>Tumor infiltrating lymphocytes (TIL) clonality score</measure>
    <time_frame>Retrospective after completion of enrollment</time_frame>
    <description>TIL clonality score will be correlated with clinical outcomes of renal cell carcinoma (RCC) patients treated with IL-2 plus pembrolizumab.</description>
  </other_outcome>
  <other_outcome>
    <measure>Chromosomal copy number alterations</measure>
    <time_frame>Retrospective after completion of enrollment</time_frame>
    <description>OncoScan chromosomal array analyses will be carried out on archived tumor for RCC patients treated with IL-2 and pembrolizumab and chromosomal numerical abnormalities (CNAs) correlated to objective response rate.</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">6</enrollment>
  <condition>Advanced Clear Cell Renal Cell Carcinoma</condition>
  <condition>Stage III Renal Cell Cancer</condition>
  <condition>Stage IV Renal Cell Cancer</condition>
  <condition>Metastatic Clear Cell Renal Cell Carcinoma</condition>
  <arm_group>
    <arm_group_label>Treatment (pembrolizumab, aldesleukin)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1. Patients also receive aldesleukin subcutaneously (SC) 5 days per week for 6 weeks; or aldesleukin IV on days 2-6 of pembrolizumab cycles 1 and 2. Pembrolizumab treatment repeats every 3 weeks for 4 cycles per treatment course in the absence of clinical disease progression or unacceptable toxicity.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Aldesleukin</intervention_name>
    <description>Given SC or IV</description>
    <arm_group_label>Treatment (pembrolizumab, aldesleukin)</arm_group_label>
    <other_name>125-L-Serine-2-133-interleukin 2</other_name>
    <other_name>Proleukin</other_name>
    <other_name>r-serHuIL-2</other_name>
    <other_name>Recombinant Human IL-2</other_name>
    <other_name>Recombinant Human Interleukin-2</other_name>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Pembrolizumab</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Treatment (pembrolizumab, aldesleukin)</arm_group_label>
    <other_name>Keytruda</other_name>
    <other_name>Lambrolizumab</other_name>
    <other_name>MK-3475</other_name>
    <other_name>SCH 900475</other_name>
    <other_name>Immunoglobulin G4</other_name>
    <other_name>Anti-(Human Programmed Cell Death 1)</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Be willing and able to provide written informed consent for the trial&#xD;
&#xD;
          -  Be &gt;= 18 years of age on day of signing informed consent&#xD;
&#xD;
          -  Have histologic confirmation of RCC with a clear cell component&#xD;
&#xD;
          -  Have advanced (not amenable to potentially curative surgery) or metastatic RCC&#xD;
&#xD;
          -  May have received previous systemic treatments or regimens for metastatic RCC. Prior&#xD;
             therapy can include checkpoint blocking antibodies targeting PD-1, PD-L1, or cytotoxic&#xD;
             Tlymphocyte-associated antigen-4 (CTLA-4) and/or targeted agents including TKIs, mTOR&#xD;
             inhibitors, or bevacizumab. Patients may choose to receive study treatment as their&#xD;
             initial therapy&#xD;
&#xD;
          -  Previously treated patients must have documented disease progression after their last&#xD;
             line of therapy&#xD;
&#xD;
          -  Have measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST)&#xD;
             1.1&#xD;
&#xD;
          -  Available tissue from an archival tissue sample or newly obtained core or excisional&#xD;
             biopsy of a tumor lesion&#xD;
&#xD;
          -  Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG)&#xD;
             performance scale&#xD;
&#xD;
          -  Absolute neutrophil count (ANC) &gt;= 1,500 /mcL (within 14 days of treatment initiation)&#xD;
&#xD;
          -  Platelets &gt;= 100,000/mcL (within 14 days of treatment initiation)&#xD;
&#xD;
          -  Hemoglobin &gt;= 9 g/dL or &gt;= 5.6 mmol/L (within 14 days of treatment initiation)&#xD;
&#xD;
          -  Serum creatinine =&lt; 1.5 X upper limit of normal (ULN) OR measured or calculated&#xD;
             creatinine clearance (glomerular filtration rate [GFR] can also be used in place of&#xD;
             creatinine or CrCl) &gt;= 40 mL/min for subject with creatinine levels &gt; 1.5 X&#xD;
             institutional ULN; creatinine clearance should be calculated by Cockcroft-Gault&#xD;
             (within 14 days of treatment initiation)&#xD;
&#xD;
          -  Serum total bilirubin =&lt; 1.5 X ULN OR direct bilirubin =&lt; ULN for subjects with total&#xD;
             bilirubin levels &gt; 1.5 ULN (within 14 days of treatment initiation)&#xD;
&#xD;
          -  Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and&#xD;
             alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) =&lt; 2.5 X&#xD;
             ULN OR =&lt; 5 X ULN for subjects with liver metastases (within 14 days of treatment&#xD;
             initiation)&#xD;
&#xD;
          -  International normalized ratio (INR) or prothrombin time (PT) =&lt; 1.5 X ULN unless&#xD;
             subject is receiving anticoagulant therapy as long as PT or partial thromboplastin&#xD;
             time (PTT) is within therapeutic range of intended use of anticoagulants (dose level 2&#xD;
             and 3 patients only) (within 14 days of treatment initiation)&#xD;
&#xD;
          -  Activated partial thromboplastin time (aPTT) =&lt; 1.5 X ULN unless subject is receiving&#xD;
             anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use&#xD;
             of anticoagulants (dose level 2 and 3 patients only) (within 14 days of treatment&#xD;
             initiation)&#xD;
&#xD;
          -  Forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) &gt;= 65% of&#xD;
             predicted (Testing performed prior to study screening are allowable. Pre-treatment&#xD;
             testing must have been completed within 6 months of start of treatment) (within 14&#xD;
             days of treatment initiation)&#xD;
&#xD;
          -  Left ventricular ejection fraction (LVEF) &gt;= 50% measured by multigated acquisition&#xD;
             (MUGA) scan, echo, or stress test study with myocardial perfusion imaging (Testing&#xD;
             performed prior to study screening are allowable. Pre-treatment testing must have been&#xD;
             completed within 6 months of start of treatment) (within 14 days of treatment&#xD;
             initiation)&#xD;
&#xD;
          -  Normal/negative cardiac stress testing with myocardial perfusion imaging OR cardiac&#xD;
             catheterization with non-significant angiogram findings reviewed by a cardiology&#xD;
             consultant (Testing performed prior to study screening are allowable. Pre-treatment&#xD;
             testing must have been completed within 6 months of start of treatment) (within 14&#xD;
             days of treatment initiation)&#xD;
&#xD;
          -  Female subject of childbearing potential should have a negative urine or serum&#xD;
             pregnancy test within 72 hours prior to receiving the first dose of study medication;&#xD;
             if the urine test is positive or cannot be confirmed as negative, a serum pregnancy&#xD;
             test will be required&#xD;
&#xD;
          -  Female subjects of childbearing potential should be willing to use 2 methods of birth&#xD;
             control or be surgically sterile, or abstain from heterosexual activity for the course&#xD;
             of the study through 140 days after the last dose of study medication; subjects of&#xD;
             childbearing potential are those who have not been surgically sterilized or have not&#xD;
             been free from menses for &gt; 1 year&#xD;
&#xD;
          -  Male subjects should agree to use an adequate method of contraception starting with&#xD;
             the first dose of study therapy through 200 days after the last dose of study therapy&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Has received prior therapy with IL-2 or other investigational systemic cytokine&#xD;
             therapy signaling through a common gamma-chain cytokine receptor including IL-7, IL-15&#xD;
             or IL-21&#xD;
&#xD;
          -  Is currently participating in or has participated in a study of an investigational&#xD;
             agent or using an investigational device within 4 weeks of the first dose of treatment&#xD;
&#xD;
          -  Has had a prior monoclonal antibody within 4 weeks prior to study day I. Has had prior&#xD;
             chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks&#xD;
             prior to study day 1&#xD;
&#xD;
          -  Adverse events due to prior treatment must be resolved to &lt; grade 1&#xD;
&#xD;
             * Note: If subject received major surgery, they must have recovered adequately from&#xD;
             the toxicity and/or complications from the intervention prior to starting therapy&#xD;
&#xD;
          -  For patients previously treated with checkpoint blocking antibodies, no history of&#xD;
             myocarditis, pneumonitis or nephritis of any grade associated with the prior treatment&#xD;
&#xD;
          -  Has had autoimmune toxicity associated with prior checkpoint blocking antibodies&#xD;
             requiring more than one drug class of immune suppressive therapy to resolve (e.g.&#xD;
             steroid-refractory toxicity requiring infliximab, mycophenolate mofetil, tacrolimus or&#xD;
             other immune suppressive agent) or requiring continuous immune suppression &gt; 12 weeks,&#xD;
             or having a severity judged to be life threatening by the investigator&#xD;
&#xD;
          -  Has a known additional malignancy that is progressing or requires active treatment;&#xD;
             exceptions include locally curable cancers such as basal cell carcinoma of the skin,&#xD;
             squamous cell carcinoma of the skin, superficial bladder cancer, or carcinoma in situ&#xD;
             of the cervix or breast that has undergone potentially curative therapy&#xD;
&#xD;
          -  Has known active central nervous system (CNS) metastases and/or carcinomatous&#xD;
             meningitis&#xD;
&#xD;
               -  (Dose level 1) subjects with previously treated brain metastases may participate&#xD;
                  provided they are stable (without evidence of progression by imaging for at least&#xD;
                  four weeks prior to the first dose of trial treatment and any neurologic symptoms&#xD;
                  have returned to baseline), have no evidence of new or enlarging brain&#xD;
                  metastases, and are not using steroids for at least 7 days prior to trial&#xD;
                  treatment&#xD;
&#xD;
               -  (Dose Level 2 and 3) subjects may not have any history of or current CNS&#xD;
                  metastases; baseline imaging of the brain is required within 28 days prior to the&#xD;
                  start of study treatments&#xD;
&#xD;
          -  Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any&#xD;
             other form of immunosuppressive therapy within 7 days prior to the first dose of trial&#xD;
             treatment&#xD;
&#xD;
          -  Has an active autoimmune disease requiring systemic treatment within the past 3 months&#xD;
             or a documented history of clinically severe autoimmune disease, or a syndrome that&#xD;
             requires systemic steroids or immunosuppressive agents; subjects with vitiligo or&#xD;
             resolved childhood asthma/atopy would be an exception to this rule; subjects that&#xD;
             require intermittent use of bronchodilators or local steroid injections would not be&#xD;
             excluded from the study; subjects with hypothyroidism stable on hormone replacement or&#xD;
             Sjorgen's syndrome will not be excluded from the study&#xD;
&#xD;
          -  Has history of (non-infectious) pneumonitis that required steroids or active,&#xD;
             non-infectious pneumonitis&#xD;
&#xD;
          -  Ongoing symptomatic cardiac dysrhythmias, uncontrolled atrial fibrillation, or&#xD;
             prolongation of the corrected QT interval defined as &gt; 450 msec for males and &gt; 470&#xD;
             msec for female&#xD;
&#xD;
          -  History of any of the following cardiovascular conditions within 6 months of&#xD;
             enrollment: cardiac angioplasty or stenting, myocardial infarction, unstable angina,&#xD;
             coronary artery bypass graft surgery, class III or IV congestive heart failure as&#xD;
             defined by the New York Heart Association, symptomatic peripheral vascular disease,&#xD;
             cerebrovascular accident, or transient ischemic attack&#xD;
&#xD;
          -  Has an active infection requiring systemic therapy&#xD;
&#xD;
          -  Has a history or current evidence of any condition, therapy, or laboratory abnormality&#xD;
             that might confound the results of the trial, interfere with the subject's&#xD;
             participation for the full duration of the trial, or is not in the best interest of&#xD;
             the subject to participate, in the opinion of the treating investigator&#xD;
&#xD;
          -  Has known psychiatric or substance abuse disorders that would interfere with&#xD;
             cooperation with the requirements of the trial&#xD;
&#xD;
          -  Is pregnant or breastfeeding, or expecting to conceive or father children within the&#xD;
             projected duration of the trial, starting with the pre-screening or screening visit&#xD;
             through 120 days after the last dose of trial treatment&#xD;
&#xD;
          -  Has a known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies)&#xD;
&#xD;
          -  Has known active hepatitis B (e.g., hepatitis B surface antigen [HBsAg] reactive) or&#xD;
             hepatitis C (e.g., hepatitis C virus [HCV] ribonucleic acid [RNA] [qualitative] is&#xD;
             detected)&#xD;
&#xD;
          -  Has received a live vaccine within 30 days prior to the first dose of trial treatment;&#xD;
             administration of killed vaccines are allowed; Note: Seasonal influenza vaccines for&#xD;
             injection are generally inactivated flu vaccines and are allowed&#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>Scott S. Tykodi</last_name>
    <role>Principal Investigator</role>
    <affiliation>Fred Hutch/University of Washington Cancer Consortium</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Fred Hutch/University of Washington Cancer Consortium</name>
      <address>
        <city>Seattle</city>
        <state>Washington</state>
        <zip>98109</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2023</verification_date>
  <study_first_submitted>August 21, 2017</study_first_submitted>
  <study_first_submitted_qc>August 21, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 24, 2017</study_first_posted>
  <last_update_submitted>August 16, 2023</last_update_submitted>
  <last_update_submitted_qc>August 16, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 21, 2023</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>Carcinoma</mesh_term>
    <mesh_term>Carcinoma, Renal Cell</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Aldesleukin</mesh_term>
    <mesh_term>Pembrolizumab</mesh_term>
    <mesh_term>Interleukin-2</mesh_term>
    <mesh_term>Immunoglobulins</mesh_term>
    <mesh_term>Immunoglobulin G</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/NCT03260504
org study id: 9611
secondary id: NCI-2017-01416
secondary id: RG1717068
nct id: NCT03260504
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This phase I trial studies the side effects and best dose of aldesleukin when given together
      with pembrolizumab in treating patients with kidney cancer that has spread to other parts of
      the body. Aldesleukin may stimulate white blood cells to kill kidney cancer cells.
      Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune
      system attack the cancer, and may interfere with the ability of tumor cells to avoid
      recognition by immune cells. Giving aldesleukin and pembrolizumab may work better in treating
      patients with kidney cancer.
OUTLINE: This is a dose-escalation study of aldesleukin.

      Patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1. Patients also
      receive aldesleukin subcutaneously (SC) 5 days per week for 6 weeks; or aldesleukin IV on
      days 2-6 of pembrolizumab cycles 1 and 2. Pembrolizumab treatment repeats every 3 weeks for 4
      cycles per treatment course in the absence of clinical disease progression or unacceptable
      toxicity.

      After completion of study treatment, patients are followed up via surveillance scans for
      every 3 months for up to 1 year or until disease progression.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Incidence of adverse events
time frame: Duration of study participation and Surveillance Follow up.
description: Assessed by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version (v) 5.0.
measure: Anti-tumor activity
time frame: At baseline and every 3 months
description: Tumor imaging post-treatment compared to baseline imaging; assessed by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
measure: Overall response rate (ORR)
time frame: At baseline and every 3 months
description: Assessed by RECIST 1.1
measure: Disease control rate (DCR)
time frame: At baseline and every 3 months
description: Assessed by RECIST 1.1.
measure: Progression free survival (PFS)
time frame: At baseline and every 3 months
description: PFS will be evaluated using the method of Kaplan-Meier. Median PFS times and associated 95% confidence interval will also be calculated
measure: Change in performance status
time frame: Duration of study participation and Surveillance Follow up.
description: Assessed by Eastern Cooperative Oncology Group (ECOG) Performance Scale
measure: PD-L1 expression
time frame: Retrospective after completion of enrollment
description: Will be assessed by immunohistochemistry.
measure: Absolute numbers of regulatory T cells (Treg)
time frame: Retrospective after completion of enrollment
description: Will assess the ratio of Treg and effector T cells. Analyses of T cell subsets will be correlated with clinical outcomes.
measure: Absolute numbers of effector T cells (Teff)
time frame: Retrospective after completion of enrollment
description: Will assess the ratio of Treg and Teff. Analyses of T cell subsets will be correlated with clinical outcomes.
measure: De novo 5T4 specific humoral and/or cellular immune responses
time frame: Retrospective after completion of enrollment
description: Will be analyzed as a potential marker of "on target" effective anti-tumor immunity and correlated with clinical response.
measure: Tumor infiltrating lymphocytes (TIL) clonality score
time frame: Retrospective after completion of enrollment
description: TIL clonality score will be correlated with clinical outcomes of renal cell carcinoma (RCC) patients treated with IL-2 plus pembrolizumab.
measure: Chromosomal copy number alterations
time frame: Retrospective after completion of enrollment
description: OncoScan chromosomal array analyses will be carried out on archived tumor for RCC patients treated with IL-2 and pembrolizumab and chromosomal numerical abnormalities (CNAs) correlated to objective response rate.
arm group label: Treatment (pembrolizumab, aldesleukin)
arm group type: Experimental
description: Patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1. Patients also receive aldesleukin subcutaneously (SC) 5 days per week for 6 weeks; or aldesleukin IV on days 2-6 of pembrolizumab cycles 1 and 2. Pembrolizumab treatment repeats every 3 weeks for 4 cycles per treatment course in the absence of clinical disease progression or unacceptable toxicity.
intervention type: Biological
intervention name: Aldesleukin
description: Given SC or IV
arm group label: Treatment (pembrolizumab, aldesleukin)
other name: 125-L-Serine-2-133-interleukin 2
other name: Proleukin
other name: r-serHuIL-2
other name: Recombinant Human IL-2
other name: Recombinant Human Interleukin-2
intervention type: Biological
intervention name: Pembrolizumab
description: Given IV
arm group label: Treatment (pembrolizumab, aldesleukin)
other name: Keytruda
other name: Lambrolizumab
other name: MK-3475
other name: SCH 900475
other name: Immunoglobulin G4
other name: Anti-(Human Programmed Cell Death 1)
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Scott S. Tykodi
role: Principal Investigator
affiliation: Fred Hutch/University of Washington Cancer Consortium
facility: 
country: United States
responsible party type: Sponsor
mesh term: Carcinoma
mesh term: Carcinoma, Renal Cell
mesh term: Aldesleukin
mesh term: Pembrolizumab
mesh term: Interleukin-2
mesh term: Immunoglobulins
mesh term: Immunoglobulin G
sharing ipd: No