<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/NCT01672775</url>
  </required_header>
  <id_info>
    <org_study_id>AGS-16C3F-12-2</org_study_id>
    <nct_id>NCT01672775</nct_id>
  </id_info>
  <brief_title>A Study to Assess the Safety, Pharmacokinetics and Effectiveness of AGS-16C3F Monotherapy in Subjects With Renal Cell Carcinoma (RCC) of Clear Cell or Papillary Histology</brief_title>
  <official_title>A Phase 1, Open Label, Multi-center Study to Assess the Safety, Pharmacokinetics and Effectiveness of AGS-16C3F Monotherapy in Subjects With Renal Cell Carcinoma (RCC) of Clear Cell or Papillary Histology</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Agensys, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Astellas Pharma Inc</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to evaluate the safety and pharmacokinetics and assess the&#xD;
      immunogenicity and effectiveness of AGS-16C3F in subjects with renal cell cancer (RCC).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The study has two components. The first aims to establish a safe dose for AGS-16C3F. Once&#xD;
      identified, the safety and effectiveness will be tested in additional subjects with either&#xD;
      clear cell or papillary histology in expanded cohorts.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 18, 2012</start_date>
  <completion_date type="Actual">February 21, 2017</completion_date>
  <primary_completion_date type="Actual">February 21, 2017</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>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>24 months</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetic profile for total antibody (TAb), antibody drug conjugate (ADC), and monomethyl auristatin F (MMAF): Ceoi or Cmax, Ctrough, Tmax, AUCτ, t1/2, CL, and Vss</measure>
    <time_frame>Days 1, 2, 3, 4, 8, 15, 22, 43, 64, 65, 66, 67, 71, 78, and 92</time_frame>
    <description>Concentration at end of infusion (Ceoi) or maximum observed concentrations (Cmax), Trough concentration (Ctrough), time to maximum concentration (Tmax), partial area under the serum concentration-time curve (AUCτ), terminal or apparent half-life (t1/2), systemic clearance (CL), and volume of distribution at steady state (Vss)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of antidrug antibody formation to human native antibody (AGS-16C) and antibody drug conjugate (AGS-16C3F)</measure>
    <time_frame>24 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Tumor response: objective response rate</measure>
    <time_frame>24 months</time_frame>
    <description>Determined from the subjects' best response and will include complete response (CR) and partial response (PR)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Tumor response: disease control rate</measure>
    <time_frame>24 months</time_frame>
    <description>Determined from the subjects' best response will include complete response (CR) partial response (PR), and stable disease (SD)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Tumor response: Changes in bone scans</measure>
    <time_frame>Baseline, Week 13 and every 12 weeks thereafter</time_frame>
  </secondary_outcome>
  <number_of_arms>8</number_of_arms>
  <enrollment type="Actual">34</enrollment>
  <condition>Carcinoma, Renal Cell</condition>
  <condition>Renal Cell Carcinoma of Papillary Histology</condition>
  <condition>Renal Cell Carcinoma With Clear Cell Histology</condition>
  <condition>Renal Cell Carcinoma With Non-Clear Cell Histology</condition>
  <arm_group>
    <arm_group_label>Cohort 1 AGS-16C3F highest dose</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Renal Cell Carcinoma subjects with clear and non-clear histology</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 0 AGS-16C3F higher dose</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Renal Cell Carcinoma subjects with clear and non-clear histology</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort (-1) AGS-16C3F high dose</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Renal Cell Carcinoma subjects with clear and non-clear histology</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort (-2) AGS-16C3F middle dose</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Renal Cell Carcinoma subjects with clear and non-clear histology</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort (-3) AGS-16C3F low dose</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Renal Cell Carcinoma subjects with clear and non-clear histology</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort (-4) AGS-16C3F lowest dose</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Renal Cell Carcinoma subjects with clear and non-clear histology</description>
  </arm_group>
  <arm_group>
    <arm_group_label>AGS-16C3F in RCC Subjects with Clear Cell Histology</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Expansion Cohort</description>
  </arm_group>
  <arm_group>
    <arm_group_label>AGS-16C3F in RCC Subjects with Papillary Histology</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Expansion Cohort</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>AGS-16C3F</intervention_name>
    <description>intravenous (IV) infusion</description>
    <arm_group_label>AGS-16C3F in RCC Subjects with Clear Cell Histology</arm_group_label>
    <arm_group_label>AGS-16C3F in RCC Subjects with Papillary Histology</arm_group_label>
    <arm_group_label>Cohort (-1) AGS-16C3F high dose</arm_group_label>
    <arm_group_label>Cohort (-2) AGS-16C3F middle dose</arm_group_label>
    <arm_group_label>Cohort (-3) AGS-16C3F low dose</arm_group_label>
    <arm_group_label>Cohort (-4) AGS-16C3F lowest dose</arm_group_label>
    <arm_group_label>Cohort 0 AGS-16C3F higher dose</arm_group_label>
    <arm_group_label>Cohort 1 AGS-16C3F highest dose</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Dose determination cohorts: Histologically confirmed diagnosis of metastatic RCC of&#xD;
             either clear cell or non-clear histology.&#xD;
&#xD;
               -  Tumors with clear cell histology: subject must have progressed after at least one&#xD;
                  anti-vascular endothelial growth factor receptor (anti-VEGFR) therapy&#xD;
&#xD;
               -  Tumors with non-clear cell histology must be ectonucleotide&#xD;
                  pyrophosphatase/phosphodiesterase family member 3 (ENPP3) positive at&#xD;
                  pre-screening. This sub-group does not have any prior therapy requirement.&#xD;
&#xD;
          -  Dose expansion cohorts: Histologically confirmed diagnosis of metastatic RCC of either&#xD;
             clear cell or papillary histology&#xD;
&#xD;
               -  Tumors with clear cell histology: subject must have progressed after at least one&#xD;
                  anti-VEGFR therapy&#xD;
&#xD;
               -  Tumors with papillary histology: includes unclassified histology with papillary&#xD;
                  features and must be ENPP3 positive at pre-screening. This sub-group does not&#xD;
                  have any prior therapy requirement.&#xD;
&#xD;
          -  Measurable disease according to Response Criteria for Solid Tumors (RECIST Version&#xD;
             1.1)&#xD;
&#xD;
          -  Eastern Cooperative Group (ECOG) performance status of 0-1&#xD;
&#xD;
          -  Hematologic function, as follows:&#xD;
&#xD;
               -  Absolute neutrophil count (ANC) ≥ 1.5 x 109/L&#xD;
&#xD;
               -  Platelet count ≥ 100 x 109/L&#xD;
&#xD;
               -  Hemoglobin ≥ 9 g/dL (transfusions are allowed)&#xD;
&#xD;
          -  Renal function, as follows:&#xD;
&#xD;
               -  creatinine ≤ 1.5 x upper limit of normal (ULN), or calculated glomerular&#xD;
                  filtration rate (GFR) &gt; 50 mL/min if creatinine &gt; 1.5x ULN&#xD;
&#xD;
          -  Hepatic function, as follows:&#xD;
&#xD;
               -  Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) ≤ 2.5 x ULN&#xD;
                  or ≤ 5x ULN if known liver metastases&#xD;
&#xD;
               -  Total bilirubin ≤1.5 x ULN&#xD;
&#xD;
          -  International normalized ratio (INR) &lt; 1.3 (or ≤ 3.0 if on therapeutic&#xD;
             anticoagulation)&#xD;
&#xD;
          -  Women and men of childbearing potential must be advised and agree to practice&#xD;
             effective methods of contraception during the course of the study and for 4 weeks&#xD;
             after the last AGS-16C3F infusion administration&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Current uncontrolled central nervous system (CNS) metastasis or malignant brain tumors&#xD;
&#xD;
          -  Use of any investigational drug (including marketed drugs not approved for this&#xD;
             indication) within 4 weeks prior to screening. No time limit applies to the use of&#xD;
             marketed drugs approved for this indication provided that the subject has progressed&#xD;
             on the treatment and all toxicities attributable to the drug have resolved or returned&#xD;
             to baseline&#xD;
&#xD;
          -  Known sensitivity to any of the ingredients of the investigational product AGS-16C3F&#xD;
&#xD;
          -  History of thromboembolic events and bleeding disorders ≤3 months (e.g., (deep vein&#xD;
             thrombosis) DVT or pulmonary embolism (PE))&#xD;
&#xD;
          -  Active angina or Class III or IV Congestive Heart Failure (CHF) (New York Heart&#xD;
             Association CHF Functional Classification System) or clinically significant cardiac&#xD;
             disease within 12 months of study enrollment, including myocardial infarction,&#xD;
             unstable angina, grade 2 or greater peripheral vascular disease, congestive heart&#xD;
             failure, uncontrolled hypertension, or arrhythmias not controlled by outpatient&#xD;
             medication.&#xD;
&#xD;
          -  Major surgery within 4 weeks of study enrollment&#xD;
&#xD;
          -  Women who are pregnant (confirmed by positive pregnancy test) or lactating&#xD;
&#xD;
          -  Known positive test for human immunodeficiency virus (HIV), hepatitis C, or hepatitis&#xD;
             B surface antigen.&#xD;
&#xD;
          -  Active infection requiring treatment with systemic (intravenous or oral)&#xD;
             anti-infectives (antibiotic, antifungal, or antiviral agent) within 72 hours of&#xD;
             screening.&#xD;
&#xD;
          -  History of eye surgery within 6 months, presence of cataracts or other ocular&#xD;
             disorders significantly affecting vision&#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>Medical Director</last_name>
    <role>Study Director</role>
    <affiliation>Agensys, Inc.</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Site US00005 University of Michigan Medical Center</name>
      <address>
        <city>Ann Arbor</city>
        <state>Michigan</state>
        <zip>48109</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Site US00003 Karmanos Cancer Institute</name>
      <address>
        <city>Detroit</city>
        <state>Michigan</state>
        <zip>48201</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Site US00004 Roswell Park Cancer Institute</name>
      <address>
        <city>Buffalo</city>
        <state>New York</state>
        <zip>14263</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Site US00002 Memorial Sloan-Kettering Cancer Center</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10065</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Site US00001 Seattle Cancer Care Alliance</name>
      <address>
        <city>Seattle</city>
        <state>Washington</state>
        <zip>98109</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Site CA00006 Cross Cancer Institute</name>
      <address>
        <city>Edmonton</city>
        <state>Alberta</state>
        <zip>T6G 1Z2</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Site CA00008 British Columbia Cancer Agency</name>
      <address>
        <city>Vancouver</city>
        <state>British Columbia</state>
        <zip>V5Z 4E6</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Site CA00009 London Health Sciences Centre</name>
      <address>
        <city>London</city>
        <state>Ontario</state>
        <zip>N6A 4L6</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Site CA00007 Jewish General Hospital</name>
      <address>
        <city>Montreal</city>
        <state>Quebec</state>
        <zip>H3T 1E2</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
    <country>United States</country>
  </location_countries>
  <link>
    <url>https://astellasclinicalstudyresults.com/patientStudySearch.aspx?RID=;;;AGS-16C3F-12-2</url>
    <description>Link to results on the Astellas Clinical Study Results website.</description>
  </link>
  <verification_date>December 2020</verification_date>
  <study_first_submitted>August 22, 2012</study_first_submitted>
  <study_first_submitted_qc>August 22, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 27, 2012</study_first_posted>
  <last_update_submitted>December 16, 2020</last_update_submitted>
  <last_update_submitted_qc>December 16, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">December 19, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Renal Cell Carcinoma</keyword>
  <keyword>AGS-16C3F</keyword>
  <keyword>Pharmacokinetics of AGS-16C3F</keyword>
  <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>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>Access to anonymized individual participant level data will not be provided for this trial as it meets one or more of the exceptions described on www.clinicalstudydatarequest.com under &quot;Sponsor Specific Details for Astellas.&quot;</ipd_description>
  </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/NCT01672775
org study id: AGS-16C3F-12-2
nct id: NCT01672775
lead sponsor: 
has dmc: No
The purpose of this study is to evaluate the safety and pharmacokinetics and assess the
      immunogenicity and effectiveness of AGS-16C3F in subjects with renal cell cancer (RCC).
The study has two components. The first aims to establish a safe dose for AGS-16C3F. Once
      identified, the safety and effectiveness will be tested in additional subjects with either
      clear cell or papillary histology in expanded cohorts.
allocation: Non-Randomized
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Incidence of Adverse Events
time frame: 24 months
measure: Pharmacokinetic profile for total antibody (TAb), antibody drug conjugate (ADC), and monomethyl auristatin F (MMAF): Ceoi or Cmax, Ctrough, Tmax, AUCτ, t1/2, CL, and Vss
time frame: Days 1, 2, 3, 4, 8, 15, 22, 43, 64, 65, 66, 67, 71, 78, and 92
description: Concentration at end of infusion (Ceoi) or maximum observed concentrations (Cmax), Trough concentration (Ctrough), time to maximum concentration (Tmax), partial area under the serum concentration-time curve (AUCτ), terminal or apparent half-life (t1/2), systemic clearance (CL), and volume of distribution at steady state (Vss)
measure: Incidence of antidrug antibody formation to human native antibody (AGS-16C) and antibody drug conjugate (AGS-16C3F)
time frame: 24 months
measure: Tumor response: objective response rate
time frame: 24 months
description: Determined from the subjects' best response and will include complete response (CR) and partial response (PR)
measure: Tumor response: disease control rate
time frame: 24 months
description: Determined from the subjects' best response will include complete response (CR) partial response (PR), and stable disease (SD)
measure: Tumor response: Changes in bone scans
time frame: Baseline, Week 13 and every 12 weeks thereafter
arm group label: Cohort 1 AGS-16C3F highest dose
arm group type: Experimental
description: Renal Cell Carcinoma subjects with clear and non-clear histology
arm group label: Cohort 0 AGS-16C3F higher dose
arm group type: Experimental
description: Renal Cell Carcinoma subjects with clear and non-clear histology
arm group label: Cohort (-1) AGS-16C3F high dose
arm group type: Experimental
description: Renal Cell Carcinoma subjects with clear and non-clear histology
arm group label: Cohort (-2) AGS-16C3F middle dose
arm group type: Experimental
description: Renal Cell Carcinoma subjects with clear and non-clear histology
arm group label: Cohort (-3) AGS-16C3F low dose
arm group type: Experimental
description: Renal Cell Carcinoma subjects with clear and non-clear histology
arm group label: Cohort (-4) AGS-16C3F lowest dose
arm group type: Experimental
description: Renal Cell Carcinoma subjects with clear and non-clear histology
arm group label: AGS-16C3F in RCC Subjects with Clear Cell Histology
arm group type: Experimental
description: Expansion Cohort
arm group label: AGS-16C3F in RCC Subjects with Papillary Histology
arm group type: Experimental
description: Expansion Cohort
intervention type: Drug
intervention name: AGS-16C3F
description: intravenous (IV) infusion
arm group label: AGS-16C3F in RCC Subjects with Clear Cell Histology
arm group label: AGS-16C3F in RCC Subjects with Papillary Histology
arm group label: Cohort (-1) AGS-16C3F high dose
arm group label: Cohort (-2) AGS-16C3F middle dose
arm group label: Cohort (-3) AGS-16C3F low dose
arm group label: Cohort (-4) AGS-16C3F lowest dose
arm group label: Cohort 0 AGS-16C3F higher dose
arm group label: Cohort 1 AGS-16C3F highest dose
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Medical Director
role: Study Director
affiliation: Agensys, Inc.
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Canada
country: United States
url: https://astellasclinicalstudyresults.com/patientStudySearch.aspx?RID=;;;AGS-16C3F-12-2
description: Link to results on the Astellas Clinical Study Results website.
responsible party type: Sponsor
mesh term: Carcinoma
mesh term: Carcinoma, Renal Cell
sharing ipd: No
ipd description: Access to anonymized individual participant level data will not be provided for this trial as it meets one or more of the exceptions described on www.clinicalstudydatarequest.com under "Sponsor Specific Details for Astellas."