<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/NCT03792841</url>
  </required_header>
  <id_info>
    <org_study_id>20180101</org_study_id>
    <nct_id>NCT03792841</nct_id>
  </id_info>
  <brief_title>Safety, Tolerability, Pharmacokinetics, and Efficacy of Acapatamab in Subjects With mCRPC</brief_title>
  <official_title>A Phase 1 Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Efficacy of Prostate Specific Membrane Antigen Half-life Extended Bispecific T-cell Engager Acapatamab in Subjects With Metastatic Castration-resistant Prostate Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Amgen</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Amgen</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>
      A phase 1 study evaluating the safety, tolerability, pharmacokinetics, and efficacy of&#xD;
      prostate specific membrane antigen half-life extended bispecific T-cell engager acapatamab in&#xD;
      subjects with metastatic castration-resistant prostate cancer, and to determine the maximum&#xD;
      tolerated dose (MTD) or recommended phase 2 dose (RP2D).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a phase I, first-in-human study to evaluate the safety and tolerability of&#xD;
      acapatamab; a half-life extended (HLE) bispecific T-cell engager (BiTE®) construct, alone and&#xD;
      in combination with pembrolizumab, etanercept prophylaxis and cytochrome P450 (CYP)&#xD;
      phenotyping cocktail in subjects with metastatic castration-resistant prostate cancer.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">February 5, 2019</start_date>
  <completion_date type="Actual">July 3, 2023</completion_date>
  <primary_completion_date type="Actual">July 3, 2023</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>Sequential Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of participants with dose-limiting toxicity</measure>
    <time_frame>Up to 3 years</time_frame>
    <description>Parts 1, 2, 3, 4, 5, and 6 of the study</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of participants with treatment-emergent adverse events</measure>
    <time_frame>Up to 3 years</time_frame>
    <description>Parts 1, 2, 3, 4, 5, and 6 of the study</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of participants with treatment-related adverse events</measure>
    <time_frame>Up to 3 years</time_frame>
    <description>Parts 1, 2, 3, 4, 5, and 6 of the study</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of participants with clinically significant changes in vital signs</measure>
    <time_frame>Up to 3 years</time_frame>
    <description>Parts 1, 2, 3, 4, 5, and 6 of the study</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of participants with clinically significant changes in electrocardiogram (ECG)</measure>
    <time_frame>Up to 3 years</time_frame>
    <description>Parts 1, 2, 3, 4, 5, and 6 of the study</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of participants with clinically significant changes in clinical laboratory tests</measure>
    <time_frame>Up to 3 years</time_frame>
    <description>Parts 1, 2, 3, 4, 5, and 6 of the study</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Maximum serum concentration (Cmax) of acapatamab</measure>
    <time_frame>Up to 3 years</time_frame>
    <description>Parts 1, 2, 3, 4, 5, and 6 of the study</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Minimum serum concentration (Cmin) of acapatamab</measure>
    <time_frame>Up to 3 years</time_frame>
    <description>Parts 1, 2, 3, 4, 5, and 6 of the study</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area under the concentration-time curve (AUC) over the dosing interval of acapatamab</measure>
    <time_frame>Up to 3 years</time_frame>
    <description>Parts 1, 2, 3, 4, 5, and 6 of the study</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Accumulation ratio of acapatamab</measure>
    <time_frame>Up to 3 years</time_frame>
    <description>Parts 1, 2, 3, 4, 5, and 6 of the study</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Half-life of acapatamab</measure>
    <time_frame>Up to 3 years</time_frame>
    <description>Parts 1, 2, 3, 4, 5, and 6 of the study</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Objective response (OR)</measure>
    <time_frame>Up to 3 years</time_frame>
    <description>Parts 1, 2, 3, 4, 5, and 6 of the study</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Prostate-specific antigen (PSA) response</measure>
    <time_frame>Up to 3 years</time_frame>
    <description>Parts 1, 2, 3, 4, 5, and 6 of the study</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of response (DOR) (radiographic and PSA)</measure>
    <time_frame>Up to 3 years</time_frame>
    <description>Parts 1, 2, 3, 4, 5, and 6 of the study</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of participants experiencing a response based on 68Gallium (68Ga)-prostate-specific membrane antigen (PSMA)-11 positron emission tomography (PET)/computed tomography (CT) response evaluations</measure>
    <time_frame>Up to 3 years</time_frame>
    <description>Parts 1, 2 and 3 only.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of participants experiencing a response based on 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) response evaluations</measure>
    <time_frame>Up to 3 years</time_frame>
    <description>Parts 1, 2 and 3 only.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in time to progression (radiographic and PSA)</measure>
    <time_frame>Up to 3 years</time_frame>
    <description>Parts 1, 2, 3, 4, 5, and 6 of the study</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression-free survival (PFS) (radiographic and PSA)</measure>
    <time_frame>Up to 3 years</time_frame>
    <description>Parts 1, 2, 3, 4, 5, and 6 of the study.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>1, 2 and 3-year overall survival (OS)</measure>
    <time_frame>Up to 3 years</time_frame>
    <description>Parts 1, 2, 3, 4, 5, and 6 of the study</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of participants experiencing circulating tumor cells (CTC) response</measure>
    <time_frame>Up to 3 years</time_frame>
    <description>Parts 1, 2, 3, 4, 5, and 6 of the study. CTC response defined as CTC0 (reduction of CTCs &gt; 0 to 0) or CTC conversion (≥ 5 CTCs/7.5 mL blood to ≤ 4 CTCs/7.5 mL blood)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Other PCWG3-recommended endpoints - time to symptomatic skeletal events</measure>
    <time_frame>Up to 3 years</time_frame>
    <description>Parts 1, 2, 3, 4, 5, and 6 of the study</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Other PCWG3-recommended endpoints - lactate dehydrogenase [LDH] levels</measure>
    <time_frame>Up to 3 years</time_frame>
    <description>Parts 1, 2, 3, 4, 5, and 6 of the study</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Other PCWG3-recommended endpoints - hemoglobin levels</measure>
    <time_frame>Up to 3 years</time_frame>
    <description>Parts 1, 2, 3, 4, 5, and 6 of the study</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Other PCWG3-recommended endpoints - neutrophil-to-lymphocyte ratio</measure>
    <time_frame>Up to 3 years</time_frame>
    <description>Parts 1, 2, 3, 4, 5, and 6 of the study</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Other PCWG3-recommended endpoints - urine N-telopeptide levels</measure>
    <time_frame>Up to 3 years</time_frame>
    <description>Parts 1, 2, 3, 4, 5, and 6 of the study</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Other PCWG3-recommended endpoints - alkaline phosphatase [total, bone] levels</measure>
    <time_frame>Up to 3 years</time_frame>
    <description>Parts 1, 2, 3, 4, 5, and 6 of the study</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximum serum concentration (Cmax) of acapatamab when administered with CYP enzymes</measure>
    <time_frame>Up to 3 years</time_frame>
    <description>Part 6 only.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area under the concentration-time curve over a 24-hour period (AUC24) of acapatamab when administered with CYP enzymes</measure>
    <time_frame>Up to 3 years</time_frame>
    <description>Part 6 only.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Half-life of acapatamab when administered with CYP enzymes</measure>
    <time_frame>Up to 3 years</time_frame>
    <description>Part 6 only.</description>
  </secondary_outcome>
  <number_of_arms>7</number_of_arms>
  <enrollment type="Actual">212</enrollment>
  <condition>Metastatic Castration-resistant Prostate Cancer</condition>
  <condition>Prostate Cancer</condition>
  <arm_group>
    <arm_group_label>Part 1 Dose-exploration: acapatamab treatment</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Part 1 dose-exploration: acapatamab is administered intravenously. The dose-exploration phase of the study will estimate the MTD of acapatamab. RP2D may be identified based on emerging safety, efficacy, and pharmacodynamic data prior to reaching an MTD.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 1 Dose-expansion: acapatamab treatment</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Part 1 dose-expansion: acapatamab is administered intravenously at the MTD/RP2D.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 2: acapatamab + Pembrolizumab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Part 2: acapatamab is administered intravenously at the MTD/RP2D. Pembrolizumab will be administered intravenously.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 3: acapatamab + Etanercept Prophylaxis</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Part 3: acapatamab is administered intravenously at RP2D/MTD levels. Etanercept will be administered subcutaneously in cycle 1 only.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 4: acapatamab 24 Hour Monitoring</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Part 4: acapatamab is administered intravenously at RP2D/MTD with 24-hour monitoring.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 5: acapatamab Outpatient Cohort</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Part 5: acapatamab is administered intravenously at RP2D/MTD in an outpatient setting with 8-hour monitoring.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 6: acapatamab + Cytochrome P450 (CYP) Cocktail Drug Interaction</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Part 6: acapatamab is administered intravenously at RP2D/MTD. A CYP phenotyping cocktail will be administered orally.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>acapatamab</intervention_name>
    <description>Investigational immunotherapy for the treatment of metastatic castration-resistant prostate cancer</description>
    <arm_group_label>Part 1 Dose-expansion: acapatamab treatment</arm_group_label>
    <arm_group_label>Part 1 Dose-exploration: acapatamab treatment</arm_group_label>
    <arm_group_label>Part 2: acapatamab + Pembrolizumab</arm_group_label>
    <arm_group_label>Part 3: acapatamab + Etanercept Prophylaxis</arm_group_label>
    <arm_group_label>Part 4: acapatamab 24 Hour Monitoring</arm_group_label>
    <arm_group_label>Part 5: acapatamab Outpatient Cohort</arm_group_label>
    <arm_group_label>Part 6: acapatamab + Cytochrome P450 (CYP) Cocktail Drug Interaction</arm_group_label>
    <other_name>PSMA Targeted Therapy</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Pembrolizumab</intervention_name>
    <description>Combined with acapatamab for investigational treatment of mCRPC</description>
    <arm_group_label>Part 2: acapatamab + Pembrolizumab</arm_group_label>
    <other_name>PD-1 inhibitor</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Etanercept</intervention_name>
    <description>Prophylaxis for acapatamab-related cytokine release syndrome.</description>
    <arm_group_label>Part 3: acapatamab + Etanercept Prophylaxis</arm_group_label>
    <other_name>TNF-alpha inhibitor</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cytochrome P450 (CYP) Cocktail</intervention_name>
    <description>Evaluate the effect of co-administration of multiple dosing of acapatamab on plasma</description>
    <arm_group_label>Part 6: acapatamab + Cytochrome P450 (CYP) Cocktail Drug Interaction</arm_group_label>
    <other_name>Cooperstown 5+1 CYP phenotyping cocktail</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        All Parts&#xD;
&#xD;
        Inclusion Criteria:&#xD;
&#xD;
          -  Subject has provided informed consent prior to initiation of any study specific&#xD;
             activities/procedures&#xD;
&#xD;
          -  Subjects with histologically or cytologically confirmed mCRPC who are refractory to a&#xD;
             novel antiandrogen therapy (abiraterone, enzalutamide, and/or apalutamide) and have&#xD;
             failed at least 1 (but not more than 2) taxane regimens (or who are deemed medically&#xD;
             unsuitable to be treated with a taxane regimen or have actively refused treatment with&#xD;
             a taxane regimen). Progression on novel antiandrogen therapy may have occurred in the&#xD;
             non-metastatic CRPC setting&#xD;
&#xD;
          -  Subjects must have undergone bilateral orchiectomy or must be on continuous ADT with a&#xD;
             gonadotropin releasing hormone (GnRH) agonist or antagonist&#xD;
&#xD;
          -  Total serum testosterone &lt;/= 50 ng/dL or 1.7 nmol/L&#xD;
&#xD;
          -  Evidence of progressive disease, defined as 1 or more PCWG3 criteria:&#xD;
&#xD;
          -  PSA level &gt;/= 1 ng/mL that has increased on at least 2 successive occasions at least 1&#xD;
             week apart&#xD;
&#xD;
          -  nodal or visceral progression as defined by RECIST 1.1 with PCGW3 modifications&#xD;
&#xD;
          -  appearance of 2 or more new lesions in bone scan&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 1&#xD;
&#xD;
          -  Life expectancy &gt;/= 6months&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Any anticancer therapy or immunotherapy within 4 weeks of start of first dose, not&#xD;
             including luteinizing hormone-releasing hormone agonist (LHRH)/GnRH analogue&#xD;
             (agonist/antagonist). Subjects on a stable bisophosphonate or denosumab regimen for&#xD;
             &gt;/= 30 days prior to randomization are eligible&#xD;
&#xD;
          -  Prior PSMA-targeted therapy (subjects on prior therapy may be eligible if discussed&#xD;
             with Amgen medical monitor prior to enrollment)&#xD;
&#xD;
          -  Central nervous system (CNS) metastases, leptomeningeal disease, or spinal cord&#xD;
             compression&#xD;
&#xD;
          -  Active autoimmune disease or any other diseases requiring immunosuppressive therapy&#xD;
             while on study&#xD;
&#xD;
          -  Needing chronic systemic corticosteroid therapy (prednisone &gt; 10 mg per day or&#xD;
             equivalent) or any other immunosuppressive therapies (including anti-tumor necrosis&#xD;
             factor alpha [TNF alpha] therapies) unless stopped 7 days prior to start of first dose&#xD;
&#xD;
          -  Myocardial infarction, unstable angina, cardiac arrhythmia requiring medication,&#xD;
             and/or symptomatic congestive heart failure (New York Heart Association &gt; class II)&#xD;
             within 12 months of first dose of acapatamab&#xD;
&#xD;
        Part 2 only:&#xD;
&#xD;
          -  Subjects on a prior PD-1 or PD-L1 inhibitor who experienced a Grade 3 or higher&#xD;
             immune-related adverse event prior to first day of dosing&#xD;
&#xD;
          -  History or evidence of interstitial lung disease or active, non-infectious pneumonitis&#xD;
&#xD;
        Part 3 only:&#xD;
&#xD;
        - Evidence of active tuberculosis on chest radiograph within 3 months prior to the first&#xD;
        dose of investigational product&#xD;
&#xD;
        Part 6 only:&#xD;
&#xD;
        Subjects are excluded from this cohort if any of the following additional criteria apply:&#xD;
&#xD;
          -  Subjects taking strong OAT3 inhibitors (eg, probenecid) or adjust the dosing to 1 mg&#xD;
             PO QD.&#xD;
&#xD;
          -  Subjects with latent or active tuberculosis at screening&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>MD</last_name>
    <role>Study Director</role>
    <affiliation>Amgen</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>El Camino Hospital</name>
      <address>
        <city>Campbell</city>
        <state>California</state>
        <zip>95008</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>City of Hope National Medical Center</name>
      <address>
        <city>Duarte</city>
        <state>California</state>
        <zip>91010</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>City of Hope at Long Beach Elm</name>
      <address>
        <city>Long Beach</city>
        <state>California</state>
        <zip>90813</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of California Los Angeles</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90095</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Emory University</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30322</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Indiana University</name>
      <address>
        <city>Indianapolis</city>
        <state>Indiana</state>
        <zip>46202</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Iowa Hospitals and Clinics</name>
      <address>
        <city>Iowa City</city>
        <state>Iowa</state>
        <zip>52242</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Tulane Medical Center</name>
      <address>
        <city>New Orleans</city>
        <state>Louisiana</state>
        <zip>70112</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Washington University</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63110</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Comprehensive Cancer Centers of Nevada</name>
      <address>
        <city>Las Vegas</city>
        <state>Nevada</state>
        <zip>89169</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>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>Weill Cornell Medical College</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10065</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Texas Southwestern Medical Center</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75390</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Chris OBrien Lifehouse</name>
      <address>
        <city>Camperdown</city>
        <state>New South Wales</state>
        <zip>2050</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Scientia Clinical Research Ltd</name>
      <address>
        <city>Randwick</city>
        <state>New South Wales</state>
        <zip>2031</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Peter MacCallum Cancer Centre</name>
      <address>
        <city>Parkville</city>
        <state>Victoria</state>
        <zip>3050</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ordensklinikum Linz Elisabethinen</name>
      <address>
        <city>Linz</city>
        <zip>4020</zip>
        <country>Austria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Landeskrankenhaus Salzburg</name>
      <address>
        <city>Salzburg</city>
        <zip>5020</zip>
        <country>Austria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Krankenhaus der Barmherzigen Brueder Wien</name>
      <address>
        <city>Wien</city>
        <zip>1020</zip>
        <country>Austria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitaetsklinikum Allgemeines Krankenhaus Wien</name>
      <address>
        <city>Wien</city>
        <zip>1090</zip>
        <country>Austria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universite Catholique de Louvain Cliniques Universitaires Saint Luc</name>
      <address>
        <city>Bruxelles</city>
        <zip>1200</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitair Ziekenhuis Gent</name>
      <address>
        <city>Gent</city>
        <zip>9000</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>BC Cancer Vancouver</name>
      <address>
        <city>Vancouver</city>
        <state>British Columbia</state>
        <zip>V5Z 4E6</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Institut Gustave Roussy</name>
      <address>
        <city>Villejuif Cedex</city>
        <zip>94805</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>National Cancer Center Hospital East</name>
      <address>
        <city>Kashiwa-shi</city>
        <state>Chiba</state>
        <zip>277-8577</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Yokohama City University Medical Center</name>
      <address>
        <city>Yokohama-shi</city>
        <state>Kanagawa</state>
        <zip>232-0024</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Erasmus Medisch Centrum</name>
      <address>
        <city>Rotterdam</city>
        <zip>3015 GD</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>National University Hospital</name>
      <address>
        <city>Singapore</city>
        <zip>119074</zip>
        <country>Singapore</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>National Cancer Centre Singapore</name>
      <address>
        <city>Singapore</city>
        <zip>169610</zip>
        <country>Singapore</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Linkou Chang Gung Memorial Hospital of Chang Gung Medical Foundation</name>
      <address>
        <city>Taoyuan</city>
        <zip>33305</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Australia</country>
    <country>Austria</country>
    <country>Belgium</country>
    <country>Canada</country>
    <country>France</country>
    <country>Japan</country>
    <country>Netherlands</country>
    <country>Singapore</country>
    <country>Taiwan</country>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://www.amgentrials.com</url>
    <description>AmgenTrials clinical trials website</description>
  </link>
  <verification_date>July 2023</verification_date>
  <study_first_submitted>January 2, 2019</study_first_submitted>
  <study_first_submitted_qc>January 2, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 3, 2019</study_first_posted>
  <last_update_submitted>July 11, 2023</last_update_submitted>
  <last_update_submitted_qc>July 11, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">July 12, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>acapatamab</keyword>
  <keyword>HLE-BiTE®</keyword>
  <keyword>mCRPC</keyword>
  <keyword>Metastatic Castration-resistant Prostate Cancer</keyword>
  <keyword>Prostate cancer</keyword>
  <keyword>PSMA</keyword>
  <keyword>BiTE®</keyword>
  <keyword>Bispecific T-Cell engager</keyword>
  <keyword>Immunotherapy</keyword>
  <keyword>Immuno-oncology</keyword>
  <keyword>Immunooncology</keyword>
  <keyword>Solid tumor</keyword>
  <keyword>PSMA Targeted Therapy</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Prostatic Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Etanercept</mesh_term>
    <mesh_term>Pembrolizumab</mesh_term>
    <mesh_term>Immune Checkpoint Inhibitors</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
    <ipd_info_type>Clinical Study Report (CSR)</ipd_info_type>
    <ipd_time_frame>Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication (or other new use) have been granted marketing authorization in both the US and Europe, or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.</ipd_time_frame>
    <ipd_access_criteria>Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors, and if not approved, may be further arbitrated by a Data Sharing Independent Review Panel. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the URL below.</ipd_access_criteria>
    <ipd_url>https://www.amgen.com/datasharing</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/NCT03792841
org study id: 20180101
nct id: NCT03792841
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
A phase 1 study evaluating the safety, tolerability, pharmacokinetics, and efficacy of
      prostate specific membrane antigen half-life extended bispecific T-cell engager acapatamab in
      subjects with metastatic castration-resistant prostate cancer, and to determine the maximum
      tolerated dose (MTD) or recommended phase 2 dose (RP2D).
This is a phase I, first-in-human study to evaluate the safety and tolerability of
      acapatamab; a half-life extended (HLE) bispecific T-cell engager (BiTE®) construct, alone and
      in combination with pembrolizumab, etanercept prophylaxis and cytochrome P450 (CYP)
      phenotyping cocktail in subjects with metastatic castration-resistant prostate cancer.
allocation: Non-Randomized
intervention model: Sequential Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Number of participants with dose-limiting toxicity
time frame: Up to 3 years
description: Parts 1, 2, 3, 4, 5, and 6 of the study
measure: Number of participants with treatment-emergent adverse events
time frame: Up to 3 years
description: Parts 1, 2, 3, 4, 5, and 6 of the study
measure: Number of participants with treatment-related adverse events
time frame: Up to 3 years
description: Parts 1, 2, 3, 4, 5, and 6 of the study
measure: Number of participants with clinically significant changes in vital signs
time frame: Up to 3 years
description: Parts 1, 2, 3, 4, 5, and 6 of the study
measure: Number of participants with clinically significant changes in electrocardiogram (ECG)
time frame: Up to 3 years
description: Parts 1, 2, 3, 4, 5, and 6 of the study
measure: Number of participants with clinically significant changes in clinical laboratory tests
time frame: Up to 3 years
description: Parts 1, 2, 3, 4, 5, and 6 of the study
measure: Maximum serum concentration (Cmax) of acapatamab
time frame: Up to 3 years
description: Parts 1, 2, 3, 4, 5, and 6 of the study
measure: Minimum serum concentration (Cmin) of acapatamab
time frame: Up to 3 years
description: Parts 1, 2, 3, 4, 5, and 6 of the study
measure: Area under the concentration-time curve (AUC) over the dosing interval of acapatamab
time frame: Up to 3 years
description: Parts 1, 2, 3, 4, 5, and 6 of the study
measure: Accumulation ratio of acapatamab
time frame: Up to 3 years
description: Parts 1, 2, 3, 4, 5, and 6 of the study
measure: Half-life of acapatamab
time frame: Up to 3 years
description: Parts 1, 2, 3, 4, 5, and 6 of the study
measure: Objective response (OR)
time frame: Up to 3 years
description: Parts 1, 2, 3, 4, 5, and 6 of the study
measure: Prostate-specific antigen (PSA) response
time frame: Up to 3 years
description: Parts 1, 2, 3, 4, 5, and 6 of the study
measure: Duration of response (DOR) (radiographic and PSA)
time frame: Up to 3 years
description: Parts 1, 2, 3, 4, 5, and 6 of the study
measure: Percentage of participants experiencing a response based on 68Gallium (68Ga)-prostate-specific membrane antigen (PSMA)-11 positron emission tomography (PET)/computed tomography (CT) response evaluations
time frame: Up to 3 years
description: Parts 1, 2 and 3 only.
measure: Percentage of participants experiencing a response based on 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) response evaluations
time frame: Up to 3 years
description: Parts 1, 2 and 3 only.
measure: Change in time to progression (radiographic and PSA)
time frame: Up to 3 years
description: Parts 1, 2, 3, 4, 5, and 6 of the study
measure: Progression-free survival (PFS) (radiographic and PSA)
time frame: Up to 3 years
description: Parts 1, 2, 3, 4, 5, and 6 of the study.
measure: 1, 2 and 3-year overall survival (OS)
time frame: Up to 3 years
description: Parts 1, 2, 3, 4, 5, and 6 of the study
measure: Percentage of participants experiencing circulating tumor cells (CTC) response
time frame: Up to 3 years
description: Parts 1, 2, 3, 4, 5, and 6 of the study. CTC response defined as CTC0 (reduction of CTCs > 0 to 0) or CTC conversion (≥ 5 CTCs/7.5 mL blood to ≤ 4 CTCs/7.5 mL blood)
measure: Other PCWG3-recommended endpoints - time to symptomatic skeletal events
time frame: Up to 3 years
description: Parts 1, 2, 3, 4, 5, and 6 of the study
measure: Other PCWG3-recommended endpoints - lactate dehydrogenase [LDH] levels
time frame: Up to 3 years
description: Parts 1, 2, 3, 4, 5, and 6 of the study
measure: Other PCWG3-recommended endpoints - hemoglobin levels
time frame: Up to 3 years
description: Parts 1, 2, 3, 4, 5, and 6 of the study
measure: Other PCWG3-recommended endpoints - neutrophil-to-lymphocyte ratio
time frame: Up to 3 years
description: Parts 1, 2, 3, 4, 5, and 6 of the study
measure: Other PCWG3-recommended endpoints - urine N-telopeptide levels
time frame: Up to 3 years
description: Parts 1, 2, 3, 4, 5, and 6 of the study
measure: Other PCWG3-recommended endpoints - alkaline phosphatase [total, bone] levels
time frame: Up to 3 years
description: Parts 1, 2, 3, 4, 5, and 6 of the study
measure: Maximum serum concentration (Cmax) of acapatamab when administered with CYP enzymes
time frame: Up to 3 years
description: Part 6 only.
measure: Area under the concentration-time curve over a 24-hour period (AUC24) of acapatamab when administered with CYP enzymes
time frame: Up to 3 years
description: Part 6 only.
measure: Half-life of acapatamab when administered with CYP enzymes
time frame: Up to 3 years
description: Part 6 only.
arm group label: Part 1 Dose-exploration: acapatamab treatment
arm group type: Experimental
description: Part 1 dose-exploration: acapatamab is administered intravenously. The dose-exploration phase of the study will estimate the MTD of acapatamab. RP2D may be identified based on emerging safety, efficacy, and pharmacodynamic data prior to reaching an MTD.
arm group label: Part 1 Dose-expansion: acapatamab treatment
arm group type: Experimental
description: Part 1 dose-expansion: acapatamab is administered intravenously at the MTD/RP2D.
arm group label: Part 2: acapatamab + Pembrolizumab
arm group type: Experimental
description: Part 2: acapatamab is administered intravenously at the MTD/RP2D. Pembrolizumab will be administered intravenously.
arm group label: Part 3: acapatamab + Etanercept Prophylaxis
arm group type: Experimental
description: Part 3: acapatamab is administered intravenously at RP2D/MTD levels. Etanercept will be administered subcutaneously in cycle 1 only.
arm group label: Part 4: acapatamab 24 Hour Monitoring
arm group type: Experimental
description: Part 4: acapatamab is administered intravenously at RP2D/MTD with 24-hour monitoring.
arm group label: Part 5: acapatamab Outpatient Cohort
arm group type: Experimental
description: Part 5: acapatamab is administered intravenously at RP2D/MTD in an outpatient setting with 8-hour monitoring.
arm group label: Part 6: acapatamab + Cytochrome P450 (CYP) Cocktail Drug Interaction
arm group type: Experimental
description: Part 6: acapatamab is administered intravenously at RP2D/MTD. A CYP phenotyping cocktail will be administered orally.
intervention type: Drug
intervention name: acapatamab
description: Investigational immunotherapy for the treatment of metastatic castration-resistant prostate cancer
arm group label: Part 1 Dose-expansion: acapatamab treatment
arm group label: Part 1 Dose-exploration: acapatamab treatment
arm group label: Part 2: acapatamab + Pembrolizumab
arm group label: Part 3: acapatamab + Etanercept Prophylaxis
arm group label: Part 4: acapatamab 24 Hour Monitoring
arm group label: Part 5: acapatamab Outpatient Cohort
arm group label: Part 6: acapatamab + Cytochrome P450 (CYP) Cocktail Drug Interaction
other name: PSMA Targeted Therapy
intervention type: Drug
intervention name: Pembrolizumab
description: Combined with acapatamab for investigational treatment of mCRPC
arm group label: Part 2: acapatamab + Pembrolizumab
other name: PD-1 inhibitor
intervention type: Drug
intervention name: Etanercept
description: Prophylaxis for acapatamab-related cytokine release syndrome.
arm group label: Part 3: acapatamab + Etanercept Prophylaxis
other name: TNF-alpha inhibitor
intervention type: Drug
intervention name: Cytochrome P450 (CYP) Cocktail
description: Evaluate the effect of co-administration of multiple dosing of acapatamab on plasma
arm group label: Part 6: acapatamab + Cytochrome P450 (CYP) Cocktail Drug Interaction
other name: Cooperstown 5+1 CYP phenotyping cocktail
criteria: 
gender: Male
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: MD
role: Study Director
affiliation: Amgen
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country: Australia
country: Austria
country: Belgium
country: Canada
country: France
country: Japan
country: Netherlands
country: Singapore
country: Taiwan
country: United States
url: http://www.amgentrials.com
description: AmgenTrials clinical trials website
responsible party type: Sponsor
mesh term: Prostatic Neoplasms
mesh term: Etanercept
mesh term: Pembrolizumab
mesh term: Immune Checkpoint Inhibitors
sharing ipd: Yes
ipd description: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd info type: Informed Consent Form (ICF)
ipd info type: Clinical Study Report (CSR)
ipd time frame: Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication (or other new use) have been granted marketing authorization in both the US and Europe, or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
ipd access criteria: Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors, and if not approved, may be further arbitrated by a Data Sharing Independent Review Panel. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the URL below.
ipd url: https://www.amgen.com/datasharing