<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/NCT03809013</url>
  </required_header>
  <id_info>
    <org_study_id>RC48-C009</org_study_id>
    <nct_id>NCT03809013</nct_id>
  </id_info>
  <brief_title>A Open-label, Single-arm, Multicenter, Phase II Study of RC48-ADC to Evaluate the Efficacy and Safety of Subjects With HER2 Overexpressing Locally Advanced or Metastatic Urothelial Cancer</brief_title>
  <official_title>A Open-label, Single-arm, Multicenter, Phase II Study of RC48-ADC to Evaluate the Efficacy and Safety of Subjects With HER2 Overexpressing Locally Advanced or Metastatic Urothelial Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>RemeGen Co., Ltd.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>RemeGen Co., Ltd.</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study will evaluate the efficacy and safety of intravenous RC48-ADC in patients with&#xD;
      HER2 overexpressing locally advanced or metastatic urothelial cancer.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Active, not recruiting</last_known_status>
  <start_date type="Actual">January 7, 2019</start_date>
  <completion_date type="Anticipated">December 31, 2022</completion_date>
  <primary_completion_date type="Actual">March 4, 2021</primary_completion_date>
  <phase>Phase 2</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>Objective Response Rate （ORR）as assessed by the Independent Review Committee</measure>
    <time_frame>24 months</time_frame>
    <description>Objective Response Rate was defined as the percentage of participants with a complete response (CR) or partial response (PR)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Objective Response Rate（ORR）as assessed by investigator</measure>
    <time_frame>24 months</time_frame>
    <description>Objective Response Rate was defined as the percentage of participants with a complete response (CR) or partial response (PR)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression Free Survival (PFS)</measure>
    <time_frame>24 months</time_frame>
    <description>PFS was defined as the time from the first administration of study treatment to the first occurrence of disease progression as determined by investigator using RECIST v1.1 or death from any cause, whichever comes first</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of Objective Response (DOR)</measure>
    <time_frame>24 months</time_frame>
    <description>DOR was defined as the time from first documented OR to first documented PD or death from any cause, whichever occurred earlier</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Disease control rate (DCR)</measure>
    <time_frame>24 months</time_frame>
    <description>DCR was defined as the percentage of participants with a complete response (CR), partial response (PR), or stable disease (SD)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival (OS)</measure>
    <time_frame>24 months</time_frame>
    <description>OS was defined as the time from the first administration of study treatment to death from any cause.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">60</enrollment>
  <condition>Urothelial Carcinoma</condition>
  <arm_group>
    <arm_group_label>RC48-ADC</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will be treated with RC48-ADC 2.0 mg/kg, once every 2 weeks (Q2W) until investigator-assessed loss of clinical benefit, unacceptable toxicity, investigator or participant's decision to withdraw from therapy, or death (whichever occurs first).</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>RC48-ADC</intervention_name>
    <description>2.0mg/kg IV every 2 weeks</description>
    <arm_group_label>RC48-ADC</arm_group_label>
    <other_name>Recombinant Humanized anti-HER2 Monoclonal Antibody-MMAE Conjugate For Injection</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Voluntary agreement to provide written informed consent.&#xD;
&#xD;
          -  Male or female, Age ≥ 18 years.&#xD;
&#xD;
          -  Predicted survival ≥ 12 weeks.&#xD;
&#xD;
          -  Diagnosed with histologically or cytologically-confirmed locally advanced or&#xD;
             metastatic urothelial cancer, originate from bladder, renal pelvis, ureter and urinary&#xD;
             tract.&#xD;
&#xD;
          -  Unresectable or disease progression (i.e. locally advanced/metastasis) after surgery&#xD;
             and at least regular chemotherapy including gemcitabine,cisplatin AND paclitaxel.&#xD;
             Disease progression within 6 months of the completion of neo-adjuvant and adjuvant&#xD;
             chemotherapy with gemcitabine, cisplatin AND paclitaxel is also eligible.&#xD;
&#xD;
          -  Measurable lesion according to RECIST 1.1.&#xD;
&#xD;
          -  HER2 overexpressing (i.e. IHC 2+ or 3+) as confirmed by the central lab. Primary or&#xD;
             metastatic tumor sample will be provided for HER2 test.&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1.&#xD;
&#xD;
          -  Adequate organ function, evidenced by the following laboratory results within 7 days&#xD;
             prior to the study treatment:&#xD;
&#xD;
        Cardiac ejection fraction ≥ 50 %. Hemoglobin ≥ 9g/dL; Absolute neutrophil count ≥ 1.5×109&#xD;
        /L Platelets ≥ 100×109 /L; Total bilirubin ≤ 1.5× ULN; AST and ALT ≤ 2.5×ULN and ≤ 5 × ULN&#xD;
        with hepatic metastasis; Serum creatinine ≤1.5×ULN.&#xD;
&#xD;
          -  All female subjects will be considered to be of child-bearing potential unless they&#xD;
             are postmenopausal, or have been sterilized surgically.Female subjects of&#xD;
             child-bearing potential must agree to use two forms of highly effective contraception.&#xD;
             Male subjects and their female partner who are of child-bearing potential must agree&#xD;
             to use two forms of highly effective contraception.&#xD;
&#xD;
          -  Willing to adhere to the study visit schedule and the prohibitions and restrictions&#xD;
             specified in this protocol.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Known hypersensitivity to the components of Recombinant Humanized Anti-HER2 Monoclonal&#xD;
             Antibody-MMAE Conjugate.&#xD;
&#xD;
          -  Toxicity of previous anti-tumor treatment not recovered to CTCAE Grade 0-1 (with&#xD;
             exception of Grade 2 alopecia).&#xD;
&#xD;
          -  Pleural or abdominal effusion with clinical symptoms that requires ongoing treatment.&#xD;
&#xD;
          -  History of major surgery within 4 weeks of planned start of trial treatment.&#xD;
&#xD;
          -  Has received a live virus vaccine within 4 weeks of planned start of trial treatment.&#xD;
&#xD;
          -  Currently known active infection with HIV or tuberculosis.&#xD;
&#xD;
          -  Diagnosed with HBsAg, HBcAb positive and HBV DNA copy positive, or HCVAb positive.&#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;
          -  History of other malignancy within the previous 5 years, except for appropriately&#xD;
             treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, or cancers with&#xD;
             a similar curative outcome as those mentioned above.&#xD;
&#xD;
          -  known central nervous system metastases.&#xD;
&#xD;
          -  Uncontrolled hypertension, diabetes, Interstitial lung Disease, or COPD;&#xD;
&#xD;
          -  Treated with systemic treatment (e.g. immunomodulators, corticosteroids or&#xD;
             immunosuppressants) for the autoimmune disease within 2 years prior to the study&#xD;
             treatment.&#xD;
&#xD;
          -  NYHA Class III heart failure.&#xD;
&#xD;
          -  Pregnancy or lactation.&#xD;
&#xD;
          -  Assessed by the investigator to be unable or unwilling to comply with the requirements&#xD;
             of the protocol.&#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>Jun Guo, Ph.D</last_name>
    <role>Principal Investigator</role>
    <affiliation>Peking University Cancer Hospital &amp; Institute</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Anhui Cancer Hospital</name>
      <address>
        <city>Hefei</city>
        <state>Anhui</state>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Beijing Cancer Hospital</name>
      <address>
        <city>Beijing</city>
        <state>Beijing</state>
        <zip>100078</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cancer Hospital Chinese Academy of Medical Sciences</name>
      <address>
        <city>Beijing</city>
        <state>Beijing</state>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Peking University First Hospital</name>
      <address>
        <city>Beijing</city>
        <state>Beijing</state>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sun Yat-sen University Cancer Center</name>
      <address>
        <city>Guangzhou</city>
        <state>Guangdong</state>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hunan Cancer Hospital</name>
      <address>
        <city>Changsha</city>
        <state>Hunan</state>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Qilu Hospital of Shandong University</name>
      <address>
        <city>Jinan</city>
        <state>Shandong</state>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>West China Hospital</name>
      <address>
        <city>Chendu</city>
        <state>Sichuan</state>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>September 2021</verification_date>
  <study_first_submitted>January 16, 2019</study_first_submitted>
  <study_first_submitted_qc>January 16, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 18, 2019</study_first_posted>
  <last_update_submitted>February 20, 2022</last_update_submitted>
  <last_update_submitted_qc>February 20, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">February 22, 2022</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, Transitional Cell</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Trastuzumab</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</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/NCT03809013
org study id: RC48-C009
nct id: NCT03809013
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
This study will evaluate the efficacy and safety of intravenous RC48-ADC in patients with
      HER2 overexpressing locally advanced or metastatic urothelial cancer.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Objective Response Rate （ORR）as assessed by the Independent Review Committee
time frame: 24 months
description: Objective Response Rate was defined as the percentage of participants with a complete response (CR) or partial response (PR)
measure: Objective Response Rate（ORR）as assessed by investigator
time frame: 24 months
description: Objective Response Rate was defined as the percentage of participants with a complete response (CR) or partial response (PR)
measure: Progression Free Survival (PFS)
time frame: 24 months
description: PFS was defined as the time from the first administration of study treatment to the first occurrence of disease progression as determined by investigator using RECIST v1.1 or death from any cause, whichever comes first
measure: Duration of Objective Response (DOR)
time frame: 24 months
description: DOR was defined as the time from first documented OR to first documented PD or death from any cause, whichever occurred earlier
measure: Disease control rate (DCR)
time frame: 24 months
description: DCR was defined as the percentage of participants with a complete response (CR), partial response (PR), or stable disease (SD)
measure: Overall survival (OS)
time frame: 24 months
description: OS was defined as the time from the first administration of study treatment to death from any cause.
arm group label: RC48-ADC
arm group type: Experimental
description: Participants will be treated with RC48-ADC 2.0 mg/kg, once every 2 weeks (Q2W) until investigator-assessed loss of clinical benefit, unacceptable toxicity, investigator or participant's decision to withdraw from therapy, or death (whichever occurs first).
intervention type: Drug
intervention name: RC48-ADC
description: 2.0mg/kg IV every 2 weeks
arm group label: RC48-ADC
other name: Recombinant Humanized anti-HER2 Monoclonal Antibody-MMAE Conjugate For Injection
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Jun Guo, Ph.D
role: Principal Investigator
affiliation: Peking University Cancer Hospital & Institute
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: China
responsible party type: Sponsor
mesh term: Carcinoma, Transitional Cell
mesh term: Trastuzumab
sharing ipd: Undecided