<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/NCT04492488</url>
  </required_header>
  <id_info>
    <org_study_id>MRG002-101</org_study_id>
    <nct_id>NCT04492488</nct_id>
  </id_info>
  <brief_title>A Study of MRG002 in Patients With HER2-Positive Advanced Solid Tumors and Locally Advanced or Metastatic Gastric/Gastroesophageal Junction (GEJ) Cancer</brief_title>
  <official_title>An Open-Label, Multi-center Phase I/II Dose Escalation and Expansion Study to Assess the Safety, Efficacy and Pharmacokinetics of MRG002 in Patients With HER2-Positive Advanced Solid Tumors and Locally Advanced or Metastatic Gastric/Gastroesophageal Junction (GEJ) Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Shanghai Miracogen Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Shanghai Miracogen Inc.</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>
      The objective of this study is to assess the safety, efficacy, and pharmacokinetics of&#xD;
      MRG002, as well as the immunogenicity as defined by the incidence of anti-drug antibody (ADA)&#xD;
      of MRG002 in patients with HER2-positive advanced solid tumors and locally advanced or&#xD;
      metastatic gastric/gastroesophageal junction (GEJ) cancer.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study consists of two parts. In Part A, patients will receive MRG002 as a monotherapy at&#xD;
      doses of 2.2 or 2.6 mg/kg intravenously (IV) over 60-90 minute on Day 1 of every 3 weeks&#xD;
      (Q3W), to determine the maximum tolerated dose (MTD) and recommended phase II dose (RP2D). In&#xD;
      part B, patients will receive a single IV infusion of MRG002 at RP2D on Day 1 of Q3W.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">May 24, 2021</start_date>
  <completion_date type="Anticipated">August 2023</completion_date>
  <primary_completion_date type="Anticipated">December 2022</primary_completion_date>
  <phase>Phase 1/Phase 2</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>Maximum Tolerated Dose (MTD)</measure>
    <time_frame>DLT will be evaluated during the first 21-day treatment cycle (Cycle 1)</time_frame>
    <description>The dose level in which (i) less than 2 out of 6 patients in a treatment cohort experiences dose-limiting toxicity (DLT); or (ii) &lt;33% of an evaluable patient treatment cohort experiences DLT.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Recommended Phase II Dose (RP2D)</measure>
    <time_frame>Day 1 to Day 21 of Cycle 1</time_frame>
    <description>Identify the recommended Phase II dose (RP2D) of MRG002 for Phase II clinical study. The RP2D may be the same as the MTD or an evaluable dose level lower than the MTD.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Objective Response Rate (ORR)</measure>
    <time_frame>Baseline to study completion (24 months)</time_frame>
    <description>Objective response rate (ORR) will be assessed by Independent Central Review (ICR) based on RECIST v1.1. Cumulative safety and dosing data will be reviewed by an independent Data Safety Monitoring Board (DSMB).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidence of Adverse Events (AEs)</measure>
    <time_frame>After signing informed consent until 45 days after the last dose of MRG002</time_frame>
    <description>AEs will be coded using MedDAR. Descriptive statistics will be used to summarize results to assess the safety and tolerability profile of MRG002.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Duration of Response (DoR)</measure>
    <time_frame>Baseline to study completion (24 months)</time_frame>
    <description>Sensitivity analyses of DoR from the Investigator's assessment will be performed in the final analysis.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Disease Control Rate (DCR)</measure>
    <time_frame>Baseline to study completion (24 months)</time_frame>
    <description>Sensitivity analyses of DCR from the Investigator's assessment will be performed in the final analysis.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression Free Survival (PFS)</measure>
    <time_frame>Baseline to study completion (24 months)</time_frame>
    <description>Sensitivity analyses of PFS from the Investigator's assessment will be performed in the final analysis.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics (PK) parameter for MRG002: Maximum Drug Concentration (Cmax)</measure>
    <time_frame>Baseline to study completion (24 months)</time_frame>
    <description>Cmax will be derived from the PK blood samples collected and will be summarized with descriptive statistics.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PK parameter for MRG002: Area Under the Curve Up to the Last Validated Measurable Plasma Concentration (AUClast)</measure>
    <time_frame>Baseline to study completion (24 months)</time_frame>
    <description>AUClast will be derived from the PK blood samples collected and will be summarized with descriptive statistics.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PK parameter for total antibody (TAb): Cmax</measure>
    <time_frame>Baseline to study completion (24 months)</time_frame>
    <description>Cmax will be derived from the PK blood samples collected and will be summarized with descriptive statistics.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PK parameter for TAb: AUClast</measure>
    <time_frame>Baseline to study completion (24 months)</time_frame>
    <description>AUClast will be derived from the PK blood samples collected and will be summarized with descriptive statistics.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PK parameter for Monomethyl Auristatin E (MMAE): Cmax</measure>
    <time_frame>Baseline to study completion (24 months)</time_frame>
    <description>Cmax will be derived from the PK blood samples collected and will be summarized with descriptive statistics.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PK parameter for MMAE: AUClast</measure>
    <time_frame>Baseline to study completion (24 months)</time_frame>
    <description>AUClast will be derived from the PK blood samples collected and will be summarized with descriptive statistics.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Immunogenicity</measure>
    <time_frame>Baseline to study completion (24 months)</time_frame>
    <description>5 mL Blood samples for anti-drug antibody (ADA) analysis will be collected each time according to the pre-defined timepoints. The incidence of ADA will be summarized for all patients who received at least one administration of MRG002.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">129</enrollment>
  <condition>Advanced Solid Tumors</condition>
  <condition>Advanced or Metastatic Gastric Cancer</condition>
  <condition>Advanced or Metastatic Gastroesophageal Junction Cancer</condition>
  <arm_group>
    <arm_group_label>Solid Tumors</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Phase I Dose Escalation: MRG002 will be administrated by an IV infusion of escalating doses (starting dose of 2.2 mg/kg, followed by 2.6 mg/kg) on Day 1 of every 3 weeks (21-day cycle).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Locally Advanced or Metastatic Gastric/GEJ Cancer</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>MRG002 will be administrated by an IV infusion on Day 1 of every 3 weeks (21-day cycle).</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>MRG002</intervention_name>
    <description>Administrated intravenously</description>
    <arm_group_label>Locally Advanced or Metastatic Gastric/GEJ Cancer</arm_group_label>
    <arm_group_label>Solid Tumors</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  The patient must be able to provide written informed consent and follow the&#xD;
             requirements specified in protocol.&#xD;
&#xD;
          -  Age: ≥18 years.&#xD;
&#xD;
          -  Life expectancy ≥6 months.&#xD;
&#xD;
          -  Must have histologically or cytologically confirmed HER2-positive metastatic,&#xD;
             unresectable cancer and must have had prior disease progression on all standard&#xD;
             therapies for their tumor.&#xD;
&#xD;
          -  Available archival tumor tissue (archival or from a new biopsy).&#xD;
&#xD;
          -  At least one non-irradiated measurable tumor lesion according to RECIST v1.1.&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.&#xD;
&#xD;
          -  Acceptable liver, renal, hematologic and coagulation function.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Toxicities (except alopecia &amp; fatigue) due to prior antitumor therapy are higher than&#xD;
             CTCAE v5.0 Grade 1.&#xD;
&#xD;
          -  Toxicities due to radiotherapy (higher than grade 1) have not resolved to CTCAE v5.0&#xD;
             Grade ≤1 at least 21 days prior to the screening visit.&#xD;
&#xD;
          -  Prior palliative or therapeutic radiation therapy to any RECIST v1.1 target lesion&#xD;
             that defines baseline measurable disease for the study.&#xD;
&#xD;
          -  Untreated or uncontrolled central nervous system (CNS) metastases.&#xD;
&#xD;
          -  Any chemotherapy, biotherapy, immunotherapy, radiotherapy or other anti-tumor therapy&#xD;
             within 3 weeks of the first dose of study treatment.&#xD;
&#xD;
          -  Any severe cardiac dysfunction within 6 months of enrollment.&#xD;
&#xD;
          -  Pulmonary embolism or deep vein thrombosis within 3 months prior to the first dose of&#xD;
             study drug.&#xD;
&#xD;
          -  Concurrent malignancy within 5 years prior to entry.&#xD;
&#xD;
          -  Uncontrolled hypertension (systolic blood pressure &gt;160 mmHg or diastolic blood&#xD;
             pressure &gt; 100 mmHg).&#xD;
&#xD;
          -  History of ventricular tachycardia, or torsade des pointes.&#xD;
&#xD;
          -  History of moderate to severe dyspnea at rest due to advanced malignancies or their&#xD;
             complications, severe primary lung disease, current need of continuous oxygen therapy,&#xD;
             or clinically active interstitial lung disease (ILD) or pneumonitis.&#xD;
&#xD;
          -  Major surgery within 4 weeks of the first dose of study treatment and not fully&#xD;
             recovered. Minor surgery within 2 weeks prior to study treatment.&#xD;
&#xD;
          -  Known allergic reactions to any component or excipient of MRG002 or known allergic&#xD;
             reactions to trastuzumab or other prior anti-HER2 or other monoclonal antibody ≥ Grade&#xD;
             3.&#xD;
&#xD;
          -  Patients who have any known liver disease, including chronic hepatitis B, hepatitis C,&#xD;
             autoimmune hepatic disorders, primary biliary cirrhosis or sclerosing cholangitis;&#xD;
             Patients who have concurrent, serious, uncontrolled infections or known infection with&#xD;
             HIV, or have a diagnosed acquired immunodeficiency syndrome (AIDS); or an uncontrolled&#xD;
             autoimmune disease, or have undergone organ transplant.&#xD;
&#xD;
          -  Active uncontrolled bacterial, viral, fungal, rickettsial, or parasitic infection.&#xD;
&#xD;
          -  Any severe and/or uncontrolled systemic disease that at the discretion of investigator&#xD;
             and sponsor makes it undesirable for the patient to participate in this study.&#xD;
&#xD;
          -  Use of systemic corticosteroids within 4 weeks prior to the first dose of treatment.&#xD;
&#xD;
          -  Use of strong CYP3A4 inhibitors.&#xD;
&#xD;
          -  Pregnancy or breast-feeding.&#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>Crystal Denlinger, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Fox Chase Cancer Center</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Jenny Y Li, RPh</last_name>
    <phone>650-237-9339</phone>
    <email>jenny_li@innucubebio.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Rakesh H Nandan, MBBS, MPH</last_name>
    <phone>18574136404</phone>
    <email>rakesh.nandan@wuxiapptec.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>University of California Irvine Chao Family Comprehensive Cancer Center</name>
      <address>
        <city>Orange</city>
        <state>California</state>
        <zip>92868</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Farshid Dayyani, MD. PhD</last_name>
      <phone>714-456-8161</phone>
      <email>fdayyani@hs.uci.edu</email>
    </contact>
    <contact_backup>
      <last_name>Carmen Lu</last_name>
      <phone>714-456-8442</phone>
      <email>carmenml@hs.uci.edu</email>
    </contact_backup>
  </location>
  <location>
    <facility>
      <name>Gabrail Cancer Center Research</name>
      <address>
        <city>Canton</city>
        <state>Ohio</state>
        <zip>44718</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Withdrawn</status>
  </location>
  <location>
    <facility>
      <name>Cleveland Clinic Taussig Cancer Center</name>
      <address>
        <city>Cleveland</city>
        <state>Ohio</state>
        <zip>44915</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Withdrawn</status>
  </location>
  <location>
    <facility>
      <name>Fox Chase Cancer Center</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19111</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Withdrawn</status>
  </location>
  <location>
    <facility>
      <name>Prisma Health Care Institute</name>
      <address>
        <city>Greenville</city>
        <state>South Carolina</state>
        <zip>29605</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Withdrawn</status>
  </location>
  <location>
    <facility>
      <name>MD Anderson Cancer Center</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77040</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jaffer Ajani</last_name>
      <phone>713-792-2828</phone>
      <email>jajani@mdanderson.org</email>
    </contact>
    <contact_backup>
      <last_name>Jackie Smith</last_name>
      <email>JSmith19@mdanderson.org</email>
    </contact_backup>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>March 2022</verification_date>
  <study_first_submitted>July 23, 2020</study_first_submitted>
  <study_first_submitted_qc>July 27, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 30, 2020</study_first_posted>
  <last_update_submitted>May 4, 2022</last_update_submitted>
  <last_update_submitted_qc>May 4, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">May 6, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>MRG002</keyword>
  <keyword>Antibody Drug Conjugate (ADC)</keyword>
  <keyword>HER2</keyword>
  <keyword>Solid tumors</keyword>
  <keyword>Gastric/GEJ Cancer</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Neoplasms</mesh_term>
  </condition_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/NCT04492488
org study id: MRG002-101
nct id: NCT04492488
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
The objective of this study is to assess the safety, efficacy, and pharmacokinetics of
      MRG002, as well as the immunogenicity as defined by the incidence of anti-drug antibody (ADA)
      of MRG002 in patients with HER2-positive advanced solid tumors and locally advanced or
      metastatic gastric/gastroesophageal junction (GEJ) cancer.
This study consists of two parts. In Part A, patients will receive MRG002 as a monotherapy at
      doses of 2.2 or 2.6 mg/kg intravenously (IV) over 60-90 minute on Day 1 of every 3 weeks
      (Q3W), to determine the maximum tolerated dose (MTD) and recommended phase II dose (RP2D). In
      part B, patients will receive a single IV infusion of MRG002 at RP2D on Day 1 of Q3W.
allocation: Non-Randomized
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Maximum Tolerated Dose (MTD)
time frame: DLT will be evaluated during the first 21-day treatment cycle (Cycle 1)
description: The dose level in which (i) less than 2 out of 6 patients in a treatment cohort experiences dose-limiting toxicity (DLT); or (ii) <33% of an evaluable patient treatment cohort experiences DLT.
measure: Recommended Phase II Dose (RP2D)
time frame: Day 1 to Day 21 of Cycle 1
description: Identify the recommended Phase II dose (RP2D) of MRG002 for Phase II clinical study. The RP2D may be the same as the MTD or an evaluable dose level lower than the MTD.
measure: Objective Response Rate (ORR)
time frame: Baseline to study completion (24 months)
description: Objective response rate (ORR) will be assessed by Independent Central Review (ICR) based on RECIST v1.1. Cumulative safety and dosing data will be reviewed by an independent Data Safety Monitoring Board (DSMB).
measure: Incidence of Adverse Events (AEs)
time frame: After signing informed consent until 45 days after the last dose of MRG002
description: AEs will be coded using MedDAR. Descriptive statistics will be used to summarize results to assess the safety and tolerability profile of MRG002.
measure: Duration of Response (DoR)
time frame: Baseline to study completion (24 months)
description: Sensitivity analyses of DoR from the Investigator's assessment will be performed in the final analysis.
measure: Disease Control Rate (DCR)
time frame: Baseline to study completion (24 months)
description: Sensitivity analyses of DCR from the Investigator's assessment will be performed in the final analysis.
measure: Progression Free Survival (PFS)
time frame: Baseline to study completion (24 months)
description: Sensitivity analyses of PFS from the Investigator's assessment will be performed in the final analysis.
measure: Pharmacokinetics (PK) parameter for MRG002: Maximum Drug Concentration (Cmax)
time frame: Baseline to study completion (24 months)
description: Cmax will be derived from the PK blood samples collected and will be summarized with descriptive statistics.
measure: PK parameter for MRG002: Area Under the Curve Up to the Last Validated Measurable Plasma Concentration (AUClast)
time frame: Baseline to study completion (24 months)
description: AUClast will be derived from the PK blood samples collected and will be summarized with descriptive statistics.
measure: PK parameter for total antibody (TAb): Cmax
time frame: Baseline to study completion (24 months)
description: Cmax will be derived from the PK blood samples collected and will be summarized with descriptive statistics.
measure: PK parameter for TAb: AUClast
time frame: Baseline to study completion (24 months)
description: AUClast will be derived from the PK blood samples collected and will be summarized with descriptive statistics.
measure: PK parameter for Monomethyl Auristatin E (MMAE): Cmax
time frame: Baseline to study completion (24 months)
description: Cmax will be derived from the PK blood samples collected and will be summarized with descriptive statistics.
measure: PK parameter for MMAE: AUClast
time frame: Baseline to study completion (24 months)
description: AUClast will be derived from the PK blood samples collected and will be summarized with descriptive statistics.
measure: Immunogenicity
time frame: Baseline to study completion (24 months)
description: 5 mL Blood samples for anti-drug antibody (ADA) analysis will be collected each time according to the pre-defined timepoints. The incidence of ADA will be summarized for all patients who received at least one administration of MRG002.
arm group label: Solid Tumors
arm group type: Experimental
description: Phase I Dose Escalation: MRG002 will be administrated by an IV infusion of escalating doses (starting dose of 2.2 mg/kg, followed by 2.6 mg/kg) on Day 1 of every 3 weeks (21-day cycle).
arm group label: Locally Advanced or Metastatic Gastric/GEJ Cancer
arm group type: Experimental
description: MRG002 will be administrated by an IV infusion on Day 1 of every 3 weeks (21-day cycle).
intervention type: Drug
intervention name: MRG002
description: Administrated intravenously
arm group label: Locally Advanced or Metastatic Gastric/GEJ Cancer
arm group label: Solid Tumors
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Crystal Denlinger, MD
role: Principal Investigator
affiliation: Fox Chase Cancer Center
last name: Jenny Y Li, RPh
phone: 650-237-9339
email: jenny_li@innucubebio.com
last name: Rakesh H Nandan, MBBS, MPH
phone: 18574136404
email: rakesh.nandan@wuxiapptec.com
facility: 
status: Recruiting
contact: 
contact backup: 
facility: 
status: Withdrawn
facility: 
status: Withdrawn
facility: 
status: Withdrawn
facility: 
status: Withdrawn
facility: 
status: Recruiting
contact: 
contact backup: 
country: United States
responsible party type: Sponsor
mesh term: Neoplasms
sharing ipd: No