<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/NCT03797391</url>
  </required_header>
  <id_info>
    <org_study_id>EMB01X101</org_study_id>
    <nct_id>NCT03797391</nct_id>
  </id_info>
  <brief_title>A Dose Escalation With Expansion Study of EMB-01 in Participants With Advanced/Metastatic Solid Tumors</brief_title>
  <official_title>First-in-human, Phase I/II, Multicenter, Open-Label Study of EMB-01 in Patients With Advanced/Metastatic Solid Tumors</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Shanghai EpimAb Biotherapeutics Co., Ltd.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Covance</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Shanghai EpimAb Biotherapeutics Co., Ltd.</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>
      First-in-human, Phase I/II, Multicenter, Open-Label Study of EMB-01 in Patients with&#xD;
      Advanced/Metastatic Solid Tumors&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a first-in-human (FIH), open-label, Phase I/II study of EMB-01, a bispecific&#xD;
      Epidermal growth factor receptor (EGFR) and c-Mesenchymal-Epithelial Transition (cMet)&#xD;
      antibody, in patients with advanced solid tumors who have progressed on available standard&#xD;
      therapies or for which no standard therapy exists. The study consists of two parts: Phase I&#xD;
      (dose escalation) and Phase II (cohort expansion). The study is planning to recruit&#xD;
      tentatively 33-66 subjects with advanced/metastatic solid tumors in phase I and approximately&#xD;
      42-120 subjects with EGFR mutant and/or cMET aberrated NSCLC who have progressed on or are&#xD;
      intolerant to standard treatment(s) (including platinum-based therapy) will be enrolled at&#xD;
      the RP2D(s) in phase II part of the study. In phase II, patients will be assigned to five&#xD;
      groups according to their molecular status at baseline. The trial will consist of molecular&#xD;
      pre-screening period (Phase II only), clinical screening period (-28 to -1 days), treatment&#xD;
      cycles (each cycle is 28 days, maximum up to 2 years), and safety follow-up period (30 days&#xD;
      after the last dose).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">December 13, 2018</start_date>
  <completion_date type="Anticipated">January 15, 2026</completion_date>
  <primary_completion_date type="Anticipated">March 14, 2025</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>N/A</allocation>
    <intervention_model>Sequential Assignment</intervention_model>
    <intervention_model_description>Dose escalation followed by Protocol at 100mg, 200mg, 350mg, 500mg, 700mg, 900mg, 1200mg, 1600mg, 2100mg, 2700mg and 3000mg .</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Maximum tolerated dose (MTD) (phase 1 only)</measure>
    <time_frame>cycle 1 (1cycle = 28 days)</time_frame>
    <description>Maximum tolerated dose</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Adverse Events (AEs), and Serious Adverse Events (SAEs)</measure>
    <time_frame>Screening up to follow-up (30 days after the last dose)</time_frame>
    <description>Adverse Events, and Serious Adverse Events</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Overall Response Rate (ORR) (phase 2 only)</measure>
    <time_frame>From the date fo dosing until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 48 months</time_frame>
    <description>Overall Response Rate</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Maximum Serum Concentration (Cmax)</measure>
    <time_frame>Through treatment discontinuation: an average of 6 months</time_frame>
    <description>Maximum Serum Concentration</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area Under the Plasma Concentration-Time Curve (AUC)</measure>
    <time_frame>Through treatment discontinuation: an average of 6 months</time_frame>
    <description>Area Under the Plasma Concentration-Time Curve</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Trough Serum Concentration (Ctrough)</measure>
    <time_frame>Through treatment discontinuation: an average of 6 months</time_frame>
    <description>Trough Serum Concentration</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Elimination half-life (t1/2)</measure>
    <time_frame>Through treatment discontinuation: an average of 6 months</time_frame>
    <description>Elimination half-life</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clearance (CL)</measure>
    <time_frame>Through treatment discontinuation: an average of 6 months</time_frame>
    <description>Clearance</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Volume of distribution at steady state (Vss)</measure>
    <time_frame>Through treatment discontinuation: an average of 6 months</time_frame>
    <description>volume of distribution at steady state</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Accumulation Ratio (AR)</measure>
    <time_frame>hrough treatment discontinuation: an average of 6 months</time_frame>
    <description>Accumulation Ratio</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Dose Proportionality</measure>
    <time_frame>Through treatment discontinuation: an average of 6 months</time_frame>
    <description>Dose Proportionality</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Anti-Drug Antibodies (ADA)</measure>
    <time_frame>Through study completion, an average of 7 months</time_frame>
    <description>Anti-Drug Antibodies</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration Of Response (DOR)</measure>
    <time_frame>From the date fo dosing until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 48 months</time_frame>
    <description>Duration Of Response</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression-Free Survival (PFS)</measure>
    <time_frame>Through treatment discontinuation: an average of 6 months</time_frame>
    <description>Progression-free survival</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Pharmacodynamic (Soluble EGFR and cMET concentration)</measure>
    <time_frame>Through treatment discontinuation: an average of 6 months</time_frame>
    <description>Pharmacodynamic (Soluble EGFR and cMET concentration)</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">186</enrollment>
  <condition>Neoplasms</condition>
  <condition>Neoplasm Metastasis</condition>
  <condition>Non-Small-Cell Lung Cancer</condition>
  <arm_group>
    <arm_group_label>Dose Escalation-Part 1, Expansion-Part 2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>In part 1, escalating dose cohort, patients will receive intravenous infusions of EMB-01 weekly (QW). The duration of each treatment cycle is 28 days (4 weeks). Dose escalation will continue until the maximum tolerated dose (MTD) or recommended phase II dose (RP2D) is reached or all planned doses are administered.&#xD;
In part 2, participants will receive intravenous infusion of EMB-01 at the recommended Phase II dose (RP2D) regimen(s) once weekly. The duration of each treatment cycle is 28 days (4 weeks).</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>EMB-01</intervention_name>
    <description>In part 1, patients will receive intravenous infusions of EMB01 weekly (QW). Dose escalation will continue until the maximum tolerated dose (MTD) or recommended phase II dose (RP2D) is reached or all planned doses are administered.&#xD;
In part 2, participants will receive intravenous infusion of EMB-01 at RP2D&#xD;
The duration of each treatment cycle in both part 1 and part 2 is 28 days (4 weeks).&#xD;
Participants may continue to receive study drug until discontinuation criteria are met.</description>
    <arm_group_label>Dose Escalation-Part 1, Expansion-Part 2</arm_group_label>
    <other_name>FIT-013a</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Molecular Pre-screening Inclusion criteria (Phase II only)&#xD;
&#xD;
          1. The patient must sign the molecular pre-screening Inform Consent to allow for the&#xD;
             molecular pre-screening process. All patients must have documented evidence of EGFR&#xD;
             and/or cMet aberrations.&#xD;
&#xD;
        Screening Inclusion Criteria&#xD;
&#xD;
          1. Able to understand and willing to sign the Informed Consent Form (ICF).&#xD;
&#xD;
          2. Histologically/cytologically confirmed advanced/metastatic solid tumors with&#xD;
             measurable disease [Response Evaluation Criteria in Solid Tumors (RECIST) v1.1]:&#xD;
&#xD;
             Phase I: advanced/metastatic solid tumors including but not limited to NSCLC,&#xD;
             colorectal cancer, gastric cancer and liver cancer refractory to standard therapy or&#xD;
             for which no standard therapy is available or accessible.&#xD;
&#xD;
             Phase II: Advanced/metastatic NSCLC Patients have confirmed EGFR mutant and/or cMET&#xD;
             aberration, and have progressed after standard treatment (including platinum-based&#xD;
             therapy) or are intolerant to standard treatment. Additionally, patients with T790M&#xD;
             mutation have received FDA/Health Authority approved therapies (if accessible) for&#xD;
             this indication (i.e., osimertinib) and have progressed or became intolerant.&#xD;
&#xD;
             A patient who has refused all currently available therapy is allowed to enroll, but&#xD;
             must be documented in the source record.&#xD;
&#xD;
          3. Must have adequate organ function.&#xD;
&#xD;
          4. Regarding prior anti-tumor therapy:&#xD;
&#xD;
               1. Must have stopped treatment at least 4 weeks or within 5 half-lives.&#xD;
&#xD;
               2. Generalized radiation therapy must have stopped 3 weeks before first dose of EMB&#xD;
                  01, or local radiotherapy or radiation therapy for bone metastases must have&#xD;
                  stopped 2 weeks before first dose of EMB-01. No therapeutic radiopharmaceuticals&#xD;
                  are taken within 8 weeks before first dose of EMB-01.&#xD;
&#xD;
               3. Patients must have recovered to ≤Grade 1 from the adverse effects of such above&#xD;
                  treatment before beginning study treatment.&#xD;
&#xD;
          5. Female patient with fertility or male patient whose partner has fertility should use&#xD;
             one or more contraceptive methods for contraception starting from screening period and&#xD;
             continue throughout the study treatment and for 3 months.&#xD;
&#xD;
          6. ECOG score 0 or 1 for phase I, and ≤2 for phase II.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Molecular Pre-screening Exclusion Criteria (Phase II only)&#xD;
&#xD;
        Subject who meets any of the follow criteria can't be proceeded to clinical screening:&#xD;
&#xD;
          1. Patients who are unwilling to sign the molecular pre-screening ICF.&#xD;
&#xD;
          2. Patients for whom local EGFR and/or cMET data or the results of central laboratory&#xD;
             testing do not meet the molecular pre-screening inclusion criteria.&#xD;
&#xD;
        Screening Exclusion Criteria&#xD;
&#xD;
          1. Life expectancy &lt; 3 months.&#xD;
&#xD;
          2. Subject with primacy central nervous system (CNS) malignancy or symptomatic CNS&#xD;
             (leptomeningeal or brain) metastases.&#xD;
&#xD;
          3. Pregnant or nursing females.&#xD;
&#xD;
          4. Subjects who have had major surgery within 28 days prior to screening.&#xD;
&#xD;
          5. Serious underlying medical conditions, including but not limited to un-controlled&#xD;
             hypertension, other cardiovascular disease or diabetes, ongoing or active infection,&#xD;
             psychiatric, psychological, familial or geographical condition that, in the judgment&#xD;
             of the investigator, may interfere the compliance with study treatment.&#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_contact>
    <last_name>Xiaodong Sun, MD</last_name>
    <phone>+86-21-61043299</phone>
    <email>xdsun@epimab.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Xuemei Xie</last_name>
    <phone>+86-21-61043299</phone>
    <email>xmxie@epimab.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Dana-Farber Cancer Institute</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02215</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Barbara Ann Karmanos Cancer Institute</name>
      <address>
        <city>Detroit</city>
        <state>Michigan</state>
        <zip>48201</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </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>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Guangdong General Hospital</name>
      <address>
        <city>Guangzhou</city>
        <state>Guang Dong</state>
        <zip>510080</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Shanghai Chest Hosptial</name>
      <address>
        <city>Shanghai</city>
        <state>Shanghai</state>
        <zip>200030</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location_countries>
    <country>China</country>
    <country>United States</country>
  </location_countries>
  <verification_date>May 2023</verification_date>
  <study_first_submitted>December 26, 2018</study_first_submitted>
  <study_first_submitted_qc>January 6, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 9, 2019</study_first_posted>
  <last_update_submitted>May 30, 2023</last_update_submitted>
  <last_update_submitted_qc>May 30, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">May 31, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Human Bispecific antibody,</keyword>
  <keyword>Epidermal Growth Factor Receptor (EGFR),</keyword>
  <keyword>c-Mesenchymal-Epithelial Transition (cMet),</keyword>
  <keyword>Neoplasms, Neoplasm Metastasis,</keyword>
  <keyword>Non-Small-Cell Lung Cancer (NSCLC), First-in-human,</keyword>
  <keyword>EMB-01, Tyrosine Kinase Inhibitor (TKI) Resistant</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Neoplasms</mesh_term>
    <mesh_term>Carcinoma, Non-Small-Cell Lung</mesh_term>
    <mesh_term>Neoplasm Metastasis</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/NCT03797391
org study id: EMB01X101
nct id: NCT03797391
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
First-in-human, Phase I/II, Multicenter, Open-Label Study of EMB-01 in Patients with
      Advanced/Metastatic Solid Tumors
This is a first-in-human (FIH), open-label, Phase I/II study of EMB-01, a bispecific
      Epidermal growth factor receptor (EGFR) and c-Mesenchymal-Epithelial Transition (cMet)
      antibody, in patients with advanced solid tumors who have progressed on available standard
      therapies or for which no standard therapy exists. The study consists of two parts: Phase I
      (dose escalation) and Phase II (cohort expansion). The study is planning to recruit
      tentatively 33-66 subjects with advanced/metastatic solid tumors in phase I and approximately
      42-120 subjects with EGFR mutant and/or cMET aberrated NSCLC who have progressed on or are
      intolerant to standard treatment(s) (including platinum-based therapy) will be enrolled at
      the RP2D(s) in phase II part of the study. In phase II, patients will be assigned to five
      groups according to their molecular status at baseline. The trial will consist of molecular
      pre-screening period (Phase II only), clinical screening period (-28 to -1 days), treatment
      cycles (each cycle is 28 days, maximum up to 2 years), and safety follow-up period (30 days
      after the last dose).
allocation: N/A
intervention model: Sequential Assignment
intervention model description: Dose escalation followed by Protocol at 100mg, 200mg, 350mg, 500mg, 700mg, 900mg, 1200mg, 1600mg, 2100mg, 2700mg and 3000mg .
primary purpose: Treatment
masking: None (Open Label)
measure: Maximum tolerated dose (MTD) (phase 1 only)
time frame: cycle 1 (1cycle = 28 days)
description: Maximum tolerated dose
measure: Adverse Events (AEs), and Serious Adverse Events (SAEs)
time frame: Screening up to follow-up (30 days after the last dose)
description: Adverse Events, and Serious Adverse Events
measure: Overall Response Rate (ORR) (phase 2 only)
time frame: From the date fo dosing until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 48 months
description: Overall Response Rate
measure: Maximum Serum Concentration (Cmax)
time frame: Through treatment discontinuation: an average of 6 months
description: Maximum Serum Concentration
measure: Area Under the Plasma Concentration-Time Curve (AUC)
time frame: Through treatment discontinuation: an average of 6 months
description: Area Under the Plasma Concentration-Time Curve
measure: Trough Serum Concentration (Ctrough)
time frame: Through treatment discontinuation: an average of 6 months
description: Trough Serum Concentration
measure: Elimination half-life (t1/2)
time frame: Through treatment discontinuation: an average of 6 months
description: Elimination half-life
measure: Clearance (CL)
time frame: Through treatment discontinuation: an average of 6 months
description: Clearance
measure: Volume of distribution at steady state (Vss)
time frame: Through treatment discontinuation: an average of 6 months
description: volume of distribution at steady state
measure: Accumulation Ratio (AR)
time frame: hrough treatment discontinuation: an average of 6 months
description: Accumulation Ratio
measure: Dose Proportionality
time frame: Through treatment discontinuation: an average of 6 months
description: Dose Proportionality
measure: Anti-Drug Antibodies (ADA)
time frame: Through study completion, an average of 7 months
description: Anti-Drug Antibodies
measure: Duration Of Response (DOR)
time frame: From the date fo dosing until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 48 months
description: Duration Of Response
measure: Progression-Free Survival (PFS)
time frame: Through treatment discontinuation: an average of 6 months
description: Progression-free survival
measure: Pharmacodynamic (Soluble EGFR and cMET concentration)
time frame: Through treatment discontinuation: an average of 6 months
description: Pharmacodynamic (Soluble EGFR and cMET concentration)
arm group label: Dose Escalation-Part 1, Expansion-Part 2
arm group type: Experimental
description: In part 1, escalating dose cohort, patients will receive intravenous infusions of EMB-01 weekly (QW). The duration of each treatment cycle is 28 days (4 weeks). Dose escalation will continue until the maximum tolerated dose (MTD) or recommended phase II dose (RP2D) is reached or all planned doses are administered.
In part 2, participants will receive intravenous infusion of EMB-01 at the recommended Phase II dose (RP2D) regimen(s) once weekly. The duration of each treatment cycle is 28 days (4 weeks).
intervention type: Drug
intervention name: EMB-01
description: In part 1, patients will receive intravenous infusions of EMB01 weekly (QW). Dose escalation will continue until the maximum tolerated dose (MTD) or recommended phase II dose (RP2D) is reached or all planned doses are administered.
In part 2, participants will receive intravenous infusion of EMB-01 at RP2D
The duration of each treatment cycle in both part 1 and part 2 is 28 days (4 weeks).
Participants may continue to receive study drug until discontinuation criteria are met.
arm group label: Dose Escalation-Part 1, Expansion-Part 2
other name: FIT-013a
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Xiaodong Sun, MD
phone: +86-21-61043299
email: xdsun@epimab.com
last name: Xuemei Xie
phone: +86-21-61043299
email: xmxie@epimab.com
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
country: China
country: United States
responsible party type: Sponsor
mesh term: Neoplasms
mesh term: Carcinoma, Non-Small-Cell Lung
mesh term: Neoplasm Metastasis
sharing ipd: No