<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/NCT04441099</url>
  </required_header>
  <id_info>
    <org_study_id>NBE-002-01</org_study_id>
    <nct_id>NCT04441099</nct_id>
  </id_info>
  <brief_title>NBE-002 in Patients With Advanced Solid Tumors</brief_title>
  <official_title>A First-in-Human, Phase 1/2 Study of NBE-002, an Anti-ROR1 Antibody Drug Conjugate, in Patients With Advanced Solid Tumors</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>NBE-Therapeutics AG</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Cmed Clinical Services</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>NBE-Therapeutics AG</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>
      This first-in-human study will evaluate the recommended dose for further clinical&#xD;
      development, safety, tolerability, anti-tumor activity, immunogenicity, pharmacokinetics and&#xD;
      pharmacodynamics of NBE-002, a novel anti-ROR1 antibody-drug conjugate, in patients with&#xD;
      advanced solid tumors.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    End of Program&#xD;
  </why_stopped>
  <start_date type="Actual">June 19, 2020</start_date>
  <completion_date type="Actual">August 14, 2023</completion_date>
  <primary_completion_date type="Actual">August 14, 2023</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>Sequential Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Recommended Phase 2 Dose (RP2D) (Phase 1)</measure>
    <time_frame>Up to 48 months</time_frame>
    <description>The RP2D will be determined using dose limiting toxicities (DLTs) and all other available study data</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Anti-tumor Activity (Phase 2)</measure>
    <time_frame>Up to 60 months</time_frame>
    <description>Anti-tumor activity will be assessed by Response Evaluation Criteria in Solid Tumours (RECIST) v1.1</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Incidence of Adverse Events (Safety and Tolerability)</measure>
    <time_frame>Up to 60 months</time_frame>
    <description>Safety and tolerability profile will be assessed by Common Terminology Criteria for Adverse Events v5.0 and summarized by type, frequency, and severity of adverse events</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Preliminary Anti-tumor Activity (Phase 1)</measure>
    <time_frame>Up to 48 months</time_frame>
    <description>Preliminary anti-tumor activity will be assessed by Response Evaluation Criteria in Solid Tumours (RECIST) v1.1</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Concentrations of NBE-002</measure>
    <time_frame>Up to 60 months</time_frame>
    <description>Pharmacokinetic profile will be characterized by concentrations of NBE-002</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Concentrations of NBE-002-reactive antibodies</measure>
    <time_frame>Up to 60 months</time_frame>
    <description>Immunogenicity profile will be characterized by concentrations of NBE-002-reactive antibodies</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">12</enrollment>
  <condition>Advanced Solid Tumor</condition>
  <condition>Advanced Cancer</condition>
  <condition>Triple Negative Breast Cancer</condition>
  <arm_group>
    <arm_group_label>Dose-escalation Cohort (DEC)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Escalating doses of NBE-002 depending on cohort at enrollment.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Safety-expansion Cohort (SEC)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Dose to be determined based on DEC.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Expansion Cohort 1 (EC1)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Dose to be determined based on DEC and SEC.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Expansion Cohort 2 (EC2)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Dose to be determined based on DEC and SEC.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>NBE-002</intervention_name>
    <description>NBE-002 will be given intravenously on Day 1 of repeated 28-day cycles.</description>
    <arm_group_label>Dose-escalation Cohort (DEC)</arm_group_label>
    <arm_group_label>Expansion Cohort 1 (EC1)</arm_group_label>
    <arm_group_label>Expansion Cohort 2 (EC2)</arm_group_label>
    <arm_group_label>Safety-expansion Cohort (SEC)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Written informed consent&#xD;
&#xD;
          -  Age ≥18 years&#xD;
&#xD;
          -  Phase 1, DEC and SEC: patients with histologically or cytologically confirmed advanced&#xD;
             solid tumor (carcinoma or sarcoma), who have progressive disease, have undergone&#xD;
             systemic therapy for advanced disease, and for whom no standard therapy is available&#xD;
&#xD;
          -  Phase 2, EC1: patients with histologically or cytologically confirmed advanced&#xD;
             triple-negative breast cancer, who have progressive disease, and have undergone no&#xD;
             more than three prior lines of systemic therapy for advanced disease&#xD;
&#xD;
          -  Phase 2, EC2: patients with histologically or cytologically confirmed advanced solid&#xD;
             tumor (carcinoma or sarcoma) other than TNBC, who have progressive disease, and have&#xD;
             undergone no more than three prior lines of systemic therapy for advanced disease&#xD;
&#xD;
          -  Availability of pretreatment tumor tissue&#xD;
&#xD;
          -  Phase 1, DEC and SEC: at least one measurable or non-measurable lesion as per RECIST&#xD;
             v1.1&#xD;
&#xD;
          -  Phase 2, EC1 and EC2: at least one measurable lesion as per RECIST v1.1&#xD;
&#xD;
          -  Phase 1, DEC and SEC: Eastern Cooperative Oncology Group (ECOG) performance status of&#xD;
             0, 1 or 2&#xD;
&#xD;
          -  Phase 2, EC1 and EC2: ECOG performance status of 0 or 1&#xD;
&#xD;
          -  Adequate function of bone marrow, liver, kidneys, heart; adequate coagulation profile&#xD;
&#xD;
          -  Both male and female patients must agree to use effective contraceptive methods&#xD;
&#xD;
          -  Women of child-bearing potential (WCBP) must have a negative serum pregnancy test&#xD;
&#xD;
          -  Patients must be willing and able to sign the informed consent form, and to adhere to&#xD;
             the study visit schedule and other protocol requirements&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Prior treatment with any agent targeting ROR1&#xD;
&#xD;
          -  Presence of active central nervous system (CNS) metastasis&#xD;
&#xD;
          -  Persistent toxicities from previous systemic anti-neoplastic treatments of Grade &gt; 1&#xD;
             (or Grade &gt; 2 for neurotoxicity)&#xD;
&#xD;
          -  Systemic anti-neoplastic therapy within five half-lives or four weeks (six weeks for&#xD;
             nitrosourea and mitomycin-C), whichever is shorter, prior to first dose of the study&#xD;
             drug&#xD;
&#xD;
          -  Wide-field radiotherapy within four weeks, or focal radiation for analgesic purpose or&#xD;
             for lytic lesions at risk of fracture within two weeks prior to first dose of the&#xD;
             study drug, or no recovery from side effects of such intervention&#xD;
&#xD;
          -  Major surgery within four weeks prior to first dose of the study drug, or no recovery&#xD;
             from side effects of such intervention&#xD;
&#xD;
          -  Prior allogeneic bone marrow transplantation&#xD;
&#xD;
          -  Significant cardiac disease&#xD;
&#xD;
          -  History of thromboembolic or cerebrovascular events within six months prior to first&#xD;
             dose of the study drug&#xD;
&#xD;
          -  Acute and/or clinically significant bacterial, fungal or viral infection&#xD;
&#xD;
          -  Concomitant use of systemic steroids at dose of &gt;10 mg of prednisone or its equivalent&#xD;
             per day&#xD;
&#xD;
          -  Concurrent participation in another investigational clinical trial&#xD;
&#xD;
          -  Pregnant or breast-feeding females&#xD;
&#xD;
          -  Other conditions that prevent the patient from giving informed consent or&#xD;
             participating in the trial, or that may increase the risk associated with the study&#xD;
             participation, or that may interfere with the interpretation of the study results&#xD;
&#xD;
          -  Prior history of malignancy other than inclusion diagnosis within three years prior to&#xD;
             first dose of the study drug&#xD;
&#xD;
          -  Prior treatment with cumulative lifetime dose of anthracycline&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Sarah Cannon Research Institute - TN Oncology</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37203</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The University of Texas MD Anderson Cancer Center</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>NEXT Oncology</name>
      <address>
        <city>San Antonio</city>
        <state>Texas</state>
        <zip>78229</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>July 2023</verification_date>
  <study_first_submitted>June 18, 2020</study_first_submitted>
  <study_first_submitted_qc>June 18, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 22, 2020</study_first_posted>
  <last_update_submitted>September 4, 2023</last_update_submitted>
  <last_update_submitted_qc>September 4, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">September 7, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>ROR1</keyword>
  <keyword>Antibody-drug Conjugate</keyword>
  <keyword>Carcinoma</keyword>
  <keyword>Cancer</keyword>
  <keyword>Solid Tumor</keyword>
  <keyword>Sarcoma</keyword>
  <keyword>Triple Negative Breast Cancer</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Triple Negative Breast 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/NCT04441099
org study id: NBE-002-01
nct id: NCT04441099
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
This first-in-human study will evaluate the recommended dose for further clinical
      development, safety, tolerability, anti-tumor activity, immunogenicity, pharmacokinetics and
      pharmacodynamics of NBE-002, a novel anti-ROR1 antibody-drug conjugate, in patients with
      advanced solid tumors.
allocation: Non-Randomized
intervention model: Sequential Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Recommended Phase 2 Dose (RP2D) (Phase 1)
time frame: Up to 48 months
description: The RP2D will be determined using dose limiting toxicities (DLTs) and all other available study data
measure: Anti-tumor Activity (Phase 2)
time frame: Up to 60 months
description: Anti-tumor activity will be assessed by Response Evaluation Criteria in Solid Tumours (RECIST) v1.1
measure: Incidence of Adverse Events (Safety and Tolerability)
time frame: Up to 60 months
description: Safety and tolerability profile will be assessed by Common Terminology Criteria for Adverse Events v5.0 and summarized by type, frequency, and severity of adverse events
measure: Preliminary Anti-tumor Activity (Phase 1)
time frame: Up to 48 months
description: Preliminary anti-tumor activity will be assessed by Response Evaluation Criteria in Solid Tumours (RECIST) v1.1
measure: Concentrations of NBE-002
time frame: Up to 60 months
description: Pharmacokinetic profile will be characterized by concentrations of NBE-002
measure: Concentrations of NBE-002-reactive antibodies
time frame: Up to 60 months
description: Immunogenicity profile will be characterized by concentrations of NBE-002-reactive antibodies
arm group label: Dose-escalation Cohort (DEC)
arm group type: Experimental
description: Escalating doses of NBE-002 depending on cohort at enrollment.
arm group label: Safety-expansion Cohort (SEC)
arm group type: Experimental
description: Dose to be determined based on DEC.
arm group label: Expansion Cohort 1 (EC1)
arm group type: Experimental
description: Dose to be determined based on DEC and SEC.
arm group label: Expansion Cohort 2 (EC2)
arm group type: Experimental
description: Dose to be determined based on DEC and SEC.
intervention type: Drug
intervention name: NBE-002
description: NBE-002 will be given intravenously on Day 1 of repeated 28-day cycles.
arm group label: Dose-escalation Cohort (DEC)
arm group label: Expansion Cohort 1 (EC1)
arm group label: Expansion Cohort 2 (EC2)
arm group label: Safety-expansion Cohort (SEC)
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Triple Negative Breast Neoplasms
sharing ipd: No