xml: <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/NCT06018129</url>
    </required_header>
    <id_info>
      <org_study_id>GCT3017-01</org_study_id>
      <secondary_id>2023-503348-15-00</secondary_id>
      <nct_id>NCT06018129</nct_id>
    </id_info>
    <brief_title>A First-in-human Trial of GEN3017 in Hodgkin Lymphoma and Non-Hodgkin Lymphoma</brief_title>
    <official_title>A Phase 1/2a, Open-Label, Dose Escalation Trial of GEN3017 With Expansion Cohorts in Relapsed or Refractory CD30+ Classical Hodgkin Lymphoma and CD30+ Non-Hodgkin Lymphoma</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Genmab</agency>
        <agency_class>Industry</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Genmab</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>
      <is_us_export>Yes</is_us_export>
    </oversight_info>
    <brief_summary>
      <textblock>
        The purpose of this trial is to evaluate the safety, tolerability, immunogenicity,&#xD;
        pharmacokinetics (PK), pharmacodynamics (PD), and anti-tumor activity of GEN3017 as a&#xD;
        monotherapy in participants with relapsed or refractory (R/R) CD30-expressing lymphomas.&#xD;
  &#xD;
        GEN3017 will be administered via subcutaneous injections.&#xD;
  &#xD;
        All participants will receive active drug; no one will be given placebo.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        This multicenter trial will be conducted in 2 parts: Dose Escalation (phase 1) and Expansion&#xD;
        (phase 2a).&#xD;
  &#xD;
        The Dose Escalation Part (phase 1) of the trial will evaluate dose-limiting toxicities (DLTs)&#xD;
        to determine the recommended phase 2 dose (RP2D), and if reached, the maximum tolerated dose&#xD;
        (MTD) for R/R CD30+ classical Hodgkin lymphoma (cHL) and R/R CD30+ T-cell lymphoma (TCL),&#xD;
        respectively.&#xD;
  &#xD;
        The Expansion Part (phase 2a) will evaluate the anti-tumor activity of GEN3017 at the RP2D&#xD;
        and selected dosage(s) will be assessed together with safety, immunogenicity,&#xD;
        pharmacokinetics, and pharmacodynamics in R/R CD30+ cHL participants (including adults; and&#xD;
        adolescent and young adults) and in participants with selected R/R CD30+ TCL subtypes (adults&#xD;
        only).&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">September 29, 2023</start_date>
    <completion_date type="Anticipated">June 30, 2028</completion_date>
    <primary_completion_date type="Anticipated">December 31, 2027</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>Dose Escalation Part: Number of Participants with Dose Limiting Toxicities (DLTs)</measure>
      <time_frame>During the first cycle (Cycle length = 21 days)</time_frame>
      <description>All AEs including DLTs will be graded for severity according to the National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE), version (v) 5.0 unless otherwise specified. Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) will be evaluated according to the American society for transplantation and cellular therapy (ASTCT) criteria. Clinical tumor lysis syndrome (CTLS) will be evaluated according to the Cairo-Bishop classification.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Dose Escalation Part: Number of Participants with Adverse Events (AEs)</measure>
      <time_frame>From baseline up to 30 days after last dose of study drug or until study completion or participant withdrawal (up to 5 years)</time_frame>
    </primary_outcome>
    <primary_outcome>
      <measure>Expansion Part: Objective Response Rate (ORR)</measure>
      <time_frame>Up to 5 years</time_frame>
      <description>The ORR is defined as the percentage of participants with a best overall response (BOR) of complete response (CR) or partial response (PR) per Lugano criteria assessed by an independent review committee (IRC).</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Dose Escalation and Expansion Part: Maximum (Peak) Plasma Concentration (Cmax) of GEN3017</measure>
      <time_frame>Predose and postdose at multiple timepoints at end of each cycle up to end of treatment (Cycle length =21 days)</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Dose Escalation and Expansion Part: Time to Reach Cmax (Tmax) of GEN3017</measure>
      <time_frame>Predose and postdose at multiple timepoints at end of each cycle up to end of treatment (Cycle length = 21 days)</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Dose Escalation and Expansion Part: Pre-dose (Trough) concentration (Ctrough) of GEN3017</measure>
      <time_frame>Predose and postdose at multiple timepoints at end of each cycle up to end of treatment (Cycle length = 21 days)</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Dose Escalation and Expansion Part: Area Under the Concentration-time Curve (AUC) From Time Zero to Infinity (AUCinf) of GEN3017</measure>
      <time_frame>Predose and postdose at multiple timepoints at end of each cycle up to end of treatment (Cycle length = 21 days)</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Dose Escalation and Expansion Part: Area Under the Concentration-time Curve (AUC) From Time Zero to Last Quantifiable Sample (AUClast) of GEN3017</measure>
      <time_frame>Predose and postdose at multiple timepoints at end of each cycle up to end of treatment (Cycle length = 21 days)</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Dose Escalation and Expansion Part: Elimination Half-life (T1/2) of GEN3017</measure>
      <time_frame>Predose and postdose at multiple timepoints at end of each cycle up to end of treatment (Cycle length = 21 days)</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Dose Escalation and Expansion Part: Total Body Clearance (CL) of Drug From Plasma of GEN3017</measure>
      <time_frame>Predose and postdose at multiple timepoints at end of each cycle up to end of treatment (Cycle length = 21 days)</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Dose Escalation and Expansion Part: Volume of distribution (Vd) of GEN3017</measure>
      <time_frame>Predose and postdose at multiple timepoints at end of each cycle up to end of treatment (Cycle length = 21 days)</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Dose Escalation and Expansion Part: Number of Participants with Anti-drug Antibodies (ADA) to GEN3017</measure>
      <time_frame>Predose at multiple timepoints of each cycle up to end of treatment (Cycle length = 21 days)</time_frame>
      <description>Serum samples will be screened for ADAs binding to GEN3017 and the titer of confirmed positive samples will be reported.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Dose Escalation and Expansion Part: Objective Response Rate (ORR)</measure>
      <time_frame>Up to 5 years</time_frame>
      <description>The ORR is defined as the percentage of participants with a BOR of CR or PR per Lugano criteria based on investigator assessment.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Dose Escalation and Expansion Part: Duration of Response (DOR)</measure>
      <time_frame>Up to 5 years</time_frame>
      <description>DOR is defined as the time from the first documentation of response (CR or PR) to the date of progressive disease or death, whichever occurs earlier per Lugano criteria based on investigator and IRC assessment (expansion only).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Dose Escalation and Expansion Part: Time to Response (TTR)</measure>
      <time_frame>Up to 5 years</time_frame>
      <description>TTR is defined as the time from Cycle 1 Day 1 to first documentation of objective response in participants achieving PR or CR per Lugano criteria based on investigator and IRC assessment (expansion only).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Expansion Part: Complete Response Rate (CRR)</measure>
      <time_frame>Up to 5 years</time_frame>
      <description>CRR is defined as the number of participants with CR per Lugano criteria based on investigator and IRC assessment.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Expansion Part: Progression Free Survival (PFS)</measure>
      <time_frame>Up to 5 years</time_frame>
      <description>PFS is defined as the time from Cycle 1 Day 1 to first documented progressive disease or death due to any cause, whichever occurs earlier per Lugano criteria based on investigator and IRC assessment.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Expansion Part: Overall Survival (OS)</measure>
      <time_frame>Up to 5 years</time_frame>
      <description>OS is defined as the time from Cycle 1 Day 1 to the date of death due to any cause.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Expansion Part: Number of Participants with AEs and Serious Adverse Events (SAEs)</measure>
      <time_frame>From first dose until the end of the safety follow-up period (30 days after last dose) up to 5 years</time_frame>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">240</enrollment>
    <condition>Classical Hodgkin Lymphoma</condition>
    <condition>Non-Hodgkin Lymphoma</condition>
    <arm_group>
      <arm_group_label>R/R CD30+ cHL Cohort</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
    </arm_group>
    <arm_group>
      <arm_group_label>R/R CD30+ TCL Cohort</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
    </arm_group>
    <intervention>
      <intervention_type>Biological</intervention_type>
      <intervention_name>GEN3017</intervention_name>
      <description>Subcutaneous injection</description>
      <arm_group_label>R/R CD30+ TCL Cohort</arm_group_label>
      <arm_group_label>R/R CD30+ cHL Cohort</arm_group_label>
      <other_name>DuoBody® CD3xCD30</other_name>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Key Inclusion Criteria:&#xD;
  &#xD;
          Dose Escalation Part:&#xD;
  &#xD;
            1. Must be at least 18 years of age. For participants in the R/R cHL Cohort in the United&#xD;
               States (US) and Australia, must be at least 16 years of age.&#xD;
  &#xD;
            2. Histologically confirmed R/R cHL or R/R TCL.&#xD;
  &#xD;
            3. Participants must have at least 1 measurable lesion by fluorodeoxyglucose-positron&#xD;
               emission tomography (FDG-PET) scan demonstrating positive lesion compatible with&#xD;
               computed tomography (CT)- or magnetic resonance imaging (MRI)-defined anatomical tumor&#xD;
               sites and a CT scan (or MRI) with involvement of ≥1 measurable nodal lesion and/or ≥1&#xD;
               measurable extranodal lesion.&#xD;
  &#xD;
            4. Eastern Cooperative Oncology Group (ECOG) performance status score 0 or 1 for&#xD;
               participants 18 years of age and above. For participants ≥16 and &lt;18 years of age (US&#xD;
               and Australia only), Karnofsky score of &gt;60% per Karnofsky performance scale.&#xD;
  &#xD;
            5. Confirmed CD30-positivity in tumor biopsy prior to the first dose of GEN3017.&#xD;
  &#xD;
            6. R/R cHL Cohort:&#xD;
  &#xD;
                 -  Must have relapsed or progressive cHL after receiving at least 2 or 3 prior lines&#xD;
                    of therapy; OR&#xD;
  &#xD;
                 -  Refractory to the second line of therapy.&#xD;
  &#xD;
          Key Exclusion Criteria:&#xD;
  &#xD;
            1. Primary central nervous system (CNS) tumor or known CNS involvement.&#xD;
  &#xD;
            2. Received prior investigational CD30-targeting therapy.&#xD;
  &#xD;
            3. Autologous hematopoietic stem cell transplant (HSCT) within 60 days prior to the first&#xD;
               dose of GEN3017 or any prior allogeneic HSCT.&#xD;
  &#xD;
            4. Chemotherapy within 2 weeks or major surgery within 4 weeks prior to the first dose of&#xD;
               GEN3017.&#xD;
  &#xD;
            5. Curative radiotherapy within 4 weeks or palliative radiotherapy within 2 weeks prior&#xD;
               to the first dose of GEN3017.&#xD;
  &#xD;
            6. Treatment with an investigational drug within 4 weeks or 5 half-lives of the drug,&#xD;
               whichever is shorter prior to the first dose of GEN3017 or currently receiving any&#xD;
               other investigational agents.&#xD;
  &#xD;
            7. Prior treatment with live, attenuated vaccines within 30 days prior to the first dose&#xD;
               of GEN3017.&#xD;
  &#xD;
            8. Receiving immunosuppressive drugs or systemic corticosteroids such as prednisone at&#xD;
               doses &gt;25 milligrams (mg) daily or its equivalent within 14 days prior to the first&#xD;
               dose of GEN3017.&#xD;
  &#xD;
          NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>16 Years</minimum_age>
      <maximum_age>N/A</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Study Official</last_name>
      <role>Study Director</role>
      <affiliation>Genmab</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Genmab Trial Information</last_name>
      <phone>+4570202728</phone>
      <email>clinicaltrials@genmab.com</email>
    </overall_contact>
    <verification_date>September 2023</verification_date>
    <study_first_submitted>August 25, 2023</study_first_submitted>
    <study_first_submitted_qc>August 25, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 30, 2023</study_first_posted>
    <last_update_submitted>September 12, 2023</last_update_submitted>
    <last_update_submitted_qc>September 12, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 13, 2023</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>Lymphoma</mesh_term>
      <mesh_term>Lymphoma, Non-Hodgkin</mesh_term>
      <mesh_term>Hodgkin Disease</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT06018129
  org study id: GCT3017-01
  secondary id: 2023-503348-15-00
  nct id: NCT06018129
  lead sponsor: 
  has dmc: Yes
  is fda regulated drug: Yes
  is fda regulated device: No
  is us export: Yes
  The purpose of this trial is to evaluate the safety, tolerability, immunogenicity,
        pharmacokinetics (PK), pharmacodynamics (PD), and anti-tumor activity of GEN3017 as a
        monotherapy in participants with relapsed or refractory (R/R) CD30-expressing lymphomas.
  
        GEN3017 will be administered via subcutaneous injections.
  
        All participants will receive active drug; no one will be given placebo.
  This multicenter trial will be conducted in 2 parts: Dose Escalation (phase 1) and Expansion
        (phase 2a).
  
        The Dose Escalation Part (phase 1) of the trial will evaluate dose-limiting toxicities (DLTs)
        to determine the recommended phase 2 dose (RP2D), and if reached, the maximum tolerated dose
        (MTD) for R/R CD30+ classical Hodgkin lymphoma (cHL) and R/R CD30+ T-cell lymphoma (TCL),
        respectively.
  
        The Expansion Part (phase 2a) will evaluate the anti-tumor activity of GEN3017 at the RP2D
        and selected dosage(s) will be assessed together with safety, immunogenicity,
        pharmacokinetics, and pharmacodynamics in R/R CD30+ cHL participants (including adults; and
        adolescent and young adults) and in participants with selected R/R CD30+ TCL subtypes (adults
        only).
  allocation: Non-Randomized
  intervention model: Sequential Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Dose Escalation Part: Number of Participants with Dose Limiting Toxicities (DLTs)
  time frame: During the first cycle (Cycle length = 21 days)
  description: All AEs including DLTs will be graded for severity according to the National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE), version (v) 5.0 unless otherwise specified. Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) will be evaluated according to the American society for transplantation and cellular therapy (ASTCT) criteria. Clinical tumor lysis syndrome (CTLS) will be evaluated according to the Cairo-Bishop classification.
  measure: Dose Escalation Part: Number of Participants with Adverse Events (AEs)
  time frame: From baseline up to 30 days after last dose of study drug or until study completion or participant withdrawal (up to 5 years)
  measure: Expansion Part: Objective Response Rate (ORR)
  time frame: Up to 5 years
  description: The ORR is defined as the percentage of participants with a best overall response (BOR) of complete response (CR) or partial response (PR) per Lugano criteria assessed by an independent review committee (IRC).
  measure: Dose Escalation and Expansion Part: Maximum (Peak) Plasma Concentration (Cmax) of GEN3017
  time frame: Predose and postdose at multiple timepoints at end of each cycle up to end of treatment (Cycle length =21 days)
  measure: Dose Escalation and Expansion Part: Time to Reach Cmax (Tmax) of GEN3017
  time frame: Predose and postdose at multiple timepoints at end of each cycle up to end of treatment (Cycle length = 21 days)
  measure: Dose Escalation and Expansion Part: Pre-dose (Trough) concentration (Ctrough) of GEN3017
  time frame: Predose and postdose at multiple timepoints at end of each cycle up to end of treatment (Cycle length = 21 days)
  measure: Dose Escalation and Expansion Part: Area Under the Concentration-time Curve (AUC) From Time Zero to Infinity (AUCinf) of GEN3017
  time frame: Predose and postdose at multiple timepoints at end of each cycle up to end of treatment (Cycle length = 21 days)
  measure: Dose Escalation and Expansion Part: Area Under the Concentration-time Curve (AUC) From Time Zero to Last Quantifiable Sample (AUClast) of GEN3017
  time frame: Predose and postdose at multiple timepoints at end of each cycle up to end of treatment (Cycle length = 21 days)
  measure: Dose Escalation and Expansion Part: Elimination Half-life (T1/2) of GEN3017
  time frame: Predose and postdose at multiple timepoints at end of each cycle up to end of treatment (Cycle length = 21 days)
  measure: Dose Escalation and Expansion Part: Total Body Clearance (CL) of Drug From Plasma of GEN3017
  time frame: Predose and postdose at multiple timepoints at end of each cycle up to end of treatment (Cycle length = 21 days)
  measure: Dose Escalation and Expansion Part: Volume of distribution (Vd) of GEN3017
  time frame: Predose and postdose at multiple timepoints at end of each cycle up to end of treatment (Cycle length = 21 days)
  measure: Dose Escalation and Expansion Part: Number of Participants with Anti-drug Antibodies (ADA) to GEN3017
  time frame: Predose at multiple timepoints of each cycle up to end of treatment (Cycle length = 21 days)
  description: Serum samples will be screened for ADAs binding to GEN3017 and the titer of confirmed positive samples will be reported.
  measure: Dose Escalation and Expansion Part: Objective Response Rate (ORR)
  time frame: Up to 5 years
  description: The ORR is defined as the percentage of participants with a BOR of CR or PR per Lugano criteria based on investigator assessment.
  measure: Dose Escalation and Expansion Part: Duration of Response (DOR)
  time frame: Up to 5 years
  description: DOR is defined as the time from the first documentation of response (CR or PR) to the date of progressive disease or death, whichever occurs earlier per Lugano criteria based on investigator and IRC assessment (expansion only).
  measure: Dose Escalation and Expansion Part: Time to Response (TTR)
  time frame: Up to 5 years
  description: TTR is defined as the time from Cycle 1 Day 1 to first documentation of objective response in participants achieving PR or CR per Lugano criteria based on investigator and IRC assessment (expansion only).
  measure: Expansion Part: Complete Response Rate (CRR)
  time frame: Up to 5 years
  description: CRR is defined as the number of participants with CR per Lugano criteria based on investigator and IRC assessment.
  measure: Expansion Part: Progression Free Survival (PFS)
  time frame: Up to 5 years
  description: PFS is defined as the time from Cycle 1 Day 1 to first documented progressive disease or death due to any cause, whichever occurs earlier per Lugano criteria based on investigator and IRC assessment.
  measure: Expansion Part: Overall Survival (OS)
  time frame: Up to 5 years
  description: OS is defined as the time from Cycle 1 Day 1 to the date of death due to any cause.
  measure: Expansion Part: Number of Participants with AEs and Serious Adverse Events (SAEs)
  time frame: From first dose until the end of the safety follow-up period (30 days after last dose) up to 5 years
  arm group label: R/R CD30+ cHL Cohort
  arm group type: Experimental
  arm group label: R/R CD30+ TCL Cohort
  arm group type: Experimental
  intervention type: Biological
  intervention name: GEN3017
  description: Subcutaneous injection
  arm group label: R/R CD30+ TCL Cohort
  arm group label: R/R CD30+ cHL Cohort
  other name: DuoBody® CD3xCD30
  criteria: 
  gender: All
  minimum age: 16 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Study Official
  role: Study Director
  affiliation: Genmab
  last name: Genmab Trial Information
  phone: +4570202728
  email: clinicaltrials@genmab.com
  responsible party type: Sponsor
  mesh term: Lymphoma
  mesh term: Lymphoma, Non-Hodgkin
  mesh term: Hodgkin Disease
  sharing ipd: No