<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/NCT02978755</url>
  </required_header>
  <id_info>
    <org_study_id>C101</org_study_id>
    <nct_id>NCT02978755</nct_id>
  </id_info>
  <brief_title>First In Human Safety, Pharmacokinetics and Anti-tumoral Activity of GM102 in Gynecological Cancers</brief_title>
  <official_title>Open, Non Controlled, Multicenter, First-in-Human Study for the Evaluation of the Safety, Pharmacokinetics and Preliminary Antitumor Activity of GM102 in Patients With Advanced Pretreated Gynecological Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>GamaMabs Pharma</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>GamaMabs Pharma</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      First in Human study, assessing the safety profile, the pharmacokinetics and preliminary&#xD;
      antitumor activity of GM102, a new compound (a monoclonal antibody), in patients with&#xD;
      previously treated gynecological cancers bearing the AMHRII (anti-mullerian Hormone Receptor&#xD;
      II) receptor. The primary objective of the study is to determine the GM102 recommended dose.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      AMHRII, an embryonic receptor, is reexpressed in a subset of gynecological cancers. GM102 is&#xD;
      a humanized low fucose monoclonal antibody with a high affinity to AMHRII receptor. GM102&#xD;
      acts through enhanced capability to engage immune effector cells (macrophages, natural killer&#xD;
      (NK) cells) to trigger ADCC (antibody dependent cellular cytotoxicity) and phagocytosis of&#xD;
      tumor cells.&#xD;
&#xD;
      Patients with gynecological tumors expressing AMHRII receptor on the tumor cells in archived&#xD;
      tissue as determined prior to study entry will be eligible for C101 study.&#xD;
&#xD;
      C101 consists in a phase I part (dose and schedule escalation) and a phase Ib part&#xD;
      (expansion).&#xD;
&#xD;
      The phase I part is designed to determine the recommended phase 2 dose (RP2D) using the&#xD;
      classical 3+3 dose-finding design. In six successive escalating dose cohorts, patients will&#xD;
      receive GM102 infusions every 2 weeks until progression or toxicity. In 4 additional cohorts,&#xD;
      patients will receive GM102 infusions weekly until progression or toxicity and GM102&#xD;
      infusions combined with chemotherapy until progression or toxicity.&#xD;
&#xD;
      A Trial Steering Committee (TSC) will analyze and qualify the toxicities and will provide&#xD;
      recommendations according to the dose administration rules defined in the protocol.&#xD;
&#xD;
      At the end of the phase I part, the RP2D will be determined, taking into account dose&#xD;
      limiting toxicities (DLTs), overall toxicity, pharmacokinetics and pharmacodynamic effects of&#xD;
      GM102.&#xD;
&#xD;
      The Phase Ib part of the study will confirm the tolerance of the selected dose (RP2D) and&#xD;
      will assess antitumoral activity of GM102 in three parallel cohorts of patients with Sex&#xD;
      Cord-Stromal tumors, and AMHRII positive ovarian and cervix cancers. Patients will be treated&#xD;
      until progression or toxicity.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>June 2016</start_date>
  <completion_date type="Actual">June 10, 2020</completion_date>
  <primary_completion_date type="Actual">June 10, 2020</primary_completion_date>
  <phase>Phase 1</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>
    <intervention_model_description>phase 1 escalation GM102 single agent&#xD;
phase 1 escalation GM102 combined with paclitaxel and carboplatin&#xD;
phase 1b: 3 parallel expansion cohorts at the recommended dose of GM102 single agent</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Phase I part: incidence of Dose Limiting Toxicities (DLTs)</measure>
    <time_frame>Four weeks</time_frame>
    <description>Number of patients in the DLT evaluable population experiencing at least one DLT</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Phase Ib part: incidence of Serious Adverse Events (SAEs) and Treatment-Emergent Adverse Events (TEAEs) at Recommended Phase 2 Dose (RP2D)</measure>
    <time_frame>Through study completion, an average of 1 year</time_frame>
    <description>Number of patients with at least one AE</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>PK: Maximum Serum Concentration [Cmax]</measure>
    <time_frame>up to 16 weeks</time_frame>
    <description>Cycle 1 Day 1 pre-dose, Cycle 1 Day 1 End Of Infusion (EOI), Cycle 1 Day 1 EOI + 3 hours, Cycle 1 Day 2, Cycle 1 Day 3, Cycle 1 Day 8, Cycle 1 Day 15 pre-dose, Cycle 1 Day 15 EOI, Cycle 2 Day 1 pre-dose, Cycle 2 Day 1 EOI, Cycle 2 Day 15 pre-dose, Cycle 2 Day 15 EOI, Cycle 3 Day 1 pre-dose, Cycle 3 Day 1 EOI, Cycle 3 Day 15 pre-dose, Cycle 3 Day 15 EOI, Cycle 4 Day 1 pre-dose, Cycle 4 Day 1 EOI, Cycle 4 Day 15 pre-dose, Cycle 4 Day 15 EOI</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PK: Area Under the Curve [AUC]</measure>
    <time_frame>up to 16 weeks</time_frame>
    <description>Cycle 1 Day 1 pre-dose, Cycle 1 Day 1 End Of Infusion (EOI), Cycle 1 Day 1 EOI + 3 hours, Cycle 1 Day 2, Cycle 1 Day 3, Cycle 1 Day 8, Cycle 1 Day 15 pre-dose, Cycle 1 Day 15 EOI, Cycle 2 Day 1 pre-dose, Cycle 2 Day 1 EOI, Cycle 2 Day 15 pre-dose, Cycle 2 Day 15 EOI, Cycle 3 Day 1 pre-dose, Cycle 3 Day 1 EOI, Cycle 3 Day 15 pre-dose, Cycle 3 Day 15 EOI, Cycle 4 Day 1 pre-dose, Cycle 4 Day 1 EOI, Cycle 4 Day 15 pre-dose, Cycle 4 Day 15 EOI</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Response Rate using Response Evaluation Criteria In Solid Tumors (RECIST) 1.1</measure>
    <time_frame>Through study completion</time_frame>
    <description>Percentage of patients who achieved a Complete Response (CR) or a Partial Response (PR) based on RECIST version 1.1</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clinical benefit rate</measure>
    <time_frame>up to 3 months</time_frame>
    <description>Percentage of patients achieving Complete Response (CR), Partial Response (PR) or Stable Disease (SD) superior to 3 months</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of response</measure>
    <time_frame>Through study completion</time_frame>
    <description>Duration of overall response in months for patients who achieved PR and/or CR</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to progression (TTP)</measure>
    <time_frame>Through study completion</time_frame>
    <description>Time from first dose received until objective tumor progression</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">78</enrollment>
  <condition>Neoplasm, Gynecologic</condition>
  <arm_group>
    <arm_group_label>GM102 escalating doses</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>8 successive cohorts</description>
  </arm_group>
  <arm_group>
    <arm_group_label>GM102 escalating doses + carboplatin+paclitaxel</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>2 successive cohorts</description>
  </arm_group>
  <arm_group>
    <arm_group_label>GM102 recommended dose</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>3 parallel cohorts in sex cord stromal, epithelial ovarian and cervix cancers</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>GM102</intervention_name>
    <description>GM102 escalating doses (phase1)</description>
    <arm_group_label>GM102 escalating doses</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>GM102 escalating doses</intervention_name>
    <description>GM102 escalating doses combined with paclitaxel and carboplatin</description>
    <arm_group_label>GM102 escalating doses + carboplatin+paclitaxel</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>GM102</intervention_name>
    <description>GM102 single agent at recommended dose in 3 parallel cohorts (sex cord, epithelial ovarian, cervix cancers)</description>
    <arm_group_label>GM102 recommended dose</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Locally advanced, or metastatic recurrent gynecological cancer, for whom no standard&#xD;
             alternative therapy is available, having received at least one line of therapy and&#xD;
             expressing AMHRII on tumor cells.&#xD;
&#xD;
          -  If possible at least one lesion should be identified for 2 biopsies: a baseline biopsy&#xD;
             and an under-treatment biopsy for AMHRII expression and GM102 pharmacodynamics&#xD;
             evaluation.&#xD;
&#xD;
          -  Available tumor block or at least 10 slides from formalin-fixed paraffin-embedded&#xD;
             (FFPE) archival tissue.&#xD;
&#xD;
          -  At least one measurable lesion by RECIST (Response Evaluation Criteria in Solid&#xD;
             Tumors) on screening CT-scan.&#xD;
&#xD;
          -  Written Informed Consent forms.&#xD;
&#xD;
          -  Willing and able to comply with the trial requirements.&#xD;
&#xD;
          -  Covered by healthcare insurance in accordance with local requirements.&#xD;
&#xD;
        For phase 1b, only patients with either Sex cord stromal tumors or epithelial ovarian&#xD;
        cancer or cervix cancer will be eligible&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Age &lt; 18 years old.&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status &gt; 1&#xD;
&#xD;
          -  Life expectancy &lt; 12 weeks.&#xD;
&#xD;
          -  Known or symptomatic brain metastasis (other than totally resected or previously&#xD;
             irradiated and non-progressive/relapsing) or lepto-meningeal carcinomatosis.&#xD;
&#xD;
          -  Concurrent treatment with any other anticancer therapy.&#xD;
&#xD;
          -  Concurrent chronic corticosteroid treatment.&#xD;
&#xD;
          -  Known severe anaphylactic or other hypersensitivity reactions secondary to a prior&#xD;
             exposure to human antibodies or to any protein product.&#xD;
&#xD;
          -  Washout period before treatment initiation: &lt; 3 weeks or 5 times the half-life,&#xD;
             whichever is shorter, for prior antitumor therapy (small molecules and/or&#xD;
             antibody-drug conjugates, radiotherapy) or 6 weeks for monoclonal antibodies.&#xD;
&#xD;
          -  Any active concomitant malignancy.&#xD;
&#xD;
          -  Serious concomitant illness e.g. active infection requiring systemic antibiotic,&#xD;
             antifungal or antiviral drug, or physical examination or laboratory abnormalities,&#xD;
             that, in the opinion of the Investigator, would compromise protocol objectives.&#xD;
&#xD;
          -  Poor bone marrow reserve as defined by neutrophils &lt; 1.0 x 10E9/L or haemoglobin &lt; 9.0&#xD;
             g/dL or platelet count &lt; 100 x 10E9/L.&#xD;
&#xD;
          -  Poor organ function as defined by any one of the following: left ventricular ejection&#xD;
             fraction ≤ 40%, serum creatinine &gt; 1.5 x upper limit of normal (ULN), total bilirubin&#xD;
             &gt; 1.5 x ULN, AST and ALT&gt; 2.5 x ULN in the absence of liver metastasis or &gt; 5 x ULN in&#xD;
             case of documented liver metastasis.&#xD;
&#xD;
          -  Non-resolution of any prior treatment related toxicity to &lt; Grade 2, except for&#xD;
             alopecia according to National Cancer Institute-Common Terminology Criteria for&#xD;
             Adverse Events (NCI-CTCAE) v4.03.&#xD;
&#xD;
          -  Pregnancy or breastfeeding.&#xD;
&#xD;
          -  Patient with reproductive potential who do not agree to use an accepted effective&#xD;
             method of contraception - investigator's judgment - during the study period and for at&#xD;
             least 4 months following completion of study treatment.&#xD;
&#xD;
          -  Patient participating in another clinical trial investigating a treatment during the&#xD;
             study and within 30 days prior to first study treatment administration.&#xD;
&#xD;
          -  Patient deprived of her liberty by a judicial or administrative decision, patient&#xD;
             admitted to a hospital, social institution or who is under a measure of legal&#xD;
             protection, patient hospitalized without consent or who is in an emergency situation.&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Alexandra Leary, MD/PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Gustave Roussy center, Villejuif, France</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Institut Bordet</name>
      <address>
        <city>Brussels</city>
        <zip>1000</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UZ Leuven</name>
      <address>
        <city>Leuven</city>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU Besançon</name>
      <address>
        <city>Besançon</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Institut Bergonié</name>
      <address>
        <city>Bordeaux</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre Oscar Lambret</name>
      <address>
        <city>Lille</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre Leon Berard</name>
      <address>
        <city>Lyon</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Institut de cancerologie de Montpellier</name>
      <address>
        <city>Montpellier</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Institut de cancerologie de Lorraine</name>
      <address>
        <city>Nancy</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Institut Curie</name>
      <address>
        <city>Paris</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Institut Universitaire Cancer Toulouse - Oncopole</name>
      <address>
        <city>Toulouse</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Gustave Roussy</name>
      <address>
        <city>Villejuif</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Royal Marsden Hospital</name>
      <address>
        <city>London</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Belgium</country>
    <country>France</country>
    <country>United Kingdom</country>
  </location_countries>
  <verification_date>March 2022</verification_date>
  <study_first_submitted>November 23, 2016</study_first_submitted>
  <study_first_submitted_qc>November 30, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 1, 2016</study_first_posted>
  <last_update_submitted>March 27, 2022</last_update_submitted>
  <last_update_submitted_qc>March 27, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">April 6, 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>Genital Neoplasms, Female</mesh_term>
  </condition_browse>
  <!-- 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/NCT02978755
org study id: C101
nct id: NCT02978755
lead sponsor: 
has dmc: No
First in Human study, assessing the safety profile, the pharmacokinetics and preliminary
      antitumor activity of GM102, a new compound (a monoclonal antibody), in patients with
      previously treated gynecological cancers bearing the AMHRII (anti-mullerian Hormone Receptor
      II) receptor. The primary objective of the study is to determine the GM102 recommended dose.
AMHRII, an embryonic receptor, is reexpressed in a subset of gynecological cancers. GM102 is
      a humanized low fucose monoclonal antibody with a high affinity to AMHRII receptor. GM102
      acts through enhanced capability to engage immune effector cells (macrophages, natural killer
      (NK) cells) to trigger ADCC (antibody dependent cellular cytotoxicity) and phagocytosis of
      tumor cells.

      Patients with gynecological tumors expressing AMHRII receptor on the tumor cells in archived
      tissue as determined prior to study entry will be eligible for C101 study.

      C101 consists in a phase I part (dose and schedule escalation) and a phase Ib part
      (expansion).

      The phase I part is designed to determine the recommended phase 2 dose (RP2D) using the
      classical 3+3 dose-finding design. In six successive escalating dose cohorts, patients will
      receive GM102 infusions every 2 weeks until progression or toxicity. In 4 additional cohorts,
      patients will receive GM102 infusions weekly until progression or toxicity and GM102
      infusions combined with chemotherapy until progression or toxicity.

      A Trial Steering Committee (TSC) will analyze and qualify the toxicities and will provide
      recommendations according to the dose administration rules defined in the protocol.

      At the end of the phase I part, the RP2D will be determined, taking into account dose
      limiting toxicities (DLTs), overall toxicity, pharmacokinetics and pharmacodynamic effects of
      GM102.

      The Phase Ib part of the study will confirm the tolerance of the selected dose (RP2D) and
      will assess antitumoral activity of GM102 in three parallel cohorts of patients with Sex
      Cord-Stromal tumors, and AMHRII positive ovarian and cervix cancers. Patients will be treated
      until progression or toxicity.
allocation: Non-Randomized
intervention model: Sequential Assignment
intervention model description: phase 1 escalation GM102 single agent
phase 1 escalation GM102 combined with paclitaxel and carboplatin
phase 1b: 3 parallel expansion cohorts at the recommended dose of GM102 single agent
primary purpose: Treatment
masking: None (Open Label)
measure: Phase I part: incidence of Dose Limiting Toxicities (DLTs)
time frame: Four weeks
description: Number of patients in the DLT evaluable population experiencing at least one DLT
measure: Phase Ib part: incidence of Serious Adverse Events (SAEs) and Treatment-Emergent Adverse Events (TEAEs) at Recommended Phase 2 Dose (RP2D)
time frame: Through study completion, an average of 1 year
description: Number of patients with at least one AE
measure: PK: Maximum Serum Concentration [Cmax]
time frame: up to 16 weeks
description: Cycle 1 Day 1 pre-dose, Cycle 1 Day 1 End Of Infusion (EOI), Cycle 1 Day 1 EOI + 3 hours, Cycle 1 Day 2, Cycle 1 Day 3, Cycle 1 Day 8, Cycle 1 Day 15 pre-dose, Cycle 1 Day 15 EOI, Cycle 2 Day 1 pre-dose, Cycle 2 Day 1 EOI, Cycle 2 Day 15 pre-dose, Cycle 2 Day 15 EOI, Cycle 3 Day 1 pre-dose, Cycle 3 Day 1 EOI, Cycle 3 Day 15 pre-dose, Cycle 3 Day 15 EOI, Cycle 4 Day 1 pre-dose, Cycle 4 Day 1 EOI, Cycle 4 Day 15 pre-dose, Cycle 4 Day 15 EOI
measure: PK: Area Under the Curve [AUC]
time frame: up to 16 weeks
description: Cycle 1 Day 1 pre-dose, Cycle 1 Day 1 End Of Infusion (EOI), Cycle 1 Day 1 EOI + 3 hours, Cycle 1 Day 2, Cycle 1 Day 3, Cycle 1 Day 8, Cycle 1 Day 15 pre-dose, Cycle 1 Day 15 EOI, Cycle 2 Day 1 pre-dose, Cycle 2 Day 1 EOI, Cycle 2 Day 15 pre-dose, Cycle 2 Day 15 EOI, Cycle 3 Day 1 pre-dose, Cycle 3 Day 1 EOI, Cycle 3 Day 15 pre-dose, Cycle 3 Day 15 EOI, Cycle 4 Day 1 pre-dose, Cycle 4 Day 1 EOI, Cycle 4 Day 15 pre-dose, Cycle 4 Day 15 EOI
measure: Response Rate using Response Evaluation Criteria In Solid Tumors (RECIST) 1.1
time frame: Through study completion
description: Percentage of patients who achieved a Complete Response (CR) or a Partial Response (PR) based on RECIST version 1.1
measure: Clinical benefit rate
time frame: up to 3 months
description: Percentage of patients achieving Complete Response (CR), Partial Response (PR) or Stable Disease (SD) superior to 3 months
measure: Duration of response
time frame: Through study completion
description: Duration of overall response in months for patients who achieved PR and/or CR
measure: Time to progression (TTP)
time frame: Through study completion
description: Time from first dose received until objective tumor progression
arm group label: GM102 escalating doses
arm group type: Experimental
description: 8 successive cohorts
arm group label: GM102 escalating doses + carboplatin+paclitaxel
arm group type: Experimental
description: 2 successive cohorts
arm group label: GM102 recommended dose
arm group type: Experimental
description: 3 parallel cohorts in sex cord stromal, epithelial ovarian and cervix cancers
intervention type: Drug
intervention name: GM102
description: GM102 escalating doses (phase1)
arm group label: GM102 escalating doses
intervention type: Drug
intervention name: GM102 escalating doses
description: GM102 escalating doses combined with paclitaxel and carboplatin
arm group label: GM102 escalating doses + carboplatin+paclitaxel
intervention type: Drug
intervention name: GM102
description: GM102 single agent at recommended dose in 3 parallel cohorts (sex cord, epithelial ovarian, cervix cancers)
arm group label: GM102 recommended dose
criteria: 
gender: Female
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Alexandra Leary, MD/PhD
role: Principal Investigator
affiliation: Gustave Roussy center, Villejuif, France
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Belgium
country: France
country: United Kingdom
responsible party type: Sponsor
mesh term: Genital Neoplasms, Female