<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/NCT03769181</url>
  </required_header>
  <id_info>
    <org_study_id>ACT15320</org_study_id>
    <secondary_id>2018-002442-37</secondary_id>
    <secondary_id>U1111-1211-9010</secondary_id>
    <nct_id>NCT03769181</nct_id>
  </id_info>
  <brief_title>A Study of Isatuximab-based Therapy in Participants With Lymphoma</brief_title>
  <official_title>A Phase 1/2 Open-label, Multi-center, Safety, Preliminary Efficacy and Pharmacokinetic (PK) Study of Isatuximab in Combination With Other Anti-cancer Therapies in Participants With Lymphoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Sanofi</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Sanofi</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>
      Primary Objectives:&#xD;
&#xD;
      Phase 1&#xD;
&#xD;
      -To characterize the safety and tolerability of isatuximab in combination with cemiplimab in&#xD;
      participants with relapsed and refractory classic Hodgkin's lymphoma (cHL), diffuse large&#xD;
      B-cell lymphoma (DLBCL) or peripheral T-cell lymphoma (PTCL), and to confirm the recommended&#xD;
      Phase 2 dose (RP2D).&#xD;
&#xD;
      Phase 2&#xD;
&#xD;
        -  Cohort A1 (anti-programmed cell death protein 1/ligand 1 [PD-1/PD-L1] naïve cHL): To&#xD;
           assess the complete remission (CR) rate of isatuximab in combination with cemiplimab.&#xD;
&#xD;
        -  Cohort A2 (cHL progressing from PD-1/PD-L1), B (DLBCL) and C (PTCL): To assess the&#xD;
           objective response rate (ORR) of isatuximab in combination with cemiplimab.&#xD;
&#xD;
      Secondary Objectives:&#xD;
&#xD;
        -  To evaluate the safety of the RP2D of the combination of isatuximab with cemiplimab.&#xD;
&#xD;
        -  To evaluate the safety of the combination of isatuximab with cemiplimab and radiotherapy&#xD;
           in patients with cHL.&#xD;
&#xD;
        -  To evaluate the immunogenicity of isatuximab and cemiplimab when given in combination.&#xD;
&#xD;
        -  To characterize the pharmacokinetic (PK) profile of isatuximab and cemiplimab when given&#xD;
           in combination.&#xD;
&#xD;
        -  To assess overall efficacy of isatuximab in combination with cemiplimab and isatuximab&#xD;
           in combination with cemiplimab and radiotherapy.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The total study duration per patient is up to 28 months, including an up to 28-day screening&#xD;
      period, an up to 96-week treatment period, and a 90-day safety follow up period.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Study was stopped after interim analysis for all 4 cohorts with results either not fulfilling&#xD;
    the pre-planned interim analysis criteria or fulfilling the criteria but as per sponsor&#xD;
    decision. It was not due to any safety concern&#xD;
  </why_stopped>
  <start_date type="Actual">December 11, 2018</start_date>
  <completion_date type="Actual">November 8, 2022</completion_date>
  <primary_completion_date type="Actual">November 8, 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>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Phase 1 - Dose limiting toxicities (DLTs); Recommended Phase 2 dose (RP2D)</measure>
    <time_frame>1st Cycle - 28 days</time_frame>
    <description>DLTs as observed during DLT-observation period; Dose selected for the Phase 2 portion</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Phase 2 - Cohort A1 (anti-PD-1/PD-L1 naive cHL): Complete Remission Rate</measure>
    <time_frame>Up to 24 weeks after last patient treated in a given cohort</time_frame>
    <description>The proportion of participants who have a Complete Remission as a best overall response during the isatuximab + cemiplimab therapy period using the Lugano response criteria 2014</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Phase 2 - Cohort A2 (cHL progressing from PD-1/PD-L1), B (DLBCL) and C (PTCL): Response Rate</measure>
    <time_frame>Up to 24 weeks after last patient treated in a given cohort</time_frame>
    <description>The proportion of participants who have a Complete Response or Partial Response as a best overall response during isatuximab + cemiplimab therapy period using the Lugano response criteria 2014</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Adverse Events (AEs)/Serious Adverse Events (SAEs) for isatuximab + cemiplimab</measure>
    <time_frame>Up to 90 days after last study treatment administration (Up to approximately 27 months after first study treatment administration)</time_frame>
    <description>Number of patients with AEs/SAEs</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adverse Events/Serious Adverse Events for isatuximab + cemiplimab + radiotherapy</measure>
    <time_frame>Up to 90 days after last study treatment administration (Up to approximately 27 months after first study treatment administration)</time_frame>
    <description>Number of patients with AEs/SAEs in cohorts A1 and A2</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Immunogenicity: Anti-drug antibody levels</measure>
    <time_frame>Up to 90 days following the last administration of study treatment or at the primary analysis cut-of date, whichever comes first</time_frame>
    <description>Anti-drug antibody (ADA) levels against isatuximab and against cemiplimab</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetic evaluation: Cmax</measure>
    <time_frame>Up to 90 days following the last administration of study treatment or at the primary analysis cut-of date, whichever comes first</time_frame>
    <description>Maximum concentration observed after the first infusion</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetic evaluation: Ctrough</measure>
    <time_frame>Up to 90 days following the last administration of study treatment or at the primary analysis cut-of date, whichever comes first</time_frame>
    <description>Concentrations observed just before treatment administration during repeated dosing</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetic evaluation: AUC0-T</measure>
    <time_frame>Up to 90 days following the last administration of study treatment or at the primary analysis cut-of date, whichever comes first</time_frame>
    <description>Area under the concentration versus time curve calculated using the trapezoidal method over the dosing interval (ie, 6 days for isatuximab or 21 days for cemiplimab)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Tumor burden change</measure>
    <time_frame>Up to 24 weeks after last patient treated in a given cohort</time_frame>
    <description>The best percent-change from baseline</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Disease control rate</measure>
    <time_frame>Up to 24 weeks after last patient treated in a given cohort</time_frame>
    <description>The sum of complete responses (CR) + partial responses (PR) + stable disease (SD)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of response</measure>
    <time_frame>Up to 24 weeks after last patient treated in a given cohort</time_frame>
    <description>The time from the date of the first response (PR or CR in radiographic objective response) that is subsequently confirmed to the date of first confirmed disease progression or death, whichever occurs first</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression free survival</measure>
    <time_frame>Up to 24 weeks after last patient treated in a given cohort</time_frame>
    <description>The time from the first study treatment administration to the date of first documentation of progressive disease or death, whichever comes first</description>
  </secondary_outcome>
  <number_of_arms>5</number_of_arms>
  <enrollment type="Actual">58</enrollment>
  <condition>Lymphoma</condition>
  <arm_group>
    <arm_group_label>Phase 1: cHl/DLBCL/PTCL</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Isatuximab dose 1 or 2 depending on dose limiting toxicities (DLTs) observed and cemiplimab predefined dose</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Phase 2: Cohort A1: cHL, anti PD-1/PD-L1 naïve</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Isatuximab and cemiplimab combination: Isatuximab dose determined in Phase 1 part of study and cemiplimab predefined dose</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Phase 2: Cohort A2: cHL, anti PD-1/PD-L1 progressor</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Isatuximab and cemiplimab combination: Isatuximab dose determined in Phase 1 part of study and cemiplimab predefined dose</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Phase 2: Cohort B: DLBCL, anti PD-1/PD-L1 naïve</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Isatuximab and cemiplimab combination: Isatuximab dose determined in Phase 1 part of study and cemiplimab predefined dose</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Phase 2: Cohort C: PTCL, anti PD-1/PD-L1 naïve</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Isatuximab and cemiplimab combination: Isatuximab dose determined in Phase 1 part of study and cemiplimab predefined dose</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>isatuximab SAR650984</intervention_name>
    <description>Pharmaceutical form: solution for infusion&#xD;
Route of administration: intravenous</description>
    <arm_group_label>Phase 1: cHl/DLBCL/PTCL</arm_group_label>
    <arm_group_label>Phase 2: Cohort A1: cHL, anti PD-1/PD-L1 naïve</arm_group_label>
    <arm_group_label>Phase 2: Cohort A2: cHL, anti PD-1/PD-L1 progressor</arm_group_label>
    <arm_group_label>Phase 2: Cohort B: DLBCL, anti PD-1/PD-L1 naïve</arm_group_label>
    <arm_group_label>Phase 2: Cohort C: PTCL, anti PD-1/PD-L1 naïve</arm_group_label>
    <other_name>Sarclisa</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>cemiplimab REGN2810</intervention_name>
    <description>Pharmaceutical form: solution for infusion&#xD;
Route of administration: intravenous</description>
    <arm_group_label>Phase 1: cHl/DLBCL/PTCL</arm_group_label>
    <arm_group_label>Phase 2: Cohort A1: cHL, anti PD-1/PD-L1 naïve</arm_group_label>
    <arm_group_label>Phase 2: Cohort A2: cHL, anti PD-1/PD-L1 progressor</arm_group_label>
    <arm_group_label>Phase 2: Cohort B: DLBCL, anti PD-1/PD-L1 naïve</arm_group_label>
    <arm_group_label>Phase 2: Cohort C: PTCL, anti PD-1/PD-L1 naïve</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion criteria:&#xD;
&#xD;
          -  Participants must be ≥ 12 years of age inclusive, at the time of signing the informed&#xD;
             consent&#xD;
&#xD;
          -  Disease location amenable to tumor biopsy at baseline&#xD;
&#xD;
          -  Measurable disease&#xD;
&#xD;
          -  For Cohort A1 (classic Hodgkin's lymphoma [cHL] anti-programmed cell death protein&#xD;
             1/ligand 1 [PD-1/PD-L1] inhibitor naïve): Histologically confirmed advanced cHL that&#xD;
             has relapsed or progressed after at least 3 lines of systemic therapy that may include&#xD;
             autologous hematopoietic stem cell transplant (auto-HSCT) or auto-HSCT and brentuximab&#xD;
             vedotin (BV)&#xD;
&#xD;
          -  For Cohort A2 (cHL anti-PD-1/PD-L1 inhibitor progressor): Histologically confirmed&#xD;
             advanced cHL which has relapsed or progressed after one previous anti-PD-1/PD-L1&#xD;
             containing regimen as the most recent prior therapy but no more than 4 lines of&#xD;
             previous chemotherapy including the anti-PD-1/PD-L1 containing regimen and&#xD;
             documentation of benefit during or after the anti-PD-1/PD-L1 containing regimen within&#xD;
             4 months prior to initiation of investigational medicinal product (IMP)&#xD;
&#xD;
          -  For Cohort B (diffuse large B-cell lymphoma [DLBCL]): Histologically confirmed&#xD;
             advanced DLBCL that has relapsed or progressed after 2 lines of systemic therapy&#xD;
             including auto-HSCT or 2 lines of systemic therapy for participants who are not&#xD;
             eligible for auto-HSCT&#xD;
&#xD;
          -  For Cohort C (peripheral T-cell lymphoma [PTCL]): Histologically confirmed advanced&#xD;
             PTCL that has relapsed or progressed after either first-line chemotherapy and&#xD;
             auto-HSCT as consolidation of first remission or first-line chemotherapy if&#xD;
             participants are ineligible for auto-HSCT&#xD;
&#xD;
          -  Body weight of &gt; 45 kg for patients with age &lt;18 years&#xD;
&#xD;
        Exclusion criteria:&#xD;
&#xD;
          -  Prior exposure to agent that blocks CD38&#xD;
&#xD;
          -  For patients with cHL (PD-1/PD-L1 naïve), DLBCL or PTCL prior exposure to any agent&#xD;
             (approved or investigational) that blocks the PD-1/PD-L1, PD-L2, CD137, CTLA-4 or&#xD;
             LAG-3&#xD;
&#xD;
          -  Evidence of other immune related disease/conditions&#xD;
&#xD;
          -  Has received a live-virus vaccination within 28 days of planned treatment start;&#xD;
             seasonal flu vaccines that do not contain live virus are permitted&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≥2&#xD;
&#xD;
          -  Poor bone marrow reserve&#xD;
&#xD;
          -  Poor organ function&#xD;
&#xD;
        The above information is not intended to contain all considerations relevant to a patient's&#xD;
        potential participation in a clinical trial.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>12 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Clinical Sciences &amp; Operations</last_name>
    <role>Study Director</role>
    <affiliation>Sanofi</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Investigational Site Number :2500005</name>
      <address>
        <city>Dijon</city>
        <zip>21000</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :2500004</name>
      <address>
        <city>Montpellier</city>
        <zip>34295</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :2500002</name>
      <address>
        <city>Nantes</city>
        <zip>44093</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :2500007</name>
      <address>
        <city>Pessac</city>
        <zip>33600</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :2500001</name>
      <address>
        <city>Villejuif</city>
        <zip>94800</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :3800003</name>
      <address>
        <city>Rozzano</city>
        <state>Milano</state>
        <zip>20089</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :3800002</name>
      <address>
        <city>Bologna</city>
        <zip>40138</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :3800006</name>
      <address>
        <city>Brescia</city>
        <zip>25123</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :4100001</name>
      <address>
        <city>Gangnam-gu</city>
        <state>Seoul-teukbyeolsi</state>
        <zip>06351</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :4100002</name>
      <address>
        <city>Seoul</city>
        <state>Seoul-teukbyeolsi</state>
        <zip>03080</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :5280002</name>
      <address>
        <city>Amsterdam</city>
        <zip>1081 HV</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :5280001</name>
      <address>
        <city>Maastricht</city>
        <zip>6229 HX</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :6200002</name>
      <address>
        <city>Coimbra</city>
        <zip>3000-075</zip>
        <country>Portugal</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :6200004</name>
      <address>
        <city>Lisboa</city>
        <zip>1649-035</zip>
        <country>Portugal</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :6200003</name>
      <address>
        <city>Porto</city>
        <zip>4200</zip>
        <country>Portugal</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :7240003</name>
      <address>
        <city>Barcelona</city>
        <state>Barcelona [Barcelona]</state>
        <zip>08035</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :7240005</name>
      <address>
        <city>Barcelona</city>
        <state>Barcelona [Barcelona]</state>
        <zip>08036</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :7240002</name>
      <address>
        <city>Hospitalet de Llobregat</city>
        <state>Barcelona [Barcelona]</state>
        <zip>08908</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :7240004</name>
      <address>
        <city>Madrid / Madrid</city>
        <state>Madrid, Comunidad De</state>
        <zip>28040</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :1580002</name>
      <address>
        <city>Taichung</city>
        <zip>40447</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
    <country>Italy</country>
    <country>Korea, Republic of</country>
    <country>Netherlands</country>
    <country>Portugal</country>
    <country>Spain</country>
    <country>Taiwan</country>
  </location_countries>
  <verification_date>March 2023</verification_date>
  <study_first_submitted>November 29, 2018</study_first_submitted>
  <study_first_submitted_qc>December 5, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 7, 2018</study_first_posted>
  <last_update_submitted>March 10, 2023</last_update_submitted>
  <last_update_submitted_qc>March 10, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">March 14, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Anti-CD38 monoclonal antibody</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lymphoma</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cemiplimab</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org</ipd_description>
  </patient_data>
  <pending_results>
    <submitted>August 15, 2023</submitted>
    <returned>September 12, 2023</returned>
  </pending_results>
  <!-- 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/NCT03769181
org study id: ACT15320
secondary id: 2018-002442-37
secondary id: U1111-1211-9010
nct id: NCT03769181
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
Primary Objectives:

      Phase 1

      -To characterize the safety and tolerability of isatuximab in combination with cemiplimab in
      participants with relapsed and refractory classic Hodgkin's lymphoma (cHL), diffuse large
      B-cell lymphoma (DLBCL) or peripheral T-cell lymphoma (PTCL), and to confirm the recommended
      Phase 2 dose (RP2D).

      Phase 2

        -  Cohort A1 (anti-programmed cell death protein 1/ligand 1 [PD-1/PD-L1] naïve cHL): To
           assess the complete remission (CR) rate of isatuximab in combination with cemiplimab.

        -  Cohort A2 (cHL progressing from PD-1/PD-L1), B (DLBCL) and C (PTCL): To assess the
           objective response rate (ORR) of isatuximab in combination with cemiplimab.

      Secondary Objectives:

        -  To evaluate the safety of the RP2D of the combination of isatuximab with cemiplimab.

        -  To evaluate the safety of the combination of isatuximab with cemiplimab and radiotherapy
           in patients with cHL.

        -  To evaluate the immunogenicity of isatuximab and cemiplimab when given in combination.

        -  To characterize the pharmacokinetic (PK) profile of isatuximab and cemiplimab when given
           in combination.

        -  To assess overall efficacy of isatuximab in combination with cemiplimab and isatuximab
           in combination with cemiplimab and radiotherapy.
The total study duration per patient is up to 28 months, including an up to 28-day screening
      period, an up to 96-week treatment period, and a 90-day safety follow up period.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Phase 1 - Dose limiting toxicities (DLTs); Recommended Phase 2 dose (RP2D)
time frame: 1st Cycle - 28 days
description: DLTs as observed during DLT-observation period; Dose selected for the Phase 2 portion
measure: Phase 2 - Cohort A1 (anti-PD-1/PD-L1 naive cHL): Complete Remission Rate
time frame: Up to 24 weeks after last patient treated in a given cohort
description: The proportion of participants who have a Complete Remission as a best overall response during the isatuximab + cemiplimab therapy period using the Lugano response criteria 2014
measure: Phase 2 - Cohort A2 (cHL progressing from PD-1/PD-L1), B (DLBCL) and C (PTCL): Response Rate
time frame: Up to 24 weeks after last patient treated in a given cohort
description: The proportion of participants who have a Complete Response or Partial Response as a best overall response during isatuximab + cemiplimab therapy period using the Lugano response criteria 2014
measure: Adverse Events (AEs)/Serious Adverse Events (SAEs) for isatuximab + cemiplimab
time frame: Up to 90 days after last study treatment administration (Up to approximately 27 months after first study treatment administration)
description: Number of patients with AEs/SAEs
measure: Adverse Events/Serious Adverse Events for isatuximab + cemiplimab + radiotherapy
time frame: Up to 90 days after last study treatment administration (Up to approximately 27 months after first study treatment administration)
description: Number of patients with AEs/SAEs in cohorts A1 and A2
measure: Immunogenicity: Anti-drug antibody levels
time frame: Up to 90 days following the last administration of study treatment or at the primary analysis cut-of date, whichever comes first
description: Anti-drug antibody (ADA) levels against isatuximab and against cemiplimab
measure: Pharmacokinetic evaluation: Cmax
time frame: Up to 90 days following the last administration of study treatment or at the primary analysis cut-of date, whichever comes first
description: Maximum concentration observed after the first infusion
measure: Pharmacokinetic evaluation: Ctrough
time frame: Up to 90 days following the last administration of study treatment or at the primary analysis cut-of date, whichever comes first
description: Concentrations observed just before treatment administration during repeated dosing
measure: Pharmacokinetic evaluation: AUC0-T
time frame: Up to 90 days following the last administration of study treatment or at the primary analysis cut-of date, whichever comes first
description: Area under the concentration versus time curve calculated using the trapezoidal method over the dosing interval (ie, 6 days for isatuximab or 21 days for cemiplimab)
measure: Tumor burden change
time frame: Up to 24 weeks after last patient treated in a given cohort
description: The best percent-change from baseline
measure: Disease control rate
time frame: Up to 24 weeks after last patient treated in a given cohort
description: The sum of complete responses (CR) + partial responses (PR) + stable disease (SD)
measure: Duration of response
time frame: Up to 24 weeks after last patient treated in a given cohort
description: The time from the date of the first response (PR or CR in radiographic objective response) that is subsequently confirmed to the date of first confirmed disease progression or death, whichever occurs first
measure: Progression free survival
time frame: Up to 24 weeks after last patient treated in a given cohort
description: The time from the first study treatment administration to the date of first documentation of progressive disease or death, whichever comes first
arm group label: Phase 1: cHl/DLBCL/PTCL
arm group type: Experimental
description: Isatuximab dose 1 or 2 depending on dose limiting toxicities (DLTs) observed and cemiplimab predefined dose
arm group label: Phase 2: Cohort A1: cHL, anti PD-1/PD-L1 naïve
arm group type: Experimental
description: Isatuximab and cemiplimab combination: Isatuximab dose determined in Phase 1 part of study and cemiplimab predefined dose
arm group label: Phase 2: Cohort A2: cHL, anti PD-1/PD-L1 progressor
arm group type: Experimental
description: Isatuximab and cemiplimab combination: Isatuximab dose determined in Phase 1 part of study and cemiplimab predefined dose
arm group label: Phase 2: Cohort B: DLBCL, anti PD-1/PD-L1 naïve
arm group type: Experimental
description: Isatuximab and cemiplimab combination: Isatuximab dose determined in Phase 1 part of study and cemiplimab predefined dose
arm group label: Phase 2: Cohort C: PTCL, anti PD-1/PD-L1 naïve
arm group type: Experimental
description: Isatuximab and cemiplimab combination: Isatuximab dose determined in Phase 1 part of study and cemiplimab predefined dose
intervention type: Drug
intervention name: isatuximab SAR650984
description: Pharmaceutical form: solution for infusion
Route of administration: intravenous
arm group label: Phase 1: cHl/DLBCL/PTCL
arm group label: Phase 2: Cohort A1: cHL, anti PD-1/PD-L1 naïve
arm group label: Phase 2: Cohort A2: cHL, anti PD-1/PD-L1 progressor
arm group label: Phase 2: Cohort B: DLBCL, anti PD-1/PD-L1 naïve
arm group label: Phase 2: Cohort C: PTCL, anti PD-1/PD-L1 naïve
other name: Sarclisa
intervention type: Drug
intervention name: cemiplimab REGN2810
description: Pharmaceutical form: solution for infusion
Route of administration: intravenous
arm group label: Phase 1: cHl/DLBCL/PTCL
arm group label: Phase 2: Cohort A1: cHL, anti PD-1/PD-L1 naïve
arm group label: Phase 2: Cohort A2: cHL, anti PD-1/PD-L1 progressor
arm group label: Phase 2: Cohort B: DLBCL, anti PD-1/PD-L1 naïve
arm group label: Phase 2: Cohort C: PTCL, anti PD-1/PD-L1 naïve
criteria: 
gender: All
minimum age: 12 Years
maximum age: N/A
healthy volunteers: No
last name: Clinical Sciences & Operations
role: Study Director
affiliation: Sanofi
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country: France
country: Italy
country: Korea, Republic of
country: Netherlands
country: Portugal
country: Spain
country: Taiwan
responsible party type: Sponsor
mesh term: Lymphoma
mesh term: Cemiplimab
sharing ipd: Yes
ipd description: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org
submitted: August 15, 2023
returned: September 12, 2023