<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/NCT04457778</url>
  </required_header>
  <id_info>
    <org_study_id>MS201430_0001</org_study_id>
    <nct_id>NCT04457778</nct_id>
  </id_info>
  <brief_title>First in Human Study of M6223</brief_title>
  <official_title>Phase I, First-in-Human, Open-Label, Multiple Ascending Dose Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Clinical Activity of M6223, an Inhibitor of TIGIT, as Single Agent and in Combination With Bintrafusp Alfa (Anti-PDL1/ TGFß Trap) in Participants With Metastatic or Locally Advanced Solid Unresectable Tumors</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>EMD Serono Research &amp; Development Institute, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Merck KGaA, Darmstadt, Germany</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>EMD Serono</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>
  </oversight_info>
  <brief_summary>
    <textblock>
      The main purpose of this study is to determine the safety, tolerability, pharmacokinetics&#xD;
      (PK), immunogenicity and (if observed) the maximum tolerated dose (MTD) of M6223 as a single&#xD;
      agent (Part 1A) for both the every 2 weeks (Q2W) regimen and the every 3 weeks (Q3W) regimen&#xD;
      and of M6223 combined with bintrafusp alfa (Part 1B) for Q2W regimen in participants with&#xD;
      metastatic or locally advanced solid unresectable tumors.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">July 10, 2020</start_date>
  <completion_date type="Anticipated">September 11, 2023</completion_date>
  <primary_completion_date type="Actual">June 23, 2023</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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Part 1A and 1B: Occurrence of Dose Limiting Toxicities (DLTs) During the DLT Observation Period (28 Days)</measure>
    <time_frame>Day 1 to Day 28</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Part IA and IB: Occurrence of Treatment-Emergent Adverse Events (TEAEs) and Treatment Related Adverse Events (TRAEs) According to the National Cancer Institute Common Terminology Criteria of Adverse Events (NCI-CTCAE) version 5</measure>
    <time_frame>Time from first study drug administration to final assessment at end of safety follow-up visit (up to a maximum of approximately 2 years)</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Part IA and IB: Occurrence of Treatment-Emergent Adverse Events (TEAEs) as per Severity and Deaths</measure>
    <time_frame>Time from first study drug administration to final assessment at end of safety follow-up visit (up to a maximum of approximately 2 years)</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Part IA and IB: Occurrence of Clinically Significant Change From Baseline in Clinical Laboratory Measures</measure>
    <time_frame>Time from baseline to final assessment at end of safety follow-up visit (up to a maximum of approximately 2 years)</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Part IA and IB: Occurrence of Clinically Significant Change From Baseline in Electrocardiogram Findings</measure>
    <time_frame>Time from baseline to final assessment at end of safety follow-up visit (up to a maximum of approximately 2 years)</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Part IA and IB: Occurrence of Clinically Significant Change From Baseline in Vital Signs</measure>
    <time_frame>Time from baseline to final assessment at end of safety follow-up visit (up to a maximum of approximately 2 years)</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Part IA and IB: Occurrence of Change From Baseline in Eastern Cooperative Oncology Group Performance Status</measure>
    <time_frame>Time from baseline to final assessment at end of safety follow-up visit (up to a maximum of approximately 2 years)</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Part 1A and Part 1B: Area Under the Serum Concentration-Time Curve From Time Zero to the Last Sampling Time (AUC 0-t) of M6223</measure>
    <time_frame>Pre-dose up to 14 days (in Q2W regimen) or 21 days (in Q3W regimen) post-dose of Cycles 1, 2, and 4 (Each cycle is of 14 days in Q2W regimen and each Cycle is of 21 days in Q3W regimen)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part 1A and Part 1B: Area Under the Serum Concentration-Time Curve From Time Zero to Infinity (AUC 0-inf) of M6223</measure>
    <time_frame>Pre-dose up to 14 days (in Q2W regimen) or 21 days (in Q3W regimen) post-dose of Cycles 1, 2, and 4 (Each cycle is of 14 days in Q2W regimen and each Cycle is of 21 days in Q3W regimen)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part 1A and Part 1B: Area Under Serum Concentration-Time Curve Over a Dosing Interval From Time Zero to Tau (τ) (AUCτ) of M6223</measure>
    <time_frame>Pre-dose up to 14 days (in Q2W regimen) or 21 days (in Q3W regimen) post-dose of Cycles 1, 2, and 4 (Each cycle is of 14 days in Q2W regimen and each Cycle is of 21 days in Q3W regimen)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part 1A and Part 1B: Maximum Observed Serum Concentration (Cmax) of M6223</measure>
    <time_frame>Pre-dose up to 14 days (in Q2W regimen) or 21 days (in Q3W regimen) post-dose of Cycles 1, 2, and 4 (Each cycle is of 14 days in Q2W regimen and each Cycle is of 21 days in Q3W regimen)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part 1A and Part 1B: Serum Concentration Observed Immediately Before Next Dosing (Ctrough) of M6223</measure>
    <time_frame>Pre-dose up to 14 days (in Q2W regimen) or 21 days (in Q3W regimen) post-dose of Cycles 1, 2, and 4 (Each cycle is of 14 days in Q2W regimen and each Cycle is of 21 days in Q3W regimen)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part 1A and Part 1B: Time to Reach Maximum Serum Concentration (Tmax) of M6223</measure>
    <time_frame>Pre-dose up to 14 days (in Q2W regimen) or 21 days (in Q3W regimen) post-dose of Cycles 1, 2, and 4 (Each cycle is of 14 days in Q2W regimen and each Cycle is of 21 days in Q3W regimen)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part 1A and Part 1B: Apparent Terminal Half-Life (t1/2) of M6223</measure>
    <time_frame>Pre-dose up to 14 days (in Q2W regimen) or 21 days (in Q3W regimen) post-dose of Cycles 1, 2, and 4 (Each cycle is of 14 days in Q2W regimen and each Cycle is of 21 days in Q3W regimen)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part 1A and Part 1B: Elimination Rate Constant (Lambda z) of M6223</measure>
    <time_frame>Pre-dose up to 14 days (in Q2W regimen) or 21 days (in Q3W regimen) post-dose of Cycles 1, 2, and 4 (Each cycle is of 14 days in Q2W regimen and each Cycle is of 21 days in Q3W regimen)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part 1B: Maximum Observed Serum Concentration (Cmax) of Bintrafusp alfa</measure>
    <time_frame>Pre-dose up to 14 days (in Q2W regimen) post-dose of Cycles 1, 2, and 4 (Each cycle is of 14 days in Q2W regimen)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part 1B: Serum Concentration Observed Immediately Before Next Dosing (Ctrough) of Bintrafusp alfa</measure>
    <time_frame>Pre-dose up to 14 days (in Q2W regimen) post-dose of Cycles 1, 2, and 4 (Each cycle is of 14 days in Q2W regimen)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part IA and 1B: Immunogenicity of M6223 Measured by Antidrug Antibody (ADA) Assays</measure>
    <time_frame>Pre-dose of Day 1 Cycle 1 (Each Cycle is of 14 days in Q2W regimen and 21 days in Q3W regimen) up to end of safety follow-up visit (up to a maximum of 2 years)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part 1B: Immunogenicity of Bintrafusp alfa Measured by Antidrug Antibody (ADA) Assays</measure>
    <time_frame>Pre-dose of Day 1 Cycle 1 (Each Cycle is of 14 days in Q2W regimen) up to end of safety follow-up visit (up to a maximum of 2 years)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part 1A and 1B: Change from Baseline in QT Interval</measure>
    <time_frame>From Day 1 Cycle 1 (Baseline) up to Day 1 Cycle 7 (Each Cycle is of 14 days in Q2W regimen and 21 days in Q3W regimen)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part 1A and IB: Best Overall Response According to Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1) Assessed as per Investigator</measure>
    <time_frame>From first study drug administration until documented disease progression or death due to any cause whichever occurs first, (approximately assessed up to 2 years)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part 1A and 1B: Duration of Response According to Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1) Assessed as per Investigator</measure>
    <time_frame>From first study drug administration until documented disease progression or death due to any cause whichever occurs first, (approximately assessed up to 2 years)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part 1A and 1B: Time to Tumor Response According to Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1) Assessed as per Investigator</measure>
    <time_frame>From first study drug administration until documented disease progression or death due to any cause whichever occurs first, (approximately assessed up to 2 years)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part 1A and 1B: Disease Control According to Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1) Assessed as per Investigator</measure>
    <time_frame>From first study drug administration until documented disease progression or death due to any cause whichever occurs first, (approximately assessed up to 2 years)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part 1A and 1B: Progression-free Survival Time According to Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1) Assessed as per Investigator</measure>
    <time_frame>From first study drug administration until documented disease progression or death due to any cause whichever occurs first, (approximately assessed up to 2 years)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part 1A and 1B: Overall Survival</measure>
    <time_frame>Time from first treatment to end of study (planned 12 months after last patient started treatment)</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">58</enrollment>
  <condition>Metastatic Solid Tumors</condition>
  <arm_group>
    <arm_group_label>Part 1A: M6223 Monotherapy</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Part1B: M6223 + Bintrafusp alfa</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>M6223</intervention_name>
    <description>Participants will receive an intravenous (IV) infusion of M6223 at escalated doses every 2 weeks (Q2W) or every 3 weeks (Q3W) on Day 1 of each Cycle (Each cycle is of 14 days) according to the recommendation of the SMC(Safety Monitoring Committee) until the maximum tolerated dose(MTD) has been reached or confirmed disease progression.</description>
    <arm_group_label>Part 1A: M6223 Monotherapy</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Bintrafusp alfa</intervention_name>
    <description>Participants will receive an IV infusion of bintrafusp alfa Q2W on Day 1 of each Cycle (Cycle is 14 days) until confirmed disease progression.</description>
    <arm_group_label>Part1B: M6223 + Bintrafusp alfa</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>M6223</intervention_name>
    <description>Participants will receive an IV infusion of M6223 at escalated doses Q2W on Day 1 of each Cycle (Each cycle is of 21 days) according to the recommendation of the SMC until the MTD has been reached or confirmed disease progression.</description>
    <arm_group_label>Part1B: M6223 + Bintrafusp alfa</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Participants have histologically or cytologically proven locally advanced or advanced&#xD;
             solid malignancies who are refractory to or have progressed under standard treatment&#xD;
             and have no other treatment options known to confer clinical benefit&#xD;
&#xD;
          -  Participants with Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0&#xD;
             to 1 at Screening&#xD;
&#xD;
          -  Participant has a formalin-fixed paraffin-embedded block containing tumor tissue or a&#xD;
             minimum of 15 (preferably 25) unstained tumor slides suitable for&#xD;
             immunohistochemistry-based staining of protein expression&#xD;
&#xD;
          -  Participants with life expectancy of at least 12 weeks&#xD;
&#xD;
          -  Participants with measurable disease according to Response Evaluation Criteria in&#xD;
             Solid Tumors version 1.1 (RECIST 1.1)&#xD;
&#xD;
          -  Adequate hematological, hepatic and renal function as defined in the protocol&#xD;
&#xD;
          -  Other protocol defined inclusion criteria may apply&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Participants with persisting toxicity related to prior therapy Grade greater than (&gt;)&#xD;
             1 National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE)&#xD;
             Version 5.0, however, alopecia, sensory neuropathy Grade less than or equal to (&lt;=) 2,&#xD;
             or other non-immune-related Grade &lt;= 2 not constituting a safety risk&#xD;
&#xD;
          -  Participants with prior organ transplantation including allogeneic stem cell&#xD;
             transplantation&#xD;
&#xD;
          -  Participants with prior toxicity related to an immune checkpoint inhibitor Grade&#xD;
             greater than equal to (&gt;=) 3 NCI-CTCAE Version 5.0 unless resolved to Grade &lt;= 1 prior&#xD;
             to study inclusion&#xD;
&#xD;
          -  Participants with current significant cardiac conduction abnormalities, including&#xD;
             corrected QT interval (QTcF, corrected with Fridericia formula) prolongation of &gt; 450&#xD;
             milli seconds (ms) on triplicate 12-lead ECG or impaired cardiovascular function,&#xD;
             ventricular tachycardia, hypokalemia or a history of paroxysmal atrial fibrillation,&#xD;
             serious cardiac arrhythmia and family history of sudden death or long QT syndrome&#xD;
&#xD;
          -  A history of vascular, cardiovascular or cerebrovascular disease like, cerebral&#xD;
             vascular accident/stroke (less than [&lt;] 6 months prior to enrollment), myocardial&#xD;
             infarction (&lt; 6 months prior to enrollment), unstable angina, congestive heart failure&#xD;
             (New York Heart Association Classification Class &gt;= II), deep vein thrombosis (&lt; 3&#xD;
             months prior to enrollment) or pulmonary thrombosis/embolism (&lt; 3 months prior to&#xD;
             enrollment)&#xD;
&#xD;
          -  Other protocol defined exclusion criteria may apply&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Medical Responsible</last_name>
    <role>Study Director</role>
    <affiliation>Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Sarah Cannon Research Institute</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37203</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>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>
    <facility>
      <name>Princess Margaret Cancer Centre</name>
      <address>
        <city>Toronto</city>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
    <country>United States</country>
  </location_countries>
  <removed_countries>
    <country>Germany</country>
  </removed_countries>
  <link>
    <url>https://clinicaltrials.emdgroup.com/en/trial-details/?id=MS201430_0001</url>
    <description>Trial Awareness and Transparency website</description>
  </link>
  <link>
    <url>https://medical.emdserono.com/en_US/home.html</url>
    <description>US Medical Information website, Medical Resources</description>
  </link>
  <link>
    <url>https://www.intrapidclinicaltrials.com/en</url>
    <description>INTR@PID Clinical Trial Program</description>
  </link>
  <verification_date>July 2023</verification_date>
  <study_first_submitted>June 30, 2020</study_first_submitted>
  <study_first_submitted_qc>June 30, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 7, 2020</study_first_posted>
  <last_update_submitted>August 7, 2023</last_update_submitted>
  <last_update_submitted_qc>August 7, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 8, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>M6223</keyword>
  <keyword>Bintrafusp alfa</keyword>
  <keyword>Metastatic Solid Tumors</keyword>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>We are committed to enhancing public health through responsible sharing of clinical trial data. Following approval of a new product or a new indication for an approved product in both the US and the European Union, the study sponsor and/or its affiliated companies will share study protocols, anonymized patient data and study level data, and redacted clinical study reports with qualified scientific and medical researchers, upon request, as necessary for conducting legitimate research. Further information on how to request data can be found on our website bit.ly/IPD21</ipd_description>
  </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/NCT04457778
org study id: MS201430_0001
nct id: NCT04457778
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
The main purpose of this study is to determine the safety, tolerability, pharmacokinetics
      (PK), immunogenicity and (if observed) the maximum tolerated dose (MTD) of M6223 as a single
      agent (Part 1A) for both the every 2 weeks (Q2W) regimen and the every 3 weeks (Q3W) regimen
      and of M6223 combined with bintrafusp alfa (Part 1B) for Q2W regimen in participants with
      metastatic or locally advanced solid unresectable tumors.
allocation: Non-Randomized
intervention model: Sequential Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Part 1A and 1B: Occurrence of Dose Limiting Toxicities (DLTs) During the DLT Observation Period (28 Days)
time frame: Day 1 to Day 28
measure: Part IA and IB: Occurrence of Treatment-Emergent Adverse Events (TEAEs) and Treatment Related Adverse Events (TRAEs) According to the National Cancer Institute Common Terminology Criteria of Adverse Events (NCI-CTCAE) version 5
time frame: Time from first study drug administration to final assessment at end of safety follow-up visit (up to a maximum of approximately 2 years)
measure: Part IA and IB: Occurrence of Treatment-Emergent Adverse Events (TEAEs) as per Severity and Deaths
time frame: Time from first study drug administration to final assessment at end of safety follow-up visit (up to a maximum of approximately 2 years)
measure: Part IA and IB: Occurrence of Clinically Significant Change From Baseline in Clinical Laboratory Measures
time frame: Time from baseline to final assessment at end of safety follow-up visit (up to a maximum of approximately 2 years)
measure: Part IA and IB: Occurrence of Clinically Significant Change From Baseline in Electrocardiogram Findings
time frame: Time from baseline to final assessment at end of safety follow-up visit (up to a maximum of approximately 2 years)
measure: Part IA and IB: Occurrence of Clinically Significant Change From Baseline in Vital Signs
time frame: Time from baseline to final assessment at end of safety follow-up visit (up to a maximum of approximately 2 years)
measure: Part IA and IB: Occurrence of Change From Baseline in Eastern Cooperative Oncology Group Performance Status
time frame: Time from baseline to final assessment at end of safety follow-up visit (up to a maximum of approximately 2 years)
measure: Part 1A and Part 1B: Area Under the Serum Concentration-Time Curve From Time Zero to the Last Sampling Time (AUC 0-t) of M6223
time frame: Pre-dose up to 14 days (in Q2W regimen) or 21 days (in Q3W regimen) post-dose of Cycles 1, 2, and 4 (Each cycle is of 14 days in Q2W regimen and each Cycle is of 21 days in Q3W regimen)
measure: Part 1A and Part 1B: Area Under the Serum Concentration-Time Curve From Time Zero to Infinity (AUC 0-inf) of M6223
time frame: Pre-dose up to 14 days (in Q2W regimen) or 21 days (in Q3W regimen) post-dose of Cycles 1, 2, and 4 (Each cycle is of 14 days in Q2W regimen and each Cycle is of 21 days in Q3W regimen)
measure: Part 1A and Part 1B: Area Under Serum Concentration-Time Curve Over a Dosing Interval From Time Zero to Tau (τ) (AUCτ) of M6223
time frame: Pre-dose up to 14 days (in Q2W regimen) or 21 days (in Q3W regimen) post-dose of Cycles 1, 2, and 4 (Each cycle is of 14 days in Q2W regimen and each Cycle is of 21 days in Q3W regimen)
measure: Part 1A and Part 1B: Maximum Observed Serum Concentration (Cmax) of M6223
time frame: Pre-dose up to 14 days (in Q2W regimen) or 21 days (in Q3W regimen) post-dose of Cycles 1, 2, and 4 (Each cycle is of 14 days in Q2W regimen and each Cycle is of 21 days in Q3W regimen)
measure: Part 1A and Part 1B: Serum Concentration Observed Immediately Before Next Dosing (Ctrough) of M6223
time frame: Pre-dose up to 14 days (in Q2W regimen) or 21 days (in Q3W regimen) post-dose of Cycles 1, 2, and 4 (Each cycle is of 14 days in Q2W regimen and each Cycle is of 21 days in Q3W regimen)
measure: Part 1A and Part 1B: Time to Reach Maximum Serum Concentration (Tmax) of M6223
time frame: Pre-dose up to 14 days (in Q2W regimen) or 21 days (in Q3W regimen) post-dose of Cycles 1, 2, and 4 (Each cycle is of 14 days in Q2W regimen and each Cycle is of 21 days in Q3W regimen)
measure: Part 1A and Part 1B: Apparent Terminal Half-Life (t1/2) of M6223
time frame: Pre-dose up to 14 days (in Q2W regimen) or 21 days (in Q3W regimen) post-dose of Cycles 1, 2, and 4 (Each cycle is of 14 days in Q2W regimen and each Cycle is of 21 days in Q3W regimen)
measure: Part 1A and Part 1B: Elimination Rate Constant (Lambda z) of M6223
time frame: Pre-dose up to 14 days (in Q2W regimen) or 21 days (in Q3W regimen) post-dose of Cycles 1, 2, and 4 (Each cycle is of 14 days in Q2W regimen and each Cycle is of 21 days in Q3W regimen)
measure: Part 1B: Maximum Observed Serum Concentration (Cmax) of Bintrafusp alfa
time frame: Pre-dose up to 14 days (in Q2W regimen) post-dose of Cycles 1, 2, and 4 (Each cycle is of 14 days in Q2W regimen)
measure: Part 1B: Serum Concentration Observed Immediately Before Next Dosing (Ctrough) of Bintrafusp alfa
time frame: Pre-dose up to 14 days (in Q2W regimen) post-dose of Cycles 1, 2, and 4 (Each cycle is of 14 days in Q2W regimen)
measure: Part IA and 1B: Immunogenicity of M6223 Measured by Antidrug Antibody (ADA) Assays
time frame: Pre-dose of Day 1 Cycle 1 (Each Cycle is of 14 days in Q2W regimen and 21 days in Q3W regimen) up to end of safety follow-up visit (up to a maximum of 2 years)
measure: Part 1B: Immunogenicity of Bintrafusp alfa Measured by Antidrug Antibody (ADA) Assays
time frame: Pre-dose of Day 1 Cycle 1 (Each Cycle is of 14 days in Q2W regimen) up to end of safety follow-up visit (up to a maximum of 2 years)
measure: Part 1A and 1B: Change from Baseline in QT Interval
time frame: From Day 1 Cycle 1 (Baseline) up to Day 1 Cycle 7 (Each Cycle is of 14 days in Q2W regimen and 21 days in Q3W regimen)
measure: Part 1A and IB: Best Overall Response According to Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1) Assessed as per Investigator
time frame: From first study drug administration until documented disease progression or death due to any cause whichever occurs first, (approximately assessed up to 2 years)
measure: Part 1A and 1B: Duration of Response According to Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1) Assessed as per Investigator
time frame: From first study drug administration until documented disease progression or death due to any cause whichever occurs first, (approximately assessed up to 2 years)
measure: Part 1A and 1B: Time to Tumor Response According to Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1) Assessed as per Investigator
time frame: From first study drug administration until documented disease progression or death due to any cause whichever occurs first, (approximately assessed up to 2 years)
measure: Part 1A and 1B: Disease Control According to Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1) Assessed as per Investigator
time frame: From first study drug administration until documented disease progression or death due to any cause whichever occurs first, (approximately assessed up to 2 years)
measure: Part 1A and 1B: Progression-free Survival Time According to Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1) Assessed as per Investigator
time frame: From first study drug administration until documented disease progression or death due to any cause whichever occurs first, (approximately assessed up to 2 years)
measure: Part 1A and 1B: Overall Survival
time frame: Time from first treatment to end of study (planned 12 months after last patient started treatment)
arm group label: Part 1A: M6223 Monotherapy
arm group type: Experimental
arm group label: Part1B: M6223 + Bintrafusp alfa
arm group type: Experimental
intervention type: Drug
intervention name: M6223
description: Participants will receive an intravenous (IV) infusion of M6223 at escalated doses every 2 weeks (Q2W) or every 3 weeks (Q3W) on Day 1 of each Cycle (Each cycle is of 14 days) according to the recommendation of the SMC(Safety Monitoring Committee) until the maximum tolerated dose(MTD) has been reached or confirmed disease progression.
arm group label: Part 1A: M6223 Monotherapy
intervention type: Drug
intervention name: Bintrafusp alfa
description: Participants will receive an IV infusion of bintrafusp alfa Q2W on Day 1 of each Cycle (Cycle is 14 days) until confirmed disease progression.
arm group label: Part1B: M6223 + Bintrafusp alfa
intervention type: Drug
intervention name: M6223
description: Participants will receive an IV infusion of M6223 at escalated doses Q2W on Day 1 of each Cycle (Each cycle is of 21 days) according to the recommendation of the SMC until the MTD has been reached or confirmed disease progression.
arm group label: Part1B: M6223 + Bintrafusp alfa
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Medical Responsible
role: Study Director
affiliation: Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
facility: 
facility: 
facility: 
facility: 
country: Canada
country: United States
country: Germany
url: https://clinicaltrials.emdgroup.com/en/trial-details/?id=MS201430_0001
description: Trial Awareness and Transparency website
url: https://medical.emdserono.com/en_US/home.html
description: US Medical Information website, Medical Resources
url: https://www.intrapidclinicaltrials.com/en
description: INTR@PID Clinical Trial Program
responsible party type: Sponsor
sharing ipd: No
ipd description: We are committed to enhancing public health through responsible sharing of clinical trial data. Following approval of a new product or a new indication for an approved product in both the US and the European Union, the study sponsor and/or its affiliated companies will share study protocols, anonymized patient data and study level data, and redacted clinical study reports with qualified scientific and medical researchers, upon request, as necessary for conducting legitimate research. Further information on how to request data can be found on our website bit.ly/IPD21