<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/NCT03787602</url>
  </required_header>
  <id_info>
    <org_study_id>KRT-232-103</org_study_id>
    <nct_id>NCT03787602</nct_id>
  </id_info>
  <brief_title>Navtemadlin (KRT-232) With or Without Anti-PD-1/Anti-PD-L1 for the Treatment of Patients With Merkel Cell Carcinoma</brief_title>
  <official_title>A Phase 1b/2, Open-Label Study Evaluating the Safety and Efficacy of KRT-232 in Patients With p53 Wild-Type (p53WT) Merkel Cell Carcinoma (MCC) Who Have Failed Anti-PD-1 or Anti-PD-L1 Immunotherapy, or in Combination With Avelumab in MCC Patients Who Are Anti-PD-1 or Anti-PD-L1 Treatment Naïve</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Kartos Therapeutics, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Kartos Therapeutics, Inc.</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study evaluates KRT-232, a novel oral small molecule inhibitor of MDM2, for the&#xD;
      treatment of patients with Merkel Cell Carcinoma (MCC) who have failed treatment with at&#xD;
      least one anti-PD-1 or anti-PD-L1 immunotherapy or in combination with avelumab in MCC&#xD;
      patients who are anti-PD-1 or anti-PD-L1 treatment naïve. Inhibition of MDM2 is a novel&#xD;
      mechanism of action in MCC.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">March 19, 2019</start_date>
  <completion_date type="Anticipated">August 2025</completion_date>
  <primary_completion_date type="Anticipated">November 2024</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>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Cohort 1 Part 1: To determine the KRT-232 RP2D.</measure>
    <time_frame>10 Weeks</time_frame>
    <description>The Safety Review Committee (SRC) will determine RP2D for expansion based on safety and tolerability of each arm.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Cohort 1 Part 2: To determine the objective response rate (ORR) in subjects with p53WT MCC who have failed anti-PD-1 or anti-PDL-1 immunotherapy</measure>
    <time_frame>10 Weeks</time_frame>
    <description>ORR will be assessed per RECIST criteria version 1.1 after all subjects have been treated at the RP2D of KRT 232 and completed the second response assessment.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Cohort 2 Part 1: To determine the KRT-232 RP2D in combination with avelumab</measure>
    <time_frame>28 Days</time_frame>
    <description>DLTs will be used to establish the MTD of KRT-232 in combination with avelumab. SRC will determine the RP2D based on the safety of combination of KRT-232 with avelumab.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Cohort 2 Part 2: To determine the objective response rate (ORR) in treatment-naïve subjects with p53WT MCC</measure>
    <time_frame>10 Weeks</time_frame>
    <description>ORR will be assessed per RECIST criteria version 1.1 after all 30 subjects have been treated at the RP2D of in combination with avelumab and have completed the second response assessment.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Cohort 3: To determine the confirmed overall response rate (ORR) based on IRC assessments in subjects with p53WT MCC are chemotherapy naive and have failed anti-PD-1/PD-L.</measure>
    <time_frame>10 Weeks</time_frame>
    <description>ORR will be assessed per RECIST criteria 1.1 by IRC.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Cohort 4: To determine the confirmed overall response rate (ORR) based on IRC assessments in subjects with p53WT MCC who have failed anti-PD-1 or anti-PDL-1 immunotherapy and have had least 1 line of prior chemotherapy.</measure>
    <time_frame>10 Weeks</time_frame>
    <description>ORR will be assessed per RECIST criteria 1.1 by IRC.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>To determine the confirmed ORR based on investigator assessment.</measure>
    <time_frame>1 year after last subject enrolled.</time_frame>
    <description>ORR will be assessed per RECIST criteria 1.1 by investigators.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To determine the duration of response (DoR)</measure>
    <time_frame>1 year after last subject enrolled</time_frame>
    <description>Time from documentation of response (CR or PR as determined by RECIST 1.1) until disease progression.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To determine Progression-free survival (PFS)</measure>
    <time_frame>1 year after last subject enrolled</time_frame>
    <description>Time from initial treatment until disease progression.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To determine overall survival (OS)</measure>
    <time_frame>1 year after last subject enrolled</time_frame>
    <description>Time from initial treatment until death from any cause.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To determine clinical benefit rate (CBR)</measure>
    <time_frame>1 year after last subject enrolled.</time_frame>
    <description>PR, CR or stable disease that last at least 10 weeks, per IRC or investigator assessment.</description>
  </secondary_outcome>
  <number_of_arms>11</number_of_arms>
  <enrollment type="Anticipated">115</enrollment>
  <condition>Merkel Cell Carcinoma</condition>
  <arm_group>
    <arm_group_label>Cohort 1, Arm 1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>KRT-232 will be administered orally, once daily (QD) on Days 1-7 in a 21-day cycle.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 1, Arm 1b</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>KRT-232 will be administered orally, once daily (QD) on Days 1-5 in a 23-day cycle.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 1, Arm 2b</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>KRT-232 will be administered orally, once daily (QD) on Days 1-5 in a 28-day cycle.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 1, Arm 3</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>KRT-232 will be administered orally, once daily (QD) on Days 1-7 in a 21-day cycle.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 1, Arm 5</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>KRT-232 will be administered orally, once daily (QD) on Days 1-7 in a 28-day cycle.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 1 Expansion</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>KRT-232 will be administered orally, once daily (QD) per Cohort 1 RP2D dose and schedule.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 2, Arm 1 KRT-232 in combination with avelumab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>KRT-232 will be administered orally, once daily (QD) on Days 1-5, in combination with avelumab 800 mg IV on Day 1 and 15 in a 28-day cycle.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 2, Arm 2 KRT-232 in combination with avelumab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>KRT-232 will be administered orally, once daily (QD) on Days 1-7, in combination with avelumab 800 mg IV on Day 1 and 15 in a 28-day cycle.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 2 Expansion</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>KRT-232 will be administered orally, once daily (QD) per RP2D dose and schedule, in combination with avelumab 800 mg IV on Day 1 and 15 in a 28-day cycle.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 3</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>KRT-232 will be administered orally, once daily (QD) per Cohort 1 RP2D dose and schedule.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 4</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>KRT-232 will be administered orally, once daily (QD) per Cohort 1 RP2D dose and schedule.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>KRT-232</intervention_name>
    <description>KRT-232 is an experimental MDM2 anticancer drug taken by mouth.</description>
    <arm_group_label>Cohort 1 Expansion</arm_group_label>
    <arm_group_label>Cohort 1, Arm 1</arm_group_label>
    <arm_group_label>Cohort 1, Arm 1b</arm_group_label>
    <arm_group_label>Cohort 1, Arm 2b</arm_group_label>
    <arm_group_label>Cohort 1, Arm 3</arm_group_label>
    <arm_group_label>Cohort 1, Arm 5</arm_group_label>
    <arm_group_label>Cohort 2 Expansion</arm_group_label>
    <arm_group_label>Cohort 2, Arm 1 KRT-232 in combination with avelumab</arm_group_label>
    <arm_group_label>Cohort 2, Arm 2 KRT-232 in combination with avelumab</arm_group_label>
    <arm_group_label>Cohort 3</arm_group_label>
    <arm_group_label>Cohort 4</arm_group_label>
    <other_name>navtemadlin</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Avelumab</intervention_name>
    <description>Avelumab is a PD-L1 blocking antibody anticancer drug administered by intravenous infusion.</description>
    <arm_group_label>Cohort 2 Expansion</arm_group_label>
    <arm_group_label>Cohort 2, Arm 1 KRT-232 in combination with avelumab</arm_group_label>
    <arm_group_label>Cohort 2, Arm 2 KRT-232 in combination with avelumab</arm_group_label>
    <other_name>Bavencio</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  For Cohort 1, 3 and 4 patients must have failed treatment with at least one PD-1&#xD;
             inhibitor or PD-L1 inhibitor for metastatic MCC&#xD;
&#xD;
          -  For Cohort 2, patients must not have received any anti-PD-1 or anti-PD-L1 therapy&#xD;
&#xD;
          -  For Cohort 3, patients must not have received any prior chemotherapy&#xD;
&#xD;
          -  For Cohort 4, patients must have received at least one prior line of chemotherapy&#xD;
&#xD;
          -  ECOG performance status of 0 to 1&#xD;
&#xD;
          -  Histologically confirmed MCC. Disease must be measurable, with at least 1 measurable&#xD;
             lesion by RECIST 1.1&#xD;
&#xD;
          -  MCC expressing p53WT based on any CLIA or test approved by local health authority or a&#xD;
             validated test (Cohort 1 and 2)&#xD;
&#xD;
          -  MCC expressing p53WT based Central Lab test (Cohort 3 and 4)&#xD;
&#xD;
          -  Adequate hematological, hepatic, and renal functions&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  For Cohort 2, subjects must not have autoimmune disease, medical conditions requiring&#xD;
             systemic immunosuppression, prior stem cell transplant, or active infection with HBV&#xD;
             or HCV.&#xD;
&#xD;
          -  Patients previously treated with MDM2 antagonist therapies or p53-directed therapies&#xD;
&#xD;
          -  History of major organ transplant&#xD;
&#xD;
          -  Patients with known central nervous system (CNS) metastases that are previously&#xD;
             untreated&#xD;
&#xD;
          -  Grade 2 or higher QTc prolongation (&gt;480 milli-seconds per NCI-CTCAE criteria, version&#xD;
             5.0)&#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_contact>
    <last_name>John Mei</last_name>
    <phone>650-542-0136</phone>
    <email>jmei@kartosthera.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Emily Houlihan</last_name>
    <phone>401-954-8042</phone>
    <email>ehoulihan@kartosthera.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>University of Colorado Anschutz Medical Campus</name>
      <address>
        <city>Aurora</city>
        <state>Colorado</state>
        <zip>80045</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Miami Cancer Institute</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33176</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Moffitt</name>
      <address>
        <city>Tampa</city>
        <state>Florida</state>
        <zip>33612</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Northwestern Memorial Hospital</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60612</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Norton Healthcare</name>
      <address>
        <city>Louisville</city>
        <state>Kentucky</state>
        <zip>40202</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Norton Cancer Institute Research</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Massachusetts General Hospital</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02114</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Dana-Farber Cancer Institute</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02215-5418</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>University of Michigan</name>
      <address>
        <city>Ann Arbor</city>
        <state>Michigan</state>
        <zip>48109</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Memorial Sloan-Kettering Cancer Center</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10021</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Mount Sinai Hospital</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10029</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Fox Chase Cancer Center</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19111-2434</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>UPMC Hillman Cancer Center</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <zip>15232</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>University of Texas MD Anderson</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Inova Health Care Services</name>
      <address>
        <city>Fairfax</city>
        <state>Virginia</state>
        <zip>22031</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Princess Alexandra Hospital Oncology</name>
      <address>
        <city>Woolloongabba</city>
        <country>Australia</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Centro Catarinense de Pesquisa (CECAP) - Hospital Santa Catarina de Blumenau</name>
      <address>
        <city>Blumenau</city>
        <country>Brazil</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Instituto Nacional do Cancer</name>
      <address>
        <city>Brasília</city>
        <country>Brazil</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Centro Intergado de Oncologia</name>
      <address>
        <city>Curitiba</city>
        <country>Brazil</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Centro de Pesquisa Clinica em Oncologia</name>
      <address>
        <city>Ijuí</city>
        <country>Brazil</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Clinica De Neoplasias Litoral</name>
      <address>
        <city>Itajai</city>
        <country>Brazil</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Hospital Paulistano</name>
      <address>
        <city>São Paulo</city>
        <country>Brazil</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Princess Margaret Cancer Centre</name>
      <address>
        <city>Toronto</city>
        <country>Canada</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>CHU de Bordeaux- Hopital Saint-Andre</name>
      <address>
        <city>Bordeaux</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>AP-HP Universite Paris Saclay</name>
      <address>
        <city>Gif-sur-Yvette</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>CHU de Lille</name>
      <address>
        <city>Lille</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>CHU Lyon-Sud</name>
      <address>
        <city>Lyon</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Hôpital de la Timone. Aix-Marseille Université</name>
      <address>
        <city>Marseille</city>
        <zip>Cedex 5</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>CHU Montpellier</name>
      <address>
        <city>Montpellier</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>CHU de Nantes</name>
      <address>
        <city>Nantes</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Hôpital Saint Louis - APHP</name>
      <address>
        <city>Paris</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>CHU de Tours</name>
      <address>
        <city>Tours</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Vivantes Network for Health Gmb, Neukölln Clinic</name>
      <address>
        <city>Berlin</city>
        <country>Germany</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Universitätsklinikum Erlangen</name>
      <address>
        <city>Erlangen</city>
        <country>Germany</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Universitätsklinikum Essen (AöR)</name>
      <address>
        <city>Essen</city>
        <country>Germany</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Nationales Centrum für Tumorerkrankungen NCT</name>
      <address>
        <city>Heidelberg</city>
        <country>Germany</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Uniklinik Koln</name>
      <address>
        <city>Köln</city>
        <country>Germany</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Universitätsklinik Rostock</name>
      <address>
        <city>Rostock</city>
        <country>Germany</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Universitats-Hautklinik Tubingen</name>
      <address>
        <city>Tübingen</city>
        <country>Germany</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Institute for Cancer Research and Treatment</name>
      <address>
        <city>Candiolo</city>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Istituto Nazionale Tumori IRCCS Fondazione Pascale</name>
      <address>
        <city>Napoli</city>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>AUSL della Romagna</name>
      <address>
        <city>Ravenna</city>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>AOUS Le Scotte</name>
      <address>
        <city>Siena</city>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>OSP Civile Maggiore Borgo Trento</name>
      <address>
        <city>Verona</city>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>National Cancer Center</name>
      <address>
        <city>Goyang-si</city>
        <country>Korea, Republic of</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Seoul National University Hospital</name>
      <address>
        <city>Seoul</city>
        <country>Korea, Republic of</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Severance Hospital Yonsei University Health System</name>
      <address>
        <city>Seoul</city>
        <country>Korea, Republic of</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>University Medical Center Groningen</name>
      <address>
        <city>Groningen</city>
        <country>Netherlands</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Hospital Duran i Reynals</name>
      <address>
        <city>Barcelona</city>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Hospital General Universitario Gregorio Marañn (Madrid)</name>
      <address>
        <city>Madrid</city>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Complejo Hospitalario de Navarra</name>
      <address>
        <city>Pamplona</city>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Fundacio Investigao Hospital General Universitario de Valencia</name>
      <address>
        <city>Valencia</city>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location_countries>
    <country>Australia</country>
    <country>Brazil</country>
    <country>Canada</country>
    <country>France</country>
    <country>Germany</country>
    <country>Italy</country>
    <country>Korea, Republic of</country>
    <country>Netherlands</country>
    <country>Spain</country>
    <country>United States</country>
  </location_countries>
  <verification_date>February 2023</verification_date>
  <study_first_submitted>December 6, 2018</study_first_submitted>
  <study_first_submitted_qc>December 21, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 26, 2018</study_first_posted>
  <last_update_submitted>February 28, 2023</last_update_submitted>
  <last_update_submitted_qc>February 28, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">March 2, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>navtemadlin (KRT-232)</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Carcinoma, Merkel Cell</mesh_term>
    <mesh_term>Carcinoma</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Avelumab</mesh_term>
  </intervention_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/NCT03787602
org study id: KRT-232-103
nct id: NCT03787602
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
This study evaluates KRT-232, a novel oral small molecule inhibitor of MDM2, for the
      treatment of patients with Merkel Cell Carcinoma (MCC) who have failed treatment with at
      least one anti-PD-1 or anti-PD-L1 immunotherapy or in combination with avelumab in MCC
      patients who are anti-PD-1 or anti-PD-L1 treatment naïve. Inhibition of MDM2 is a novel
      mechanism of action in MCC.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Cohort 1 Part 1: To determine the KRT-232 RP2D.
time frame: 10 Weeks
description: The Safety Review Committee (SRC) will determine RP2D for expansion based on safety and tolerability of each arm.
measure: Cohort 1 Part 2: To determine the objective response rate (ORR) in subjects with p53WT MCC who have failed anti-PD-1 or anti-PDL-1 immunotherapy
time frame: 10 Weeks
description: ORR will be assessed per RECIST criteria version 1.1 after all subjects have been treated at the RP2D of KRT 232 and completed the second response assessment.
measure: Cohort 2 Part 1: To determine the KRT-232 RP2D in combination with avelumab
time frame: 28 Days
description: DLTs will be used to establish the MTD of KRT-232 in combination with avelumab. SRC will determine the RP2D based on the safety of combination of KRT-232 with avelumab.
measure: Cohort 2 Part 2: To determine the objective response rate (ORR) in treatment-naïve subjects with p53WT MCC
time frame: 10 Weeks
description: ORR will be assessed per RECIST criteria version 1.1 after all 30 subjects have been treated at the RP2D of in combination with avelumab and have completed the second response assessment.
measure: Cohort 3: To determine the confirmed overall response rate (ORR) based on IRC assessments in subjects with p53WT MCC are chemotherapy naive and have failed anti-PD-1/PD-L.
time frame: 10 Weeks
description: ORR will be assessed per RECIST criteria 1.1 by IRC.
measure: Cohort 4: To determine the confirmed overall response rate (ORR) based on IRC assessments in subjects with p53WT MCC who have failed anti-PD-1 or anti-PDL-1 immunotherapy and have had least 1 line of prior chemotherapy.
time frame: 10 Weeks
description: ORR will be assessed per RECIST criteria 1.1 by IRC.
measure: To determine the confirmed ORR based on investigator assessment.
time frame: 1 year after last subject enrolled.
description: ORR will be assessed per RECIST criteria 1.1 by investigators.
measure: To determine the duration of response (DoR)
time frame: 1 year after last subject enrolled
description: Time from documentation of response (CR or PR as determined by RECIST 1.1) until disease progression.
measure: To determine Progression-free survival (PFS)
time frame: 1 year after last subject enrolled
description: Time from initial treatment until disease progression.
measure: To determine overall survival (OS)
time frame: 1 year after last subject enrolled
description: Time from initial treatment until death from any cause.
measure: To determine clinical benefit rate (CBR)
time frame: 1 year after last subject enrolled.
description: PR, CR or stable disease that last at least 10 weeks, per IRC or investigator assessment.
arm group label: Cohort 1, Arm 1
arm group type: Experimental
description: KRT-232 will be administered orally, once daily (QD) on Days 1-7 in a 21-day cycle.
arm group label: Cohort 1, Arm 1b
arm group type: Experimental
description: KRT-232 will be administered orally, once daily (QD) on Days 1-5 in a 23-day cycle.
arm group label: Cohort 1, Arm 2b
arm group type: Experimental
description: KRT-232 will be administered orally, once daily (QD) on Days 1-5 in a 28-day cycle.
arm group label: Cohort 1, Arm 3
arm group type: Experimental
description: KRT-232 will be administered orally, once daily (QD) on Days 1-7 in a 21-day cycle.
arm group label: Cohort 1, Arm 5
arm group type: Experimental
description: KRT-232 will be administered orally, once daily (QD) on Days 1-7 in a 28-day cycle.
arm group label: Cohort 1 Expansion
arm group type: Experimental
description: KRT-232 will be administered orally, once daily (QD) per Cohort 1 RP2D dose and schedule.
arm group label: Cohort 2, Arm 1 KRT-232 in combination with avelumab
arm group type: Experimental
description: KRT-232 will be administered orally, once daily (QD) on Days 1-5, in combination with avelumab 800 mg IV on Day 1 and 15 in a 28-day cycle.
arm group label: Cohort 2, Arm 2 KRT-232 in combination with avelumab
arm group type: Experimental
description: KRT-232 will be administered orally, once daily (QD) on Days 1-7, in combination with avelumab 800 mg IV on Day 1 and 15 in a 28-day cycle.
arm group label: Cohort 2 Expansion
arm group type: Experimental
description: KRT-232 will be administered orally, once daily (QD) per RP2D dose and schedule, in combination with avelumab 800 mg IV on Day 1 and 15 in a 28-day cycle.
arm group label: Cohort 3
arm group type: Experimental
description: KRT-232 will be administered orally, once daily (QD) per Cohort 1 RP2D dose and schedule.
arm group label: Cohort 4
arm group type: Experimental
description: KRT-232 will be administered orally, once daily (QD) per Cohort 1 RP2D dose and schedule.
intervention type: Drug
intervention name: KRT-232
description: KRT-232 is an experimental MDM2 anticancer drug taken by mouth.
arm group label: Cohort 1 Expansion
arm group label: Cohort 1, Arm 1
arm group label: Cohort 1, Arm 1b
arm group label: Cohort 1, Arm 2b
arm group label: Cohort 1, Arm 3
arm group label: Cohort 1, Arm 5
arm group label: Cohort 2 Expansion
arm group label: Cohort 2, Arm 1 KRT-232 in combination with avelumab
arm group label: Cohort 2, Arm 2 KRT-232 in combination with avelumab
arm group label: Cohort 3
arm group label: Cohort 4
other name: navtemadlin
intervention type: Drug
intervention name: Avelumab
description: Avelumab is a PD-L1 blocking antibody anticancer drug administered by intravenous infusion.
arm group label: Cohort 2 Expansion
arm group label: Cohort 2, Arm 1 KRT-232 in combination with avelumab
arm group label: Cohort 2, Arm 2 KRT-232 in combination with avelumab
other name: Bavencio
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: John Mei
phone: 650-542-0136
email: jmei@kartosthera.com
last name: Emily Houlihan
phone: 401-954-8042
email: ehoulihan@kartosthera.com
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Active, not recruiting
facility: 
status: Recruiting
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status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
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status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
country: Australia
country: Brazil
country: Canada
country: France
country: Germany
country: Italy
country: Korea, Republic of
country: Netherlands
country: Spain
country: United States
responsible party type: Sponsor
mesh term: Carcinoma, Merkel Cell
mesh term: Carcinoma
mesh term: Avelumab