<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/NCT04418661</url>
  </required_header>
  <id_info>
    <org_study_id>TCD16210</org_study_id>
    <secondary_id>U1111-1244-2555</secondary_id>
    <secondary_id>2020-000436-22</secondary_id>
    <nct_id>NCT04418661</nct_id>
  </id_info>
  <brief_title>Safety and Efficacy Study of SAR442720 in Combination With Other Agents in Advanced Malignancies</brief_title>
  <official_title>A Phase 1/2, Open-label, Multicenter, Dose Escalation and Dose Expansion Study of SAR442720 in Combination With Other Agents in Participants With Advanced Malignancies</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Sanofi</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Revolution Medicines, Inc.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Mirati Therapeutics Inc.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Sanofi</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>
      Primary Objectives:&#xD;
&#xD;
        -  Part 1&#xD;
&#xD;
        -  To characterize the safety and tolerability of SAR442720 in combination with&#xD;
           pembrolizumab in participants with advanced solid tumors.&#xD;
&#xD;
        -  To define the MTD and RP2D for the combination of SAR442720 and pembrolizumab in&#xD;
           participants with solid tumors.&#xD;
&#xD;
        -  Part 2&#xD;
&#xD;
        -  To determine the anti-tumor activity of SAR442720 in combination with pembrolizumab.&#xD;
&#xD;
        -  Part 3A&#xD;
&#xD;
        -  To define the MTD and RP2D for the combination of SAR442720 and adagrasib in&#xD;
           participants with KRAS G12C NSCLC&#xD;
&#xD;
        -  To characterize the safety and tolerability of SAR442720 in combination with adagrasib&#xD;
           in participants with KRAS G12C NSCLC&#xD;
&#xD;
        -  Part 3B&#xD;
&#xD;
        -  To determine the anti-tumor activity of SAR442720 in combination with adagrasib in&#xD;
           participants with KRAS G12C NSCLC&#xD;
&#xD;
        -  Part 4&#xD;
&#xD;
        -  To evaluate the impact of food on the PK of SAR442720 when dosed with pembrolizumab.&#xD;
&#xD;
        -  To evaluate the impact of the formulations (formulation 1 and formulation 2) on the PK&#xD;
           of SAR442720 when dosed with pembrolizumab.&#xD;
&#xD;
      Secondary Objectives:&#xD;
&#xD;
        -  Part 1&#xD;
&#xD;
        -  To assess the PK of SAR442720 with pembrolizumab, and the PK of pembrolizumab with&#xD;
           SAR442720.&#xD;
&#xD;
        -  To estimate the anti-tumor effects of SAR442720 with pembrolizumab.&#xD;
&#xD;
        -  Part 2&#xD;
&#xD;
        -  To assess the safety profile of SAR442720 combined with pembrolizumab.&#xD;
&#xD;
        -  To assess other indicators of anti-tumor activity.&#xD;
&#xD;
        -  To assess the PK of SAR442720 with pembrolizumab, and the PK of pembrolizumab with&#xD;
           SAR442720.&#xD;
&#xD;
        -  Part 3A&#xD;
&#xD;
        -  To characterize the PK of SAR442720 with adagrasib, and the PK of adagrasib with&#xD;
           SAR442720.&#xD;
&#xD;
        -  To estimate the anti-tumor effects of SAR442720 with adagrasib&#xD;
&#xD;
        -  Part 3B&#xD;
&#xD;
        -  To assess the safety profile of SAR442720 with adagrasib in participants with KRAS G12C&#xD;
           NSCLC.&#xD;
&#xD;
        -  To assess other indicators of anti-tumor activity.&#xD;
&#xD;
        -  To assess the PK of SAR442720 with adagrasib, and the PK of adagrasib with SAR442720.&#xD;
&#xD;
        -  Part 4&#xD;
&#xD;
        -  To assess the safety and tolerability of SAR442720 formulations with pembrolizumab&#xD;
&#xD;
        -  To estimate the anti-tumor effects of SAR442720 with pembrolizumab.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This open label Phase 1 multicenter study is designed to evaluate the safety and maximum&#xD;
      tolerated dose (MTD) and recommended phase 2 dose (RP2D) of SAR442720 in combination with&#xD;
      pembrolizumab in participants with solid tumors in Part 1.&#xD;
&#xD;
      In Part 2, in the expansion cohort (Cohort A) we will assess the antitumor activity and&#xD;
      safety of SAR442720 combined with pembrolizumab in participants with metastatic 1L lung&#xD;
      cancer.&#xD;
&#xD;
      In Part 3, we will evaluate the safety, MTD, RP2D and antitumor activity of SAR442720 in&#xD;
      combination with adagrasib in participants with lung cancer and KRAS G12C mutation.&#xD;
&#xD;
      In Part 4, we will evaluate the impact of the formulations (formulation 1 and formulation 2)&#xD;
      and of the food on the PK of SAR442720 when dosed in combination with pembrolizumab. The&#xD;
      expected duration of study intervention for participants may vary, based on progression date;&#xD;
      median expected duration of study per participant is estimated to be about 10 months in Part&#xD;
      1, Part 3 and Part 4 (up to 1 month for screening, a median of 6 months for treatment, and a&#xD;
      median of 3 months for long term follow-up) and in Part 2 16 months (up to 1 month for&#xD;
      screening, a median of 12 months for treatment and a median of 3 months for long term follow&#xD;
      up.)&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">June 9, 2020</start_date>
  <completion_date type="Anticipated">July 15, 2024</completion_date>
  <primary_completion_date type="Anticipated">July 15, 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>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>Incidence of Adverse Events (AEs) SAR442720 and pembrolizumab</measure>
    <time_frame>21 days</time_frame>
    <description>Part 1:&#xD;
Incidence, nature, and severity of treatment emergent AEs and serious adverse events (SAEs), graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0 for the combination of SAR442720 and pembrolizumab.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidence of study-drug related Dose Limiting Toxicities (DLTs)</measure>
    <time_frame>up to 2 years</time_frame>
    <description>Part 1 and 3A:&#xD;
Incidence of study drug-related dose-limiting toxicities (DLTs) in Cycle 1.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Objective Response Rate (ORR)</measure>
    <time_frame>up to 2 years</time_frame>
    <description>Part 2 and 3B:&#xD;
Objective response rate defined as the proportion of participants who have a confirmed CR or partial response (PR) determined by investigator, per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidence of Adverse Events (AEs) SAR442720 and adagrasib</measure>
    <time_frame>up to 2 years</time_frame>
    <description>Part 3A:&#xD;
Incidence, nature, and severity of TEAEs and SAEs, graded according to NCI CTCAEv5.0 for the combination of SAR442720 and adagrasib.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Part 4: Plasma concentrations of SAR442720 in combination with pembrolizumab under impact of food</measure>
    <time_frame>up to 2 years</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Part 1 and 2: Plasma concentrations of SAR442720</measure>
    <time_frame>up to 2 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part 1 and 2: Serum concentration of pembrolizumab</measure>
    <time_frame>up to 2 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Objective response rate (ORR) Part 1 and Part 4</measure>
    <time_frame>up to 2 years</time_frame>
    <description>Part 1 and Part 4:&#xD;
Objective response rate of SAR442720 and pembrolizumab in all participants. ORR of combination therapy with SAR442720 and pembrolizumab will be based on Response Evaluation Criteria in Solid Tumors (RECIST) v1.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of response (DoR)</measure>
    <time_frame>up to 2 years</time_frame>
    <description>Part 1 and Part 2 and 3B:&#xD;
Duration of response per RECIST v1.1 is defined as the interval from the first documentation of CR (complete response) or PR (partial response) to the earlier of the first documentation of definitive disease progression or death due to any cause, whichever occurs first.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of Adverse Events</measure>
    <time_frame>up to 2 years</time_frame>
    <description>Part 2 and 3B and Part 4:&#xD;
Incidence, nature, and severity of treatment emergent adverse events (TEAEs) and serious adverse events (SAEs) graded according to the NCI CTCAE v5 for the combination of SAR442720 and pembrolizumab.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Response (TTR)</measure>
    <time_frame>up to 2 years</time_frame>
    <description>Part 2 and 3B:&#xD;
Time to response (TTR) defined as the time from the first administration of investigational medicinal product (IMP) to the first documented evidence of PR or CR determined by the Investigator per RECIST v1.1 (for NSCLC).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clinical Benefit Rate (CBR)</measure>
    <time_frame>up to 2 years</time_frame>
    <description>Part 2 and 3B:&#xD;
Clinical benefit rate (CBR) including confirmed CR or PR at any time or stable disease (SD) of at least 6 months (determined by the Investigator per RECIST v1.1.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Disease Control Rate (DCR)</measure>
    <time_frame>up to 2 years</time_frame>
    <description>Part 2 and 3B:&#xD;
Disease control rate (DCR) including confirmed CR or PR or stable disease (SD) as determined by the Investigator per RECIST v1.1.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression free survival (PFS)</measure>
    <time_frame>up to 2 years</time_frame>
    <description>Part 2 and 3B:&#xD;
Progression free survival (PFS), defined as the time from the date of first IMP administration to the date of the first documented disease progression determined by the Investigator as per RECIST v1.1 or death due to any cause, whichever occurs first.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part 3A: Plasma concentrations of SAR442720</measure>
    <time_frame>up to 2 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part 3A: Plasma concentrations of adagrasib</measure>
    <time_frame>up to 2 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Objective Response Rate (ORR) of SAR442720 and adagrasib</measure>
    <time_frame>up to 2 years</time_frame>
    <description>Part 3A:&#xD;
ORR of SAR442720 and adagrasib in all participants. ORR of combination therapy with SAR442720 and adagrasib will be based on RECIST v1.1.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of Response (DOR) of SAR442720 and adagrasib</measure>
    <time_frame>up to 2 years</time_frame>
    <description>Part 3:&#xD;
DOR of SAR442720 and adagrasib in all participants. ORR of combination therapy with SAR442720 and adagrasib will be based on RECIST v1.1.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part 3B: Plasma concentrations of SAR442720 and adagrasib</measure>
    <time_frame>up to 2 years</time_frame>
  </secondary_outcome>
  <number_of_arms>6</number_of_arms>
  <enrollment type="Actual">65</enrollment>
  <condition>Metastatic Neoplasm</condition>
  <arm_group>
    <arm_group_label>SAR442720 + Pembrolizumab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Part 1:&#xD;
SAR442720 (also known as RMC-4630) will be administered orally twice a week (BIW) followed by pembrolizumab which is given intravenously (IV) once every 3 weeks (Q3W). The dose of SAR442720 will be escalated or de-escalated depending on the emerging safety data of the combination.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>SAR442720 + Pembrolizumab: Non-small cell lung cancer with Tumor proportion score &gt; 50%</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Part 2:&#xD;
SAR442720 dose will be administered orally in combination with Pembrolizumab which is given by IV infusion once every 3 weeks (Q3W) or once every 6 weeks (Q6W)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>SAR442720 + Pembrolizumab: Non-small cell lung cancer with Tumor proportion score 1-49%</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Part 2:&#xD;
SAR442720 dose will be administered orally in combination with Pembrolizumab which is given by IV infusion once every 3 weeks (Q3W) or once every 6 weeks (Q6W)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>SAR444270 + adagrasib: Dose Escalation</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Part 3A; SAR442720 and adagrasib will be administered orally on a continuous basis.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>SAR444270 + adagrasib: Dose Expansion</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Part 3B:&#xD;
Once SAR442720 dose is confirmed in Part 3A SAR442720 and adagrasib will be administered orally on a continuous basis.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>SAR442720 + Pembrolizumab continuous</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Part 4:&#xD;
SAR442720 will be administered orally in combination with Pembrolizumab which is given by IV infusion once every 3 weeks (Q3W) or once every 6 weeks (Q6W)</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>SAR442720</intervention_name>
    <description>Pharmaceutical form: Varies Route of administration: Varies</description>
    <arm_group_label>SAR442720 + Pembrolizumab</arm_group_label>
    <arm_group_label>SAR442720 + Pembrolizumab continuous</arm_group_label>
    <arm_group_label>SAR442720 + Pembrolizumab: Non-small cell lung cancer with Tumor proportion score 1-49%</arm_group_label>
    <arm_group_label>SAR442720 + Pembrolizumab: Non-small cell lung cancer with Tumor proportion score &gt; 50%</arm_group_label>
    <arm_group_label>SAR444270 + adagrasib: Dose Escalation</arm_group_label>
    <arm_group_label>SAR444270 + adagrasib: Dose Expansion</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Pembrolizumab</intervention_name>
    <description>Pharmaceutical form:Sterile Lyophilized powder for reconstitution Route of administration: Infusion</description>
    <arm_group_label>SAR442720 + Pembrolizumab</arm_group_label>
    <arm_group_label>SAR442720 + Pembrolizumab continuous</arm_group_label>
    <arm_group_label>SAR442720 + Pembrolizumab: Non-small cell lung cancer with Tumor proportion score 1-49%</arm_group_label>
    <arm_group_label>SAR442720 + Pembrolizumab: Non-small cell lung cancer with Tumor proportion score &gt; 50%</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Adagrasib</intervention_name>
    <description>Pharmaceutical form:Sterile Tablet Route of administration: Oral</description>
    <arm_group_label>SAR444270 + adagrasib: Dose Escalation</arm_group_label>
    <arm_group_label>SAR444270 + adagrasib: Dose Expansion</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Participants must be ≥ 18 years of age.&#xD;
&#xD;
          -  Histologically proven diagnosis of advanced solid tumors.&#xD;
&#xD;
          -  Participants must have one or more of the following molecular aberrations (Part 1):&#xD;
             KRAS mutations and amplifications, BRAF Class 3 mutations, or NF1 LOF mutations.&#xD;
&#xD;
          -  Participants must have following molecular aberration (Part 3A and 3B): - KRAS G12C&#xD;
             mutation.&#xD;
&#xD;
          -  At least 1 measurable disease per RECIST 1.1 criteria.&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status 0-1.&#xD;
&#xD;
          -  Woman of childbearing potential must agree to follow contraceptive guidance.&#xD;
&#xD;
          -  Capable of giving signed informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Predicted life expectancy &lt;3 months.&#xD;
&#xD;
          -  Primary central nervous system (CNS) tumors.&#xD;
&#xD;
          -  Symptomatic or impending cord compression. Stable CNS disease is allowed.&#xD;
&#xD;
          -  History of cerebrovascular stroke or transient ischemic attack within previous 6&#xD;
             months.&#xD;
&#xD;
          -  Prior solid organ or hematologic transplant.&#xD;
&#xD;
          -  History or current retinal pigment epithelial detachment (RPED), central serous&#xD;
             retinopathy, retinal vascular occlusion (RVO), neovascular macular degeneration.&#xD;
&#xD;
          -  Any clinically significant cardiac disease.&#xD;
&#xD;
          -  Active, known or suspected autoimmune disease.&#xD;
&#xD;
          -  History of or current interstitial lung disease or pneumonitis.&#xD;
&#xD;
          -  Receipt of a live-virus vaccination within 28 days, viral vaccine that do not contain&#xD;
             live virus within 7 days of planned treatment start. Seasonal flu vaccines that do not&#xD;
             contain live virus are permitted.&#xD;
&#xD;
          -  Known infection with human immunodeficiency virus (HIV), known uncontrolled hepatitis&#xD;
             B infection, active tuberculosis, or severe infection requiring parenteral antibiotic&#xD;
             treatment.&#xD;
&#xD;
          -  Inadequate hematologic, hepatic and renal function.&#xD;
&#xD;
          -  Known second malignancy.&#xD;
&#xD;
          -  Impairment of gastrointestinal function.&#xD;
&#xD;
          -  Any unstable or clinically significant concurrent medical condition that would, in the&#xD;
             opinion of the investigator, jeopardize the safety of a participant, impact their&#xD;
             expected survival through the end of the study participation, and/or impact their&#xD;
             ability to comply with the protocol.&#xD;
&#xD;
          -  History of severe allergic reaction to any of the study intervention components.&#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>18 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>University of California Irvine Medical Center-Site Number:8400002</name>
      <address>
        <city>Orange</city>
        <state>California</state>
        <zip>92868</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>~University of Texas - MD Anderson Cancer Center-Site Number:8400001</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :0320001</name>
      <address>
        <city>Caba</city>
        <state>Buenos Aires</state>
        <zip>C1019ABS</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :0320004</name>
      <address>
        <city>Caba</city>
        <state>Ciudad De Buenos Aires</state>
        <zip>C1078AAI</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :0320003</name>
      <address>
        <city>Rosario</city>
        <state>Santa Fe</state>
        <zip>2000</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :0320002</name>
      <address>
        <city>Buenos Aires</city>
        <zip>C1125ABD</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :0360002</name>
      <address>
        <city>Randwick</city>
        <state>New South Wales</state>
        <zip>2031</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :0360001</name>
      <address>
        <city>Woolloongabba</city>
        <state>Queensland</state>
        <zip>4102</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :0360003</name>
      <address>
        <city>Heidelberg West</city>
        <state>Victoria</state>
        <zip>3081</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :1520004</name>
      <address>
        <city>Santiago</city>
        <state>Reg Metropolitana De Santiago</state>
        <zip>7500713</zip>
        <country>Chile</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :1520001</name>
      <address>
        <city>Santiago</city>
        <state>Reg Metropolitana De Santiago</state>
        <zip>8420383</zip>
        <country>Chile</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :1520003</name>
      <address>
        <city>Viña del Mar</city>
        <state>Valparaíso</state>
        <zip>2520598</zip>
        <country>Chile</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :1520002</name>
      <address>
        <city>Temuco</city>
        <zip>4800827</zip>
        <country>Chile</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :4100003</name>
      <address>
        <city>Cheongju-si</city>
        <state>Chungcheongbuk-do</state>
        <zip>28644</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :4100001</name>
      <address>
        <city>Seoul</city>
        <state>Seoul-teukbyeolsi</state>
        <zip>03722</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :4100002</name>
      <address>
        <city>Seongnam-si, Gyeonggi-do</city>
        <zip>13496</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :5280001</name>
      <address>
        <city>Leiden</city>
        <zip>2333 ZA</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :7020001</name>
      <address>
        <city>Singapore</city>
        <country>Singapore</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :7240001</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 :7240002</name>
      <address>
        <city>Madrid / Madrid</city>
        <state>Madrid, Comunidad De</state>
        <zip>28050</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :7240003</name>
      <address>
        <city>Valencia / Valencia</city>
        <state>Valenciana, Comunidad</state>
        <zip>46010</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :1580002</name>
      <address>
        <city>Tainan</city>
        <zip>704</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number :1580001</name>
      <address>
        <city>Taipei</city>
        <zip>100</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Argentina</country>
    <country>Australia</country>
    <country>Chile</country>
    <country>Korea, Republic of</country>
    <country>Netherlands</country>
    <country>Singapore</country>
    <country>Spain</country>
    <country>Taiwan</country>
    <country>United States</country>
  </location_countries>
  <verification_date>May 12, 2023</verification_date>
  <study_first_submitted>May 29, 2020</study_first_submitted>
  <study_first_submitted_qc>June 2, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 5, 2020</study_first_posted>
  <last_update_submitted>May 12, 2023</last_update_submitted>
  <last_update_submitted_qc>May 12, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">May 15, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Neoplasm Metastasis</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pembrolizumab</mesh_term>
    <mesh_term>Adagrasib</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>
  <!-- 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/NCT04418661
org study id: TCD16210
secondary id: U1111-1244-2555
secondary id: 2020-000436-22
nct id: NCT04418661
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
Primary Objectives:

        -  Part 1

        -  To characterize the safety and tolerability of SAR442720 in combination with
           pembrolizumab in participants with advanced solid tumors.

        -  To define the MTD and RP2D for the combination of SAR442720 and pembrolizumab in
           participants with solid tumors.

        -  Part 2

        -  To determine the anti-tumor activity of SAR442720 in combination with pembrolizumab.

        -  Part 3A

        -  To define the MTD and RP2D for the combination of SAR442720 and adagrasib in
           participants with KRAS G12C NSCLC

        -  To characterize the safety and tolerability of SAR442720 in combination with adagrasib
           in participants with KRAS G12C NSCLC

        -  Part 3B

        -  To determine the anti-tumor activity of SAR442720 in combination with adagrasib in
           participants with KRAS G12C NSCLC

        -  Part 4

        -  To evaluate the impact of food on the PK of SAR442720 when dosed with pembrolizumab.

        -  To evaluate the impact of the formulations (formulation 1 and formulation 2) on the PK
           of SAR442720 when dosed with pembrolizumab.

      Secondary Objectives:

        -  Part 1

        -  To assess the PK of SAR442720 with pembrolizumab, and the PK of pembrolizumab with
           SAR442720.

        -  To estimate the anti-tumor effects of SAR442720 with pembrolizumab.

        -  Part 2

        -  To assess the safety profile of SAR442720 combined with pembrolizumab.

        -  To assess other indicators of anti-tumor activity.

        -  To assess the PK of SAR442720 with pembrolizumab, and the PK of pembrolizumab with
           SAR442720.

        -  Part 3A

        -  To characterize the PK of SAR442720 with adagrasib, and the PK of adagrasib with
           SAR442720.

        -  To estimate the anti-tumor effects of SAR442720 with adagrasib

        -  Part 3B

        -  To assess the safety profile of SAR442720 with adagrasib in participants with KRAS G12C
           NSCLC.

        -  To assess other indicators of anti-tumor activity.

        -  To assess the PK of SAR442720 with adagrasib, and the PK of adagrasib with SAR442720.

        -  Part 4

        -  To assess the safety and tolerability of SAR442720 formulations with pembrolizumab

        -  To estimate the anti-tumor effects of SAR442720 with pembrolizumab.
This open label Phase 1 multicenter study is designed to evaluate the safety and maximum
      tolerated dose (MTD) and recommended phase 2 dose (RP2D) of SAR442720 in combination with
      pembrolizumab in participants with solid tumors in Part 1.

      In Part 2, in the expansion cohort (Cohort A) we will assess the antitumor activity and
      safety of SAR442720 combined with pembrolizumab in participants with metastatic 1L lung
      cancer.

      In Part 3, we will evaluate the safety, MTD, RP2D and antitumor activity of SAR442720 in
      combination with adagrasib in participants with lung cancer and KRAS G12C mutation.

      In Part 4, we will evaluate the impact of the formulations (formulation 1 and formulation 2)
      and of the food on the PK of SAR442720 when dosed in combination with pembrolizumab. The
      expected duration of study intervention for participants may vary, based on progression date;
      median expected duration of study per participant is estimated to be about 10 months in Part
      1, Part 3 and Part 4 (up to 1 month for screening, a median of 6 months for treatment, and a
      median of 3 months for long term follow-up) and in Part 2 16 months (up to 1 month for
      screening, a median of 12 months for treatment and a median of 3 months for long term follow
      up.)
allocation: Non-Randomized
intervention model: Sequential Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Incidence of Adverse Events (AEs) SAR442720 and pembrolizumab
time frame: 21 days
description: Part 1:
Incidence, nature, and severity of treatment emergent AEs and serious adverse events (SAEs), graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0 for the combination of SAR442720 and pembrolizumab.
measure: Incidence of study-drug related Dose Limiting Toxicities (DLTs)
time frame: up to 2 years
description: Part 1 and 3A:
Incidence of study drug-related dose-limiting toxicities (DLTs) in Cycle 1.
measure: Objective Response Rate (ORR)
time frame: up to 2 years
description: Part 2 and 3B:
Objective response rate defined as the proportion of participants who have a confirmed CR or partial response (PR) determined by investigator, per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
measure: Incidence of Adverse Events (AEs) SAR442720 and adagrasib
time frame: up to 2 years
description: Part 3A:
Incidence, nature, and severity of TEAEs and SAEs, graded according to NCI CTCAEv5.0 for the combination of SAR442720 and adagrasib.
measure: Part 4: Plasma concentrations of SAR442720 in combination with pembrolizumab under impact of food
time frame: up to 2 years
measure: Part 1 and 2: Plasma concentrations of SAR442720
time frame: up to 2 years
measure: Part 1 and 2: Serum concentration of pembrolizumab
time frame: up to 2 years
measure: Objective response rate (ORR) Part 1 and Part 4
time frame: up to 2 years
description: Part 1 and Part 4:
Objective response rate of SAR442720 and pembrolizumab in all participants. ORR of combination therapy with SAR442720 and pembrolizumab will be based on Response Evaluation Criteria in Solid Tumors (RECIST) v1.
measure: Duration of response (DoR)
time frame: up to 2 years
description: Part 1 and Part 2 and 3B:
Duration of response per RECIST v1.1 is defined as the interval from the first documentation of CR (complete response) or PR (partial response) to the earlier of the first documentation of definitive disease progression or death due to any cause, whichever occurs first.
measure: Incidence of Adverse Events
time frame: up to 2 years
description: Part 2 and 3B and Part 4:
Incidence, nature, and severity of treatment emergent adverse events (TEAEs) and serious adverse events (SAEs) graded according to the NCI CTCAE v5 for the combination of SAR442720 and pembrolizumab.
measure: Time to Response (TTR)
time frame: up to 2 years
description: Part 2 and 3B:
Time to response (TTR) defined as the time from the first administration of investigational medicinal product (IMP) to the first documented evidence of PR or CR determined by the Investigator per RECIST v1.1 (for NSCLC).
measure: Clinical Benefit Rate (CBR)
time frame: up to 2 years
description: Part 2 and 3B:
Clinical benefit rate (CBR) including confirmed CR or PR at any time or stable disease (SD) of at least 6 months (determined by the Investigator per RECIST v1.1.
measure: Disease Control Rate (DCR)
time frame: up to 2 years
description: Part 2 and 3B:
Disease control rate (DCR) including confirmed CR or PR or stable disease (SD) as determined by the Investigator per RECIST v1.1.
measure: Progression free survival (PFS)
time frame: up to 2 years
description: Part 2 and 3B:
Progression free survival (PFS), defined as the time from the date of first IMP administration to the date of the first documented disease progression determined by the Investigator as per RECIST v1.1 or death due to any cause, whichever occurs first.
measure: Part 3A: Plasma concentrations of SAR442720
time frame: up to 2 years
measure: Part 3A: Plasma concentrations of adagrasib
time frame: up to 2 years
measure: Objective Response Rate (ORR) of SAR442720 and adagrasib
time frame: up to 2 years
description: Part 3A:
ORR of SAR442720 and adagrasib in all participants. ORR of combination therapy with SAR442720 and adagrasib will be based on RECIST v1.1.
measure: Duration of Response (DOR) of SAR442720 and adagrasib
time frame: up to 2 years
description: Part 3:
DOR of SAR442720 and adagrasib in all participants. ORR of combination therapy with SAR442720 and adagrasib will be based on RECIST v1.1.
measure: Part 3B: Plasma concentrations of SAR442720 and adagrasib
time frame: up to 2 years
arm group label: SAR442720 + Pembrolizumab
arm group type: Experimental
description: Part 1:
SAR442720 (also known as RMC-4630) will be administered orally twice a week (BIW) followed by pembrolizumab which is given intravenously (IV) once every 3 weeks (Q3W). The dose of SAR442720 will be escalated or de-escalated depending on the emerging safety data of the combination.
arm group label: SAR442720 + Pembrolizumab: Non-small cell lung cancer with Tumor proportion score > 50%
arm group type: Experimental
description: Part 2:
SAR442720 dose will be administered orally in combination with Pembrolizumab which is given by IV infusion once every 3 weeks (Q3W) or once every 6 weeks (Q6W)
arm group label: SAR442720 + Pembrolizumab: Non-small cell lung cancer with Tumor proportion score 1-49%
arm group type: Experimental
description: Part 2:
SAR442720 dose will be administered orally in combination with Pembrolizumab which is given by IV infusion once every 3 weeks (Q3W) or once every 6 weeks (Q6W)
arm group label: SAR444270 + adagrasib: Dose Escalation
arm group type: Experimental
description: Part 3A; SAR442720 and adagrasib will be administered orally on a continuous basis.
arm group label: SAR444270 + adagrasib: Dose Expansion
arm group type: Experimental
description: Part 3B:
Once SAR442720 dose is confirmed in Part 3A SAR442720 and adagrasib will be administered orally on a continuous basis.
arm group label: SAR442720 + Pembrolizumab continuous
arm group type: Experimental
description: Part 4:
SAR442720 will be administered orally in combination with Pembrolizumab which is given by IV infusion once every 3 weeks (Q3W) or once every 6 weeks (Q6W)
intervention type: Drug
intervention name: SAR442720
description: Pharmaceutical form: Varies Route of administration: Varies
arm group label: SAR442720 + Pembrolizumab
arm group label: SAR442720 + Pembrolizumab continuous
arm group label: SAR442720 + Pembrolizumab: Non-small cell lung cancer with Tumor proportion score 1-49%
arm group label: SAR442720 + Pembrolizumab: Non-small cell lung cancer with Tumor proportion score > 50%
arm group label: SAR444270 + adagrasib: Dose Escalation
arm group label: SAR444270 + adagrasib: Dose Expansion
intervention type: Drug
intervention name: Pembrolizumab
description: Pharmaceutical form:Sterile Lyophilized powder for reconstitution Route of administration: Infusion
arm group label: SAR442720 + Pembrolizumab
arm group label: SAR442720 + Pembrolizumab continuous
arm group label: SAR442720 + Pembrolizumab: Non-small cell lung cancer with Tumor proportion score 1-49%
arm group label: SAR442720 + Pembrolizumab: Non-small cell lung cancer with Tumor proportion score > 50%
intervention type: Drug
intervention name: Adagrasib
description: Pharmaceutical form:Sterile Tablet Route of administration: Oral
arm group label: SAR444270 + adagrasib: Dose Escalation
arm group label: SAR444270 + adagrasib: Dose Expansion
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Clinical Sciences & Operations
role: Study Director
affiliation: Sanofi
facility: 
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country: Argentina
country: Australia
country: Chile
country: Korea, Republic of
country: Netherlands
country: Singapore
country: Spain
country: Taiwan
country: United States
responsible party type: Sponsor
mesh term: Neoplasm Metastasis
mesh term: Pembrolizumab
mesh term: Adagrasib
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