<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/NCT03301896</url>
  </required_header>
  <id_info>
    <org_study_id>CLHC165X2101</org_study_id>
    <nct_id>NCT03301896</nct_id>
  </id_info>
  <brief_title>Study of the Safety and Efficacy of LHC165 Single Agent and in Combination With PDR001 in Patients With Advanced Malignancies</brief_title>
  <official_title>A Phase I/Ib, Open-label, Multi-center Dose-escalation and Dose-expansion Study of the Safety and Tolerability of Intra-tumorally Administered LHC165 Single Agent and in Combination With PDR001 in Patients With Advanced Malignancies</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Novartis Pharmaceuticals</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Novartis</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>
      The purpose of this trial was to explore the clinical utility of two investigational agents&#xD;
      in patients with advanced cancer.&#xD;
&#xD;
      This was a multi-center, open-label Phase I/Ib study. The primary objectives of the trial&#xD;
      were:&#xD;
&#xD;
        -  To characterize the safety and tolerability of intratumoral LHC165 in patients with&#xD;
           solid tumors as a single agent and in combination with PDR001&#xD;
&#xD;
        -  To determine and evaluate the maximum tolerated dose (MTD)/recommended dose (RD) for&#xD;
           LHC165 as a single agent and in combination with PDR001&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This was a multi-center, open-label Phase I/Ib study. The study consisted of four dose&#xD;
      escalation parts and two dose expansion parts testing LHC165 as a single agent or LHC165 in&#xD;
      combination with PDR001. The dose escalation parts estimated the Maximum Tolerated Dose (MTD)&#xD;
      and/or Recommended Dose for Expansion (RDE) and were planned to test two different dosing&#xD;
      schedules for LHC165 single agent (Group A and B) and LHC165 in combination with PDR001&#xD;
      (Group C and D).&#xD;
&#xD;
      The dose expansion parts of the study were planned to use the MTD/RDE for each the LHC165&#xD;
      single agent (Group E) and LHC165 in combination with PDR001 (Group F), determined in the&#xD;
      respective dose escalation parts to assess the activity, safety and tolerability of LHC165 as&#xD;
      a single agent or LHC165 in combination with PDR001 in patients with specific types of solid&#xD;
      tumors.&#xD;
&#xD;
      The study was terminated due to business reasons. Groups B, D and E were not opened for&#xD;
      enrollment.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Business reasons&#xD;
  </why_stopped>
  <start_date type="Actual">January 31, 2018</start_date>
  <completion_date type="Actual">June 30, 2022</completion_date>
  <primary_completion_date type="Actual">June 30, 2022</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>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Escalation: Incidence of Dose-limiting Toxicities (DLTs) in Cycle 1</measure>
    <time_frame>day 28</time_frame>
    <description>Dose Limiting Toxicity Evaluation Period</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Escalation and Expansion: Incidence and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs), including changes in laboratory parameters, vital signs, electrocardiograms (ECGs)</measure>
    <time_frame>24 months</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Objective Response Rate (ORR) per RECIST 1.1 and iRECIST</measure>
    <time_frame>24 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Best Overall Response (BOR) per RECIST 1.1 and iRECIST</measure>
    <time_frame>24 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression-Free Survival (PFS) per RECIST 1.1 and iRECIST</measure>
    <time_frame>24 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of Response (DOR) per RECIST 1.1 and iRECIST</measure>
    <time_frame>24 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Disease Control Rate (DCR) per RECIST 1.1 and iRECIST</measure>
    <time_frame>24 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Serum concentration profiles of LHC165 as a single agent: Cmax</measure>
    <time_frame>24 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Serum concentration profiles of LHC165 in combination with PDR001 and derived PK parameters: Cmax</measure>
    <time_frame>24 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Serum concentration profiles of PDR001 in combination with LHC165 and derived PK parameters: Cmax</measure>
    <time_frame>24 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Serum concentration profiles of LHC165 as a single agent: AUC</measure>
    <time_frame>24 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Serum concentration profiles of LHC165 in combination with PDR001 and derived PK parameters: AUC</measure>
    <time_frame>24 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Serum concentration profiles of PDR001 in combination with LHC165 and derived PK parameters: AUC</measure>
    <time_frame>24 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Serum concentration profiles of LHC165 as a single agent: Tmax</measure>
    <time_frame>24 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Serum concentration profiles of LHC165 in combination with PDR001 and derived PK parameters: Tmax</measure>
    <time_frame>24 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Serum concentration profiles of PDR001 in combination with LHC165 and derived PK parameters: Tmax</measure>
    <time_frame>24 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Presence and titer of anti-PDR001 antibodies</measure>
    <time_frame>24 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in tumor infiltrating lymphocytes in injected and distal tumor specimens</measure>
    <time_frame>24 months</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">45</enrollment>
  <condition>Solid Tumors</condition>
  <arm_group>
    <arm_group_label>LHC165 single agent</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>LHC165 intratumoral injection given alone</description>
  </arm_group>
  <arm_group>
    <arm_group_label>LHC165 in combination with PDR001</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>LHC165 intratumoral injection given with PDR001 infusion</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>LHC165</intervention_name>
    <description>LHC165 intratumoral injection</description>
    <arm_group_label>LHC165 in combination with PDR001</arm_group_label>
    <arm_group_label>LHC165 single agent</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>PDR001</intervention_name>
    <description>PDR001 infusion</description>
    <arm_group_label>LHC165 in combination with PDR001</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Written informed consent must be obtained prior to any procedures unless considered&#xD;
             standard of care.&#xD;
&#xD;
          -  Adult men and women (≥ 18 years of age) with histologically confirmed diagnosis of&#xD;
             metastatic and/or advanced solid tumors not amenable to curative treatment by surgery.&#xD;
&#xD;
          -  Patients must be willing and able to comply with the protocol for the duration of the&#xD;
             study including undergoing treatment and scheduled visits and examinations including&#xD;
             follow up.&#xD;
&#xD;
          -  Dose escalation: Patients with accessible tumors and with measurable disease as&#xD;
             determined by RECIST 1.1 and have progressed despite standard treatment or are&#xD;
             intolerant of standard treatment, or for whom no standard treatment exists.&#xD;
&#xD;
          -  Dose expansion: Patients with advanced/metastatic solid tumors: HNSCC, melanoma,&#xD;
             accessible tumors and visceral tumors (LHC165 combination with PDR001 only). Patients&#xD;
             must have measurable disease as determined by RECIST 1.1 and have progressed despite&#xD;
             standard treatment or are intolerant to standard treatment, or for whom no standard&#xD;
             treatment exists• Patients must have at least two sites of disease amenable to biopsy.&#xD;
&#xD;
          -  Patient has an Eastern Cooperative Oncology Group (ECOG) performance status 0-2.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Presence of symptomatic or uncontrolled central nervous system (CNS) metastases&#xD;
             requiring local CNS-directed treatment.&#xD;
&#xD;
          -  Patients diagnosed with hematological malignancies.&#xD;
&#xD;
          -  Patients with prior stem cell transplants.&#xD;
&#xD;
          -  Patients previously treated with TLR-7/8 agonist treatment.&#xD;
&#xD;
          -  History of primary immunodeficiency&#xD;
&#xD;
          -  Patients who discontinued prior anti-PD-1/PD-L1 therapy due to an&#xD;
             anti-PD-1/PD-L1-related toxicity.&#xD;
&#xD;
          -  Malignant disease, other than that being treated in this study&#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>Nehal Parikh, MD</last_name>
    <role>Study Director</role>
    <affiliation>Novartis Pharmaceuticals</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>UCLA</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90095</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>Novartis Investigative Site</name>
      <address>
        <city>Wilrijk</city>
        <zip>2610</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Ulm</city>
        <zip>89081</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Milano</city>
        <state>MI</state>
        <zip>20141</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Chuo ku</city>
        <state>Tokyo</state>
        <zip>104 0045</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Seoul</city>
        <zip>03080</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Barcelona</city>
        <state>Catalunya</state>
        <zip>08035</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Madrid</city>
        <zip>28009</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Belgium</country>
    <country>Germany</country>
    <country>Italy</country>
    <country>Japan</country>
    <country>Korea, Republic of</country>
    <country>Spain</country>
    <country>United States</country>
  </location_countries>
  <removed_countries>
    <country>Canada</country>
    <country>France</country>
  </removed_countries>
  <link>
    <url>https://www.novctrd.com/ctrdweb/trialresult/trialresults/pdf?trialResultId=18030</url>
    <description>Study Results</description>
  </link>
  <verification_date>April 2023</verification_date>
  <study_first_submitted>September 29, 2017</study_first_submitted>
  <study_first_submitted_qc>September 29, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">October 4, 2017</study_first_posted>
  <last_update_submitted>April 5, 2023</last_update_submitted>
  <last_update_submitted_qc>April 5, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">April 7, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Phase I</keyword>
  <keyword>LHC165</keyword>
  <keyword>PDR001</keyword>
  <keyword>intratumoral injection</keyword>
  <keyword>abscopal</keyword>
  <keyword>checkpoint inhibitor</keyword>
  <keyword>programmed cell death</keyword>
  <keyword>PD-1</keyword>
  <keyword>TLR-7</keyword>
  <keyword>toll-like receptor</keyword>
  <keyword>melanoma</keyword>
  <keyword>head and neck</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Spartalizumab</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </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/NCT03301896
org study id: CLHC165X2101
nct id: NCT03301896
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
The purpose of this trial was to explore the clinical utility of two investigational agents
      in patients with advanced cancer.

      This was a multi-center, open-label Phase I/Ib study. The primary objectives of the trial
      were:

        -  To characterize the safety and tolerability of intratumoral LHC165 in patients with
           solid tumors as a single agent and in combination with PDR001

        -  To determine and evaluate the maximum tolerated dose (MTD)/recommended dose (RD) for
           LHC165 as a single agent and in combination with PDR001
This was a multi-center, open-label Phase I/Ib study. The study consisted of four dose
      escalation parts and two dose expansion parts testing LHC165 as a single agent or LHC165 in
      combination with PDR001. The dose escalation parts estimated the Maximum Tolerated Dose (MTD)
      and/or Recommended Dose for Expansion (RDE) and were planned to test two different dosing
      schedules for LHC165 single agent (Group A and B) and LHC165 in combination with PDR001
      (Group C and D).

      The dose expansion parts of the study were planned to use the MTD/RDE for each the LHC165
      single agent (Group E) and LHC165 in combination with PDR001 (Group F), determined in the
      respective dose escalation parts to assess the activity, safety and tolerability of LHC165 as
      a single agent or LHC165 in combination with PDR001 in patients with specific types of solid
      tumors.

      The study was terminated due to business reasons. Groups B, D and E were not opened for
      enrollment.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Escalation: Incidence of Dose-limiting Toxicities (DLTs) in Cycle 1
time frame: day 28
description: Dose Limiting Toxicity Evaluation Period
measure: Escalation and Expansion: Incidence and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs), including changes in laboratory parameters, vital signs, electrocardiograms (ECGs)
time frame: 24 months
measure: Objective Response Rate (ORR) per RECIST 1.1 and iRECIST
time frame: 24 months
measure: Best Overall Response (BOR) per RECIST 1.1 and iRECIST
time frame: 24 months
measure: Progression-Free Survival (PFS) per RECIST 1.1 and iRECIST
time frame: 24 months
measure: Duration of Response (DOR) per RECIST 1.1 and iRECIST
time frame: 24 months
measure: Disease Control Rate (DCR) per RECIST 1.1 and iRECIST
time frame: 24 months
measure: Serum concentration profiles of LHC165 as a single agent: Cmax
time frame: 24 months
measure: Serum concentration profiles of LHC165 in combination with PDR001 and derived PK parameters: Cmax
time frame: 24 months
measure: Serum concentration profiles of PDR001 in combination with LHC165 and derived PK parameters: Cmax
time frame: 24 months
measure: Serum concentration profiles of LHC165 as a single agent: AUC
time frame: 24 months
measure: Serum concentration profiles of LHC165 in combination with PDR001 and derived PK parameters: AUC
time frame: 24 months
measure: Serum concentration profiles of PDR001 in combination with LHC165 and derived PK parameters: AUC
time frame: 24 months
measure: Serum concentration profiles of LHC165 as a single agent: Tmax
time frame: 24 months
measure: Serum concentration profiles of LHC165 in combination with PDR001 and derived PK parameters: Tmax
time frame: 24 months
measure: Serum concentration profiles of PDR001 in combination with LHC165 and derived PK parameters: Tmax
time frame: 24 months
measure: Presence and titer of anti-PDR001 antibodies
time frame: 24 months
measure: Change from baseline in tumor infiltrating lymphocytes in injected and distal tumor specimens
time frame: 24 months
arm group label: LHC165 single agent
arm group type: Experimental
description: LHC165 intratumoral injection given alone
arm group label: LHC165 in combination with PDR001
arm group type: Experimental
description: LHC165 intratumoral injection given with PDR001 infusion
intervention type: Drug
intervention name: LHC165
description: LHC165 intratumoral injection
arm group label: LHC165 in combination with PDR001
arm group label: LHC165 single agent
intervention type: Biological
intervention name: PDR001
description: PDR001 infusion
arm group label: LHC165 in combination with PDR001
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Nehal Parikh, MD
role: Study Director
affiliation: Novartis Pharmaceuticals
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Belgium
country: Germany
country: Italy
country: Japan
country: Korea, Republic of
country: Spain
country: United States
country: Canada
country: France
url: https://www.novctrd.com/ctrdweb/trialresult/trialresults/pdf?trialResultId=18030
description: Study Results
responsible party type: Sponsor
mesh term: Neoplasms
mesh term: Spartalizumab
sharing ipd: No