<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/NCT03829436</url>
  </required_header>
  <id_info>
    <org_study_id>TPST-1120-001</org_study_id>
    <nct_id>NCT03829436</nct_id>
  </id_info>
  <brief_title>TPST-1120 as Monotherapy and in Combination With Nivolumab in Subjects With Advanced Cancers</brief_title>
  <official_title>A Phase 1/1b Open-label, Dose-escalation and Dose-expansion Study of TPST-1120 as a Single Agent or in Combination With Systemic Anti-Cancer Therapies in Subjects With Advanced Solid Tumors</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Tempest Therapeutics</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Tempest Therapeutics</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 is a phase 1/1b open label, multicenter dose escalation and dose expansion study to&#xD;
      investigate the safety, tolerability and anti-tumor activity of TPST-1120, a small molecule&#xD;
      selective antagonist of PPARα (peroxisome proliferator activated receptor alpha) as&#xD;
      monotherapy and in combination with a systemic anticancer agent, nivolumab, an anti-PD1&#xD;
      antibody, in subjects with advanced solid tumors.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a phase 1/1b open label, multicenter, dose escalation and dose expansion study to&#xD;
      evaluate the safety, tolerability, PK, pharmacodynamics, and preliminary antitumor activity&#xD;
      of TPST-1120, a small molecule selective antagonist of PPARα (peroxisome proliferator&#xD;
      activated receptor alpha) in adult subjects with selected advanced solid tumors. TPST-1120&#xD;
      will be administered as monotherapy and in combination with a systemic anticancer agent,&#xD;
      nivolumab, an anti-PD1 antibody, in subjects with advanced solid tumors. This trial is&#xD;
      composed of dose escalation and dose expansion cohorts.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">March 20, 2019</start_date>
  <completion_date type="Actual">September 7, 2022</completion_date>
  <primary_completion_date type="Actual">September 7, 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>Sequential Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Incidence of dose limiting toxicities (DLTs) of TPST-1120 as a single agent and in combination with nivolumab.</measure>
    <time_frame>From start of treatment to end of treatment, up to 36 months</time_frame>
    <description>Incidence of dose limiting toxicities (DLTs) of TPST-1120 as a single agent and in combination with nivolumab.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidence of treatment-emergent adverse events as assessed by NCI-CTCAE v5.0 of TPST-1120 as a single agent and in combination with nivolumab.</measure>
    <time_frame>From start of treatment to end of treatment, up to 36 months</time_frame>
    <description>Incidence of treatment-emergent adverse events as assessed by NCI-CTCAE v5.0 of TPST-1120 as a single agent and in combination with nivolumab.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Identify the maximum tolerated dose</measure>
    <time_frame>From start of treatment to end of treatment, up to 36 months</time_frame>
    <description>Incidence of dose limiting toxicities (DLTs) of TPST-1120 as a single agent and in combination with nivolumab.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Assess pharmacokinetics: Maximum serum concentration (Cmax)</measure>
    <time_frame>Day 1, 2, 8 of Cycle 1 and Day 1 of Cycle 3 (cycle can be 21 or 28 days, depending on cohort assignment)</time_frame>
    <description>Maximum serum concentration (Cmax) of TPST-1120</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assess pharmacokinetics: Area under the curve (AUC)</measure>
    <time_frame>Day 1, 2, 8 of Cycle 1 and Day 1 of Cycle 3, Day 1 of Cycles 5+ (cycle can be 21 or 28 days, depending on cohort assignment)</time_frame>
    <description>Area under the curve (AUC) of TPST-1120</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Objective response rate</measure>
    <time_frame>From start of treatment to end of treatment, up to 36 months</time_frame>
    <description>Objective response rate per RECIST v1.1 criterion of TPST-1120 as a single agent and in combination with nivolumab.</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">38</enrollment>
  <condition>Hepatocellular Carcinoma</condition>
  <condition>Metastatic Castration Resistant Prostate Cancer</condition>
  <condition>Renal Cell Carcinoma</condition>
  <condition>Non-small Cell Lung Cancer</condition>
  <condition>Colorectal Cancer</condition>
  <condition>Squamous Cell Carcinoma of Head and Neck</condition>
  <condition>Triple-Negative Breast Cancer</condition>
  <condition>Urothelial Carcinoma</condition>
  <condition>Cholangiocarcinoma</condition>
  <condition>GastroEsophageal Cancer</condition>
  <condition>Pancreatic Cancer</condition>
  <condition>Sarcoma</condition>
  <arm_group>
    <arm_group_label>Part 1 TPST-1120</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects will receive escalating doses of TPST-1120 administered orally twice daily continuously until MTD is reached or until disease progression</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 2 TPST-1120 + nivolumab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects will receive escalating doses of TPST-1120 administered orally twice daily in combination with nivolumab administered intravenously every 28 days until MTD is reached for TPST-1120 or until disease progression.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 3 TPST-1120</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Selected dose of TPST-1120 administered orally twice daily until disease progression</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 4 TPST-1120 + nivolumab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Selected dose of TPST-1120 administered orally twice daily in combination with nivolumab administered intravenously every 28 days until MTD is reached for TPST-1120 or until disease progression</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Part 1 TPST-1120</intervention_name>
    <description>Subjects will receive escalating doses of TPST-1120 administered orally twice daily continuously until MTD is reached or until disease progression</description>
    <arm_group_label>Part 1 TPST-1120</arm_group_label>
    <other_name>Experimental</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Part 2 TPST-1120 + nivolumab</intervention_name>
    <description>Subjects will receive escalating doses of TPST-1120 administered orally twice daily</description>
    <arm_group_label>Part 2 TPST-1120 + nivolumab</arm_group_label>
    <other_name>Experimental + Opdivo</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Part 3 TPST-1120</intervention_name>
    <description>Selected dose of TPST-1120 administered orally twice daily until disease progression</description>
    <arm_group_label>Part 3 TPST-1120</arm_group_label>
    <other_name>Experimental</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Part 4 TPST-1120 + nivolumab</intervention_name>
    <description>Selected dose of TPST-1120 administered orally twice daily in combination with nivolumab administered intravenously every 28 days until MTD is reached for TPST-1120 or until disease progression</description>
    <arm_group_label>Part 4 TPST-1120 + nivolumab</arm_group_label>
    <other_name>Experimental + Opdivo</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group performance status of 0-1 at enrollment&#xD;
&#xD;
          -  Progressive disease or previously untreated tumors for which no standard therapy&#xD;
             exists or treatment naïve at the time of study entry are eligible&#xD;
&#xD;
          -  Have at least one measurable lesion according to RECIST v1.1&#xD;
&#xD;
          -  Subjects with the following histologies are eligible and who are refractory to, have&#xD;
             failed, are intolerant to, are ineligible for standard therapy, or for which no&#xD;
             standard therapy exists are eligible: Part 1 (Dose Escalation- Monotherapy): RCC,&#xD;
             NSCLC, CRC, metastatic castration resistant prostate cancer (mCRPC),&#xD;
             cholangiocarcinoma, TNBC, pancreatic cancer, HCC, gastroesophageal cancer, squamous&#xD;
             cell carcinoma of head and neck (SCCHN), urothelial bladder cancer (UBC), and sarcoma&#xD;
             (liposarcomas and leiomyosarcomas); Part 2 (Dose Escalation-Combination with&#xD;
             nivolumab): RCC, HCC, and cholangiocarcinoma; Part 3 (Dose Expansion-Monotherapy):&#xD;
             RCC, HCC and cholangiocarcinoma; Part 4 (Dose Expansion-Combination with nivolumab):&#xD;
             HCC.&#xD;
&#xD;
        Exclusion Criteria&#xD;
&#xD;
          -  Concurrent enrollment in another clinical study, unless it is an observational&#xD;
             (non-interventional) clinical study, a specimen-collection study or the follow-up&#xD;
             period of an interventional study&#xD;
&#xD;
          -  Any chemotherapy, monoclonal antibody therapy, radiotherapy, investigational,&#xD;
             biologic, or hormonal therapy for cancer treatment within 28 days of commencing&#xD;
             TPST-1120 treatment. Targeted therapy such as tyrosine kinase inhibitors within 14&#xD;
             days of commencing first dose of study drug(s)&#xD;
&#xD;
          -  For subjects who have received prior anti-PD-1, anti-PD-L1, or anti-CTLA4 therapy:&#xD;
&#xD;
               1. Subjects must not have experienced an irAE toxicity that led to permanent&#xD;
                  discontinuation of prior immunotherapy.&#xD;
&#xD;
               2. Any unresolved irAE &gt; Grade 1 with prior immunotherapy treatment.&#xD;
&#xD;
          -  Symptomatic, untreated or actively progressing central nervous system metastases&#xD;
&#xD;
          -  Have received fibrates within 28 days before first dose of investigational agent&#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>Robert Stagg, PharmD</last_name>
    <role>Study Director</role>
    <affiliation>Tempest Therapeutics</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of California - San Francisco</name>
      <address>
        <city>San Francisco</city>
        <state>California</state>
        <zip>94158</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Miami Cancer Institute</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33176</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Johns Hopkins University</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21287</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Michigan Rogel Cancer Center</name>
      <address>
        <city>Ann Arbor</city>
        <state>Michigan</state>
        <zip>48109</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Columbia University Medical Center</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10024</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Carolina BioOncology Institute</name>
      <address>
        <city>Huntersville</city>
        <state>North Carolina</state>
        <zip>28078</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Stephenson Cancer Center</name>
      <address>
        <city>Oklahoma City</city>
        <state>Oklahoma</state>
        <zip>73104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Pennsylvania Perelman School of Medicine</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Thomas Jefferson University Hospital</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19107</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UPMC Hillman Cancer Center</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <zip>15213</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sarah Cannon Research Institute - TN</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37203</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>June 2023</verification_date>
  <study_first_submitted>January 30, 2019</study_first_submitted>
  <study_first_submitted_qc>February 1, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 4, 2019</study_first_posted>
  <last_update_submitted>June 28, 2023</last_update_submitted>
  <last_update_submitted_qc>June 28, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">July 3, 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>Carcinoma</mesh_term>
    <mesh_term>Carcinoma, Renal Cell</mesh_term>
    <mesh_term>Triple Negative Breast Neoplasms</mesh_term>
    <mesh_term>Cholangiocarcinoma</mesh_term>
    <mesh_term>Squamous Cell Carcinoma of Head and Neck</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Nivolumab</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/NCT03829436
org study id: TPST-1120-001
nct id: NCT03829436
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
This is a phase 1/1b open label, multicenter dose escalation and dose expansion study to
      investigate the safety, tolerability and anti-tumor activity of TPST-1120, a small molecule
      selective antagonist of PPARα (peroxisome proliferator activated receptor alpha) as
      monotherapy and in combination with a systemic anticancer agent, nivolumab, an anti-PD1
      antibody, in subjects with advanced solid tumors.
This is a phase 1/1b open label, multicenter, dose escalation and dose expansion study to
      evaluate the safety, tolerability, PK, pharmacodynamics, and preliminary antitumor activity
      of TPST-1120, a small molecule selective antagonist of PPARα (peroxisome proliferator
      activated receptor alpha) in adult subjects with selected advanced solid tumors. TPST-1120
      will be administered as monotherapy and in combination with a systemic anticancer agent,
      nivolumab, an anti-PD1 antibody, in subjects with advanced solid tumors. This trial is
      composed of dose escalation and dose expansion cohorts.
allocation: Non-Randomized
intervention model: Sequential Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Incidence of dose limiting toxicities (DLTs) of TPST-1120 as a single agent and in combination with nivolumab.
time frame: From start of treatment to end of treatment, up to 36 months
description: Incidence of dose limiting toxicities (DLTs) of TPST-1120 as a single agent and in combination with nivolumab.
measure: Incidence of treatment-emergent adverse events as assessed by NCI-CTCAE v5.0 of TPST-1120 as a single agent and in combination with nivolumab.
time frame: From start of treatment to end of treatment, up to 36 months
description: Incidence of treatment-emergent adverse events as assessed by NCI-CTCAE v5.0 of TPST-1120 as a single agent and in combination with nivolumab.
measure: Identify the maximum tolerated dose
time frame: From start of treatment to end of treatment, up to 36 months
description: Incidence of dose limiting toxicities (DLTs) of TPST-1120 as a single agent and in combination with nivolumab.
measure: Assess pharmacokinetics: Maximum serum concentration (Cmax)
time frame: Day 1, 2, 8 of Cycle 1 and Day 1 of Cycle 3 (cycle can be 21 or 28 days, depending on cohort assignment)
description: Maximum serum concentration (Cmax) of TPST-1120
measure: Assess pharmacokinetics: Area under the curve (AUC)
time frame: Day 1, 2, 8 of Cycle 1 and Day 1 of Cycle 3, Day 1 of Cycles 5+ (cycle can be 21 or 28 days, depending on cohort assignment)
description: Area under the curve (AUC) of TPST-1120
measure: Objective response rate
time frame: From start of treatment to end of treatment, up to 36 months
description: Objective response rate per RECIST v1.1 criterion of TPST-1120 as a single agent and in combination with nivolumab.
arm group label: Part 1 TPST-1120
arm group type: Experimental
description: Subjects will receive escalating doses of TPST-1120 administered orally twice daily continuously until MTD is reached or until disease progression
arm group label: Part 2 TPST-1120 + nivolumab
arm group type: Experimental
description: Subjects will receive escalating doses of TPST-1120 administered orally twice daily in combination with nivolumab administered intravenously every 28 days until MTD is reached for TPST-1120 or until disease progression.
arm group label: Part 3 TPST-1120
arm group type: Experimental
description: Selected dose of TPST-1120 administered orally twice daily until disease progression
arm group label: Part 4 TPST-1120 + nivolumab
arm group type: Experimental
description: Selected dose of TPST-1120 administered orally twice daily in combination with nivolumab administered intravenously every 28 days until MTD is reached for TPST-1120 or until disease progression
intervention type: Drug
intervention name: Part 1 TPST-1120
description: Subjects will receive escalating doses of TPST-1120 administered orally twice daily continuously until MTD is reached or until disease progression
arm group label: Part 1 TPST-1120
other name: Experimental
intervention type: Drug
intervention name: Part 2 TPST-1120 + nivolumab
description: Subjects will receive escalating doses of TPST-1120 administered orally twice daily
arm group label: Part 2 TPST-1120 + nivolumab
other name: Experimental + Opdivo
intervention type: Drug
intervention name: Part 3 TPST-1120
description: Selected dose of TPST-1120 administered orally twice daily until disease progression
arm group label: Part 3 TPST-1120
other name: Experimental
intervention type: Drug
intervention name: Part 4 TPST-1120 + nivolumab
description: Selected dose of TPST-1120 administered orally twice daily in combination with nivolumab administered intravenously every 28 days until MTD is reached for TPST-1120 or until disease progression
arm group label: Part 4 TPST-1120 + nivolumab
other name: Experimental + Opdivo
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Robert Stagg, PharmD
role: Study Director
affiliation: Tempest Therapeutics
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Carcinoma
mesh term: Carcinoma, Renal Cell
mesh term: Triple Negative Breast Neoplasms
mesh term: Cholangiocarcinoma
mesh term: Squamous Cell Carcinoma of Head and Neck
mesh term: Nivolumab
sharing ipd: No