<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/NCT04485013</url>
  </required_header>
  <id_info>
    <org_study_id>TTX-080-001</org_study_id>
    <nct_id>NCT04485013</nct_id>
  </id_info>
  <brief_title>TTX-080 HLA-G Antagonist in Subjects With Advanced Cancers</brief_title>
  <official_title>A Phase 1a/1b Dose Escalation/Expansion Study of TTX-080, an HLA-G Antagonist, as Monotherapy and in Combination With Pembrolizumab or Cetuximab in Patients With Advanced Solid Refractory/Resistant Malignancies</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Tizona Therapeutics, Inc</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Tizona 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>
      TTX-080-001 is a Phase 1, open label, dose escalation and dose expansion clinical study to&#xD;
      determine the safety, tolerability, and recommended Phase 2 dose of TTX-080 monotherapy&#xD;
      (HLA-G inhibitor) and in combination with either pembrolizumab (PD-1 inhibitor) or cetuximab&#xD;
      (EGFR inhibitor) in patients with advanced refractory / resistant solid malignancies.&#xD;
&#xD;
      The study is enrolling in the dose expansion arms.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      TTX-080 is a fully human mAb designed to block the interaction of HLA-G with its known&#xD;
      ligands, ILT2 and ILT4 molecules. The Phase 1a was an open label, multicenter, dose&#xD;
      escalation clinical trial to determine the safety, tolerability, MTD or OBD and the RP2D of&#xD;
      TTX-080 when administered as a single agent. The Phase 1b is a dose expansion of TTX-080&#xD;
      monotherapy and in combination with either pembrolizumab or cetuximab in adult subjects with&#xD;
      advanced refractory/resistant solid malignancies, including Head and Neck squamous cell&#xD;
      carcinoma (HNSCC), Non-Small Cell Lung Cancer (NSCLC), Colorectal cancer (CRC), triple&#xD;
      negative breast cancer (TNBC), renal cell carcinoma (RCC), and acral melanoma. Additionally,&#xD;
      the study will seek to evaluate the pharmacokinetics and immunogenicity of TTX-080, and&#xD;
      preliminary efficacy of TTX-080 as a monotherapy and in combination with pembrolizumab or&#xD;
      cetuximab.&#xD;
&#xD;
      The study is enrolling in the dose expansion cohorts.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">July 14, 2020</start_date>
  <completion_date type="Anticipated">June 1, 2024</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2023</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>1. To determine the anti-tumor activity of TTX-080 by objective response rate [complete response + partial response) for each tumor arm per RECIST 1.1</measure>
    <time_frame>Up to 48 months</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Duration of Response, Progression Free Survival per RECIST 1.1</measure>
    <time_frame>Up to 48 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival</measure>
    <time_frame>Up to 48 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adverse events (AEs) as characterized by the incidence, type, frequency, severity (graded according to NCI-CTCAE v5.0), timing, seriousness, and relationship to investigational product, and/or combination therapy, and/or individual approved therapies</measure>
    <time_frame>Up to 48 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Tolerability: The number of cycles of TTX-080 received by patients before discontinuing due to unmanageable drug reactions</measure>
    <time_frame>Up to 48 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Serum levels of Anti Drug Antibody against TTX-080</measure>
    <time_frame>Up to 48 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cmax: Maximum Observed Plasma Concentration for TTX-080</measure>
    <time_frame>Up to 48 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Tmax: Time to Reach the Cmax for TTX-080</measure>
    <time_frame>Up to 48 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUC(0-t): Area Under the Plasma Concentration-time Curve From Zero Time to the Last Measurable Point for TTX-080</measure>
    <time_frame>Up to 48 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUC(0-Inf): Area Under the Plasma Concentration-time Curve From Zero to Infinity for TTX-080</measure>
    <time_frame>Up to 48 months</time_frame>
  </secondary_outcome>
  <number_of_arms>9</number_of_arms>
  <enrollment type="Anticipated">240</enrollment>
  <condition>Cancer</condition>
  <arm_group>
    <arm_group_label>Phase 1a, Monotherapy Dose Escalation</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Phase 1b, Dose Expansion: TTX-080 in combination with pembrolizumab (HNSCC)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Arm 1 will enroll subjects with advanced/metastatic, prior checkpoint inhibitor treated Head and Neck Squamous Cell Carcinoma (HNSCC)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Phase 1b, Dose Expansion: TTX-080 in combination with cetuximab (HNSCC)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Arm 2 will enroll subjects with advanced/metastatic Head and Neck Squamous Cell Carcinoma (HNSCC)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Phase 1b, Dose Expansion: TTX-080 monotherapy (CRC)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Arm 3 will enroll subjects with advanced/metastatic colorectal cancer (CRC)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Phase 1b, Dose Expansion: TTX-080 in combination with cetuximab (CRC), prior anti-EGFR therapy</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Arm 4 will enroll subjects with advanced/metastatic MSI-L/MSS, KRAS wild-type colorectal cancer (CRC) who have progressed on a prior anti-EGFR therapy</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Phase 1b, Dose Expansion: TTX-080 in combination with cetuximab (CRC), no prior anti-EGFR therapy</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Arm 5 will enroll subjects with advanced/metastatic MSI-L/MSS, KRAS wild type colorectal cancer (CRC) who have not received a prior anti-EGFR therapy</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Phase 1b, Dose Expansion: TTX-080 monotherapy (NSCLC)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Arm 6 will enroll subjects with advanced/metastatic non-small cell lung cancer (NSCLC)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Phase 1b, Dose Expansion: TTX-080 in combination with pembrolizumab (NSCLC)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Arm 7 will enroll subjects with advanced/metastatic prior checkpoint inhibitor treated non-small cell lung cancer (NSCLC)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Phase 1b, Dose Expansion: TTX-080 as monotherapy OR in combination with pembrolizumab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Arm 8: TTX-080 monotherapy:&#xD;
Advanced/metastatic, prior checkpoint inhibitor treated renal cell carcinoma with predominance of clear cell component&#xD;
Advanced/metastatic acral melanoma&#xD;
Arm 8: TTX-080 in combination with pembrolizumab:&#xD;
• Advanced/metastatic triple-negative breast cancer (estrogen and progesterone receptor negative and HER2 negative) who has received a prior checkpoint inhibitor</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>TTX-080</intervention_name>
    <description>Variable dose (Q3W)</description>
    <arm_group_label>Phase 1a, Monotherapy Dose Escalation</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>TTX-080</intervention_name>
    <description>Specified dose (Q3W)</description>
    <arm_group_label>Phase 1b, Dose Expansion: TTX-080 as monotherapy OR in combination with pembrolizumab</arm_group_label>
    <arm_group_label>Phase 1b, Dose Expansion: TTX-080 in combination with cetuximab (CRC), no prior anti-EGFR therapy</arm_group_label>
    <arm_group_label>Phase 1b, Dose Expansion: TTX-080 in combination with cetuximab (CRC), prior anti-EGFR therapy</arm_group_label>
    <arm_group_label>Phase 1b, Dose Expansion: TTX-080 in combination with cetuximab (HNSCC)</arm_group_label>
    <arm_group_label>Phase 1b, Dose Expansion: TTX-080 in combination with pembrolizumab (HNSCC)</arm_group_label>
    <arm_group_label>Phase 1b, Dose Expansion: TTX-080 in combination with pembrolizumab (NSCLC)</arm_group_label>
    <arm_group_label>Phase 1b, Dose Expansion: TTX-080 monotherapy (CRC)</arm_group_label>
    <arm_group_label>Phase 1b, Dose Expansion: TTX-080 monotherapy (NSCLC)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>pembrolizumab</intervention_name>
    <description>Specified dose (Q3W)</description>
    <arm_group_label>Phase 1b, Dose Expansion: TTX-080 as monotherapy OR in combination with pembrolizumab</arm_group_label>
    <arm_group_label>Phase 1b, Dose Expansion: TTX-080 in combination with pembrolizumab (HNSCC)</arm_group_label>
    <arm_group_label>Phase 1b, Dose Expansion: TTX-080 in combination with pembrolizumab (NSCLC)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>cetuximab</intervention_name>
    <description>Specified dose on specified days</description>
    <arm_group_label>Phase 1b, Dose Expansion: TTX-080 in combination with cetuximab (CRC), no prior anti-EGFR therapy</arm_group_label>
    <arm_group_label>Phase 1b, Dose Expansion: TTX-080 in combination with cetuximab (CRC), prior anti-EGFR therapy</arm_group_label>
    <arm_group_label>Phase 1b, Dose Expansion: TTX-080 in combination with cetuximab (HNSCC)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Abbreviated Inclusion Criteria:&#xD;
&#xD;
          1. Subject with histological diagnosis of advanced/metastatic cancer&#xD;
&#xD;
          2. Age 18 years or older, is willing and able to provide informed consent&#xD;
&#xD;
          3. Evidence of measurable disease&#xD;
&#xD;
          4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 AND life&#xD;
             expectancy of at least 12 weeks&#xD;
&#xD;
        Abbreviated Exclusion Criteria:&#xD;
&#xD;
          1. History of allergy or hypersensitivity to study treatment components. Subjects with a&#xD;
             history of severe hypersensitivity reaction to any monoclonal antibody&#xD;
&#xD;
          2. Use of an investigational agent within 28 days prior to the first dose of study&#xD;
             treatment and throughout the study&#xD;
&#xD;
          3. Receiving high-dose systemic steroid therapy or any other form of immunosuppressive&#xD;
             therapy&#xD;
&#xD;
          4. History of severe autoimmune disease&#xD;
&#xD;
          5. Uncontrolled intercurrent illness or other active malignancy requiring ongoing&#xD;
             treatment&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Arizona Oncology Associates</name>
      <address>
        <city>Tucson</city>
        <state>Arizona</state>
        <zip>85711</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Southern California</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90033</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of California, Los Angeles</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90095</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hoag Memorial Hospital</name>
      <address>
        <city>Newport Beach</city>
        <state>California</state>
        <zip>92663</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rocky Mountain Cancer Centers</name>
      <address>
        <city>Denver</city>
        <state>Colorado</state>
        <zip>80218</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Yale Cancer Center</name>
      <address>
        <city>New Haven</city>
        <state>Connecticut</state>
        <zip>06511</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Christiana Care Helen F. Graham Cancer Center</name>
      <address>
        <city>Newark</city>
        <state>Delaware</state>
        <zip>19713</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>John Hopkins Kimmer Cancer Center</name>
      <address>
        <city>Washington</city>
        <state>District of Columbia</state>
        <zip>20016</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Florida Cancer Specialists</name>
      <address>
        <city>Daytona Beach</city>
        <state>Florida</state>
        <zip>32117</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Florida Cancer Specialists</name>
      <address>
        <city>Fleming Island</city>
        <state>Florida</state>
        <zip>32003</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ocala Oncology Center</name>
      <address>
        <city>Ocala</city>
        <state>Florida</state>
        <zip>34474</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>AdventHealth Research Institute</name>
      <address>
        <city>Orlando</city>
        <state>Florida</state>
        <zip>32804</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Illinois Cancer Specialists</name>
      <address>
        <city>Arlington Heights</city>
        <state>Illinois</state>
        <zip>60005</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Illinois</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60612</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Indiana University</name>
      <address>
        <city>Indianapolis</city>
        <state>Indiana</state>
        <zip>46202</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Norton Cancer Institute</name>
      <address>
        <city>Louisville</city>
        <state>Kentucky</state>
        <zip>40241</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Maryland Oncology Hematology</name>
      <address>
        <city>Silver Spring</city>
        <state>Maryland</state>
        <zip>20904</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Dana-Farber Cancer Institute</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02215</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>START Midwest</name>
      <address>
        <city>Grand Rapids</city>
        <state>Michigan</state>
        <zip>49546</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Regions Hospital Cancer Care Center</name>
      <address>
        <city>Saint Paul</city>
        <state>Minnesota</state>
        <zip>55101</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Washington University in St Louis</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63110</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Nebraska Cancer Center Oncology Hematology West P.C.</name>
      <address>
        <city>Omaha</city>
        <state>Nebraska</state>
        <zip>68130</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rutgers Cancer Institute of New Jersey</name>
      <address>
        <city>New Brunswick</city>
        <state>New Jersey</state>
        <zip>08903</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Icahn School of Medicine at Mount Sinai</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10029</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Stony Brook University</name>
      <address>
        <city>Stony Brook</city>
        <state>New York</state>
        <zip>11794</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Cincinnati</name>
      <address>
        <city>Cincinnati</city>
        <state>Ohio</state>
        <zip>45267</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Zangmeister Cancer Center</name>
      <address>
        <city>Columbus</city>
        <state>Ohio</state>
        <zip>43219</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The University of Toledo</name>
      <address>
        <city>Toledo</city>
        <state>Ohio</state>
        <zip>43606</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Oklahoma</name>
      <address>
        <city>Oklahoma City</city>
        <state>Oklahoma</state>
        <zip>73104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Pittsburgh Medical Center</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <zip>15232</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Medical University of South Carolina</name>
      <address>
        <city>Charleston</city>
        <state>South Carolina</state>
        <zip>29425</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sarah Cannon Research Institute</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37203</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Vanderbilt - Ingram Cancer Center</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37232</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Texas Oncology - Dallas</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75246</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The University of Texas 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>Texas Oncology - Paris</name>
      <address>
        <city>Paris</city>
        <state>Texas</state>
        <zip>75460</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>NEXT Oncology</name>
      <address>
        <city>San Antonio</city>
        <state>Texas</state>
        <zip>78229</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>NEXT Oncology Virginia</name>
      <address>
        <city>Fairfax</city>
        <state>Virginia</state>
        <zip>22031</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Northwest Medical Specialties</name>
      <address>
        <city>Tacoma</city>
        <state>Washington</state>
        <zip>98405</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Northwest Cancer Specialists</name>
      <address>
        <city>Vancouver</city>
        <state>Washington</state>
        <zip>98684</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>July 2023</verification_date>
  <study_first_submitted>July 15, 2020</study_first_submitted>
  <study_first_submitted_qc>July 21, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 24, 2020</study_first_posted>
  <last_update_submitted>July 10, 2023</last_update_submitted>
  <last_update_submitted_qc>July 10, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">July 12, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>HLA-G</keyword>
  <keyword>TTX-080</keyword>
  <keyword>Advanced Solid Tumor</keyword>
  <keyword>Cancer</keyword>
  <keyword>Ovarian Cancer</keyword>
  <keyword>Endometrial Cancer</keyword>
  <keyword>Cervical Cancer</keyword>
  <keyword>Kidney Cancer</keyword>
  <keyword>Head and Neck Squamous Cell Carcinoma</keyword>
  <keyword>Squamous Cell Lung Cancer</keyword>
  <keyword>Prostate Cancer</keyword>
  <keyword>Colorectal Cancer</keyword>
  <keyword>Gastric Cancer</keyword>
  <keyword>Breast Cancer</keyword>
  <keyword>Bladder Cancer</keyword>
  <keyword>Lung Adenocarcinoma</keyword>
  <keyword>Melanoma</keyword>
  <keyword>Metastatic Solid Tumor</keyword>
  <keyword>Renal cell carcinoma</keyword>
  <keyword>Acral melanoma</keyword>
  <keyword>Triple Negative Breast Cancer</keyword>
  <keyword>Pembrolizumab</keyword>
  <keyword>Cetuximab</keyword>
  <keyword>Antineoplastic Agents, Immunological</keyword>
  <keyword>Antineoplastic Agents</keyword>
  <keyword>Head and Neck Cancer</keyword>
  <keyword>Lung Cancer</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pembrolizumab</mesh_term>
    <mesh_term>Cetuximab</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/NCT04485013
org study id: TTX-080-001
nct id: NCT04485013
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
TTX-080-001 is a Phase 1, open label, dose escalation and dose expansion clinical study to
      determine the safety, tolerability, and recommended Phase 2 dose of TTX-080 monotherapy
      (HLA-G inhibitor) and in combination with either pembrolizumab (PD-1 inhibitor) or cetuximab
      (EGFR inhibitor) in patients with advanced refractory / resistant solid malignancies.

      The study is enrolling in the dose expansion arms.
TTX-080 is a fully human mAb designed to block the interaction of HLA-G with its known
      ligands, ILT2 and ILT4 molecules. The Phase 1a was an open label, multicenter, dose
      escalation clinical trial to determine the safety, tolerability, MTD or OBD and the RP2D of
      TTX-080 when administered as a single agent. The Phase 1b is a dose expansion of TTX-080
      monotherapy and in combination with either pembrolizumab or cetuximab in adult subjects with
      advanced refractory/resistant solid malignancies, including Head and Neck squamous cell
      carcinoma (HNSCC), Non-Small Cell Lung Cancer (NSCLC), Colorectal cancer (CRC), triple
      negative breast cancer (TNBC), renal cell carcinoma (RCC), and acral melanoma. Additionally,
      the study will seek to evaluate the pharmacokinetics and immunogenicity of TTX-080, and
      preliminary efficacy of TTX-080 as a monotherapy and in combination with pembrolizumab or
      cetuximab.

      The study is enrolling in the dose expansion cohorts.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: 1. To determine the anti-tumor activity of TTX-080 by objective response rate [complete response + partial response) for each tumor arm per RECIST 1.1
time frame: Up to 48 months
measure: Duration of Response, Progression Free Survival per RECIST 1.1
time frame: Up to 48 months
measure: Overall Survival
time frame: Up to 48 months
measure: Adverse events (AEs) as characterized by the incidence, type, frequency, severity (graded according to NCI-CTCAE v5.0), timing, seriousness, and relationship to investigational product, and/or combination therapy, and/or individual approved therapies
time frame: Up to 48 months
measure: Tolerability: The number of cycles of TTX-080 received by patients before discontinuing due to unmanageable drug reactions
time frame: Up to 48 months
measure: Serum levels of Anti Drug Antibody against TTX-080
time frame: Up to 48 months
measure: Cmax: Maximum Observed Plasma Concentration for TTX-080
time frame: Up to 48 months
measure: Tmax: Time to Reach the Cmax for TTX-080
time frame: Up to 48 months
measure: AUC(0-t): Area Under the Plasma Concentration-time Curve From Zero Time to the Last Measurable Point for TTX-080
time frame: Up to 48 months
measure: AUC(0-Inf): Area Under the Plasma Concentration-time Curve From Zero to Infinity for TTX-080
time frame: Up to 48 months
arm group label: Phase 1a, Monotherapy Dose Escalation
arm group type: Experimental
arm group label: Phase 1b, Dose Expansion: TTX-080 in combination with pembrolizumab (HNSCC)
arm group type: Experimental
description: Arm 1 will enroll subjects with advanced/metastatic, prior checkpoint inhibitor treated Head and Neck Squamous Cell Carcinoma (HNSCC)
arm group label: Phase 1b, Dose Expansion: TTX-080 in combination with cetuximab (HNSCC)
arm group type: Experimental
description: Arm 2 will enroll subjects with advanced/metastatic Head and Neck Squamous Cell Carcinoma (HNSCC)
arm group label: Phase 1b, Dose Expansion: TTX-080 monotherapy (CRC)
arm group type: Experimental
description: Arm 3 will enroll subjects with advanced/metastatic colorectal cancer (CRC)
arm group label: Phase 1b, Dose Expansion: TTX-080 in combination with cetuximab (CRC), prior anti-EGFR therapy
arm group type: Experimental
description: Arm 4 will enroll subjects with advanced/metastatic MSI-L/MSS, KRAS wild-type colorectal cancer (CRC) who have progressed on a prior anti-EGFR therapy
arm group label: Phase 1b, Dose Expansion: TTX-080 in combination with cetuximab (CRC), no prior anti-EGFR therapy
arm group type: Experimental
description: Arm 5 will enroll subjects with advanced/metastatic MSI-L/MSS, KRAS wild type colorectal cancer (CRC) who have not received a prior anti-EGFR therapy
arm group label: Phase 1b, Dose Expansion: TTX-080 monotherapy (NSCLC)
arm group type: Experimental
description: Arm 6 will enroll subjects with advanced/metastatic non-small cell lung cancer (NSCLC)
arm group label: Phase 1b, Dose Expansion: TTX-080 in combination with pembrolizumab (NSCLC)
arm group type: Experimental
description: Arm 7 will enroll subjects with advanced/metastatic prior checkpoint inhibitor treated non-small cell lung cancer (NSCLC)
arm group label: Phase 1b, Dose Expansion: TTX-080 as monotherapy OR in combination with pembrolizumab
arm group type: Experimental
description: Arm 8: TTX-080 monotherapy:
Advanced/metastatic, prior checkpoint inhibitor treated renal cell carcinoma with predominance of clear cell component
Advanced/metastatic acral melanoma
Arm 8: TTX-080 in combination with pembrolizumab:
• Advanced/metastatic triple-negative breast cancer (estrogen and progesterone receptor negative and HER2 negative) who has received a prior checkpoint inhibitor
intervention type: Drug
intervention name: TTX-080
description: Variable dose (Q3W)
arm group label: Phase 1a, Monotherapy Dose Escalation
intervention type: Drug
intervention name: TTX-080
description: Specified dose (Q3W)
arm group label: Phase 1b, Dose Expansion: TTX-080 as monotherapy OR in combination with pembrolizumab
arm group label: Phase 1b, Dose Expansion: TTX-080 in combination with cetuximab (CRC), no prior anti-EGFR therapy
arm group label: Phase 1b, Dose Expansion: TTX-080 in combination with cetuximab (CRC), prior anti-EGFR therapy
arm group label: Phase 1b, Dose Expansion: TTX-080 in combination with cetuximab (HNSCC)
arm group label: Phase 1b, Dose Expansion: TTX-080 in combination with pembrolizumab (HNSCC)
arm group label: Phase 1b, Dose Expansion: TTX-080 in combination with pembrolizumab (NSCLC)
arm group label: Phase 1b, Dose Expansion: TTX-080 monotherapy (CRC)
arm group label: Phase 1b, Dose Expansion: TTX-080 monotherapy (NSCLC)
intervention type: Drug
intervention name: pembrolizumab
description: Specified dose (Q3W)
arm group label: Phase 1b, Dose Expansion: TTX-080 as monotherapy OR in combination with pembrolizumab
arm group label: Phase 1b, Dose Expansion: TTX-080 in combination with pembrolizumab (HNSCC)
arm group label: Phase 1b, Dose Expansion: TTX-080 in combination with pembrolizumab (NSCLC)
intervention type: Drug
intervention name: cetuximab
description: Specified dose on specified days
arm group label: Phase 1b, Dose Expansion: TTX-080 in combination with cetuximab (CRC), no prior anti-EGFR therapy
arm group label: Phase 1b, Dose Expansion: TTX-080 in combination with cetuximab (CRC), prior anti-EGFR therapy
arm group label: Phase 1b, Dose Expansion: TTX-080 in combination with cetuximab (HNSCC)
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
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country: United States
responsible party type: Sponsor
mesh term: Pembrolizumab
mesh term: Cetuximab
sharing ipd: No