<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/NCT04430348</url>
  </required_header>
  <id_info>
    <org_study_id>PTX35-001</org_study_id>
    <nct_id>NCT04430348</nct_id>
  </id_info>
  <brief_title>PTX-35 in Patients With Advanced Solid Tumors</brief_title>
  <official_title>PTX35-001 A Phase I, First-in-Human, Dose-Escalation Study to Evaluate the Safety of the Monoclonal Antibody PTX-35 in Patients With Advanced Solid Tumors Refractory to Standard of Care</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Pelican Therapeutics, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Heat Biologics</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      A Phase I, First-in-Human, Dose-Escalation Study to Evaluate the Safety of the Monoclonal&#xD;
      Antibody PTX-35 in Patients with Advanced Solid Tumors Refractory to Standard of Care&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is an open-label, single arm, first-in-human, Phase I study of intravenous&#xD;
      administration of PTX-35 to patients with advanced solid tumors refractory to, or ineligible&#xD;
      for, or who refuse available SOC. Five escalating dose levels of PTX-35 will be explored&#xD;
      using a traditional 3+3 design based on dose-limiting toxicities (DLTs) until optimal&#xD;
      immunological dose (OID) or maximum tolerated dose (MTD) is established.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">June 4, 2020</start_date>
  <completion_date type="Anticipated">February 2023</completion_date>
  <primary_completion_date type="Anticipated">December 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>Number of dose-limiting toxicities (DLTs) per NCI CTCAE v5.0 during the trial</measure>
    <time_frame>Up to 12 months</time_frame>
    <description>Number of dose-limiting toxicities (DLTs) per NCI CTCAE v5.0 during the trial</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Frequency of treatment-emergent adverse events (TEAEs) related to PTX-35 during the trial</measure>
    <time_frame>Up to 12 months</time_frame>
    <description>Frequency of treatment-emergent adverse events (TEAEs) related to PTX-35 during the trial</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Frequency of serious adverse events (SAEs) related to PTX-35 during the trial</measure>
    <time_frame>Up to 12 months</time_frame>
    <description>Frequency of serious adverse events (SAEs) related to PTX-35 during the trial</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Determine the optimal immunological dose (OID) of PTX-35.</measure>
    <time_frame>Up to 12 months</time_frame>
    <description>Optimal Immunological Dose (OID; dose where T-reg plateau is observed)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Determine the maximum tolerated dose (MTD) of PTX-35.</measure>
    <time_frame>Up to 12 months</time_frame>
    <description>Maximum tolerated dose (MTD; highest dose level at which ≤ 1 patient of at least 6 patients experienced a DLT during the first two treatment cycles).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Determine PK maximum concentration (Cmax)</measure>
    <time_frame>Up to 12 months</time_frame>
    <description>Determine PK maximum concentration (Cmax)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Determine PK area under curve up to the last measurable concentration (AUClast)</measure>
    <time_frame>Up to 12 months</time_frame>
    <description>Determine PK area under curve up to the last measurable concentration (AUClast)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Determine PK trough observed serum concentration (Ctrough)</measure>
    <time_frame>Up to 12 months</time_frame>
    <description>Determine PK trough observed serum concentration (Ctrough)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Determine PK terminal elimination half-life (T1/2λz)</measure>
    <time_frame>Up to 12 months</time_frame>
    <description>Determine PK terminal elimination half-life (T1/2λz)</description>
  </secondary_outcome>
  <number_of_arms>7</number_of_arms>
  <enrollment type="Anticipated">36</enrollment>
  <condition>Advanced Solid Tumor</condition>
  <arm_group>
    <arm_group_label>PTX-35 Dose Level 1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Dose Level 1: PTX-35 0.01 mg/kg</description>
  </arm_group>
  <arm_group>
    <arm_group_label>PTX-35 Dose Level 2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Dose Level 2: PTX-35 0.03 mg/kg</description>
  </arm_group>
  <arm_group>
    <arm_group_label>PTX-35 Dose Level 3</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Dose Level 3: PTX-35 0.10 mg/kg</description>
  </arm_group>
  <arm_group>
    <arm_group_label>PTX-35 Dose Level 4</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Dose Level 4: PTX-35 0.30 mg/kg</description>
  </arm_group>
  <arm_group>
    <arm_group_label>PTX-35 Dose Level 5</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Dose Level 5: PTX-35 1.0 mg/kg</description>
  </arm_group>
  <arm_group>
    <arm_group_label>PTX-35 Dose Level 6</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Dose Level 6: PTX-35 3.0 mg/kg</description>
  </arm_group>
  <arm_group>
    <arm_group_label>PTX-35 Dose Level 7</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Dose Level 7: PTX-35 10.0 mg/kg</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>PTX-35</intervention_name>
    <description>Monoclonal antibody PTX-35</description>
    <arm_group_label>PTX-35 Dose Level 1</arm_group_label>
    <arm_group_label>PTX-35 Dose Level 2</arm_group_label>
    <arm_group_label>PTX-35 Dose Level 3</arm_group_label>
    <arm_group_label>PTX-35 Dose Level 4</arm_group_label>
    <arm_group_label>PTX-35 Dose Level 5</arm_group_label>
    <arm_group_label>PTX-35 Dose Level 6</arm_group_label>
    <arm_group_label>PTX-35 Dose Level 7</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        In order to participate in this study, a patient must:&#xD;
&#xD;
          1. Be willing and have the capacity to sign the written informed consent form.&#xD;
&#xD;
          2. Be male or female of at least 18 years of age at the time of signing informed consent.&#xD;
&#xD;
          3. Have a documented diagnosis of metastatic or advanced, unresectable solid tumor&#xD;
             disease. Patient must have progressed or recurred following standard of care (SOC)&#xD;
             therapies, or are ineligible for, or who refuse other safe and effective SOC&#xD;
             therapies, and whom the Investigator believes may benefit from experimental treatment&#xD;
             with PTX-35.&#xD;
&#xD;
          4. Have an acceptable organ function, as defined below:&#xD;
&#xD;
               1. Albumin ≥ 2.5 g/dL&#xD;
&#xD;
               2. Total bilirubin &lt; 3.0 × upper limit of normal (ULN), unless patient has Gilbert's&#xD;
                  syndrome&#xD;
&#xD;
               3. Alanine transaminase (ALT) and aspartate transaminase (AST) ≤ 3.0 × ULN, or&#xD;
&#xD;
                    -  5 × ULN in the case of liver metastases&#xD;
&#xD;
               4. Calculated or measured creatinine clearance &gt; 35 mL/minute per the&#xD;
                  Cockcroft-Gault formula&#xD;
&#xD;
               5. Absolute neutrophil count ≥ 1,500/mm3&#xD;
&#xD;
               6. Hemoglobin ≥ 9 g/dL&#xD;
&#xD;
               7. Platelet count ≥ 100,000/mm3&#xD;
&#xD;
          5. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.&#xD;
&#xD;
          6. Have life expectancy of at least three months.&#xD;
&#xD;
          7. Patients, both females and males, of childbearing/reproductive potential must agree to&#xD;
             use adequate contraception while included in the trial and for six months after the&#xD;
             last treatment with PTX-35.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        In order to participate in this study, a patient must not:&#xD;
&#xD;
          1. Have received any systemic anticancer therapy including small molecules, chemotherapy,&#xD;
             radiation therapy, monoclonal antibodies or any other experimental drug within 4 weeks&#xD;
             of first dose of PTX-35. Adjuvant anti hormonal treatment(s) for prior breast cancer&#xD;
             or prostate cancer are allowed. (Note: washout for palliative radiation therapy is 2&#xD;
             weeks).&#xD;
&#xD;
          2. Have clinically significant cardiac disease, including:&#xD;
&#xD;
               1. Onset of unstable angina within 6 months of signing the Informed Consent Form&#xD;
                  (ICF).&#xD;
&#xD;
               2. Acute myocardial infarction within 6 months of the signing the ICF.&#xD;
&#xD;
               3. Known congestive heart failure (Grade III or IV as classified by the New York&#xD;
                  Heart Association); and/ or a known decreased cardiac ejection fraction (LVEF) of&#xD;
                  &lt; 45%.&#xD;
&#xD;
               4. Uncontrolled hypertension defined as systolic blood pressure ≥160 mmHg and/or&#xD;
                  diastolic blood pressure ≥ 100 mmHg, despite optimal medical management.&#xD;
&#xD;
          3. Have known or clinically suspected leptomeningeal disease. Stable, previously treated&#xD;
             metastases in the brain or spinal cord, are allowed as long as these are considered&#xD;
             stable (by CT or MRI), and not requiring systemic corticosteroids.&#xD;
&#xD;
          4. Have a history of ≥ Grade 3 allergic reactions, or suspected allergy or intolerance to&#xD;
             monoclonal antibody therapies.&#xD;
&#xD;
          5. Have a history of suspected cytokine release syndrome (CRS).&#xD;
&#xD;
          6. Have any known immunodeficiency disorders (testing not required).&#xD;
&#xD;
          7. Have received prior allogeneic stem cell transplant.&#xD;
&#xD;
          8. Have ongoing or current autoimmune disease. Permanent but stable and manageable immune&#xD;
             related adverse events (irAE) from prior therapies are permissible, if prednisone&#xD;
             equivalent corticosteroid use does not exceed 10 mg/day.&#xD;
&#xD;
          9. Have any other condition requiring concurrent systemic immunosuppressive therapy&#xD;
             (other than allowable exceptions which do not exceed 10mg/day of&#xD;
             prednisone/corticosteroid use).&#xD;
&#xD;
         10. Have clinically significant active viral, bacterial or fungal infection requiring:&#xD;
&#xD;
               1. Intravenous treatment with antimicrobial therapy completed less than two weeks&#xD;
                  prior to first dose, or&#xD;
&#xD;
               2. Oral treatment with antimicrobial therapy completed less than one week prior to&#xD;
                  first dose. Prophylactic treatment with antibiotics (e.g. for dental extractions)&#xD;
                  is allowed.&#xD;
&#xD;
         11. Have had major surgery (requiring general anesthesia or inpatient hospitalization)&#xD;
             within four weeks before first administration of PTX-35.&#xD;
&#xD;
         12. Have had a known tetanus/diphtheria vaccine within the past 10 years.&#xD;
&#xD;
         13. Have known additional malignancy that is active and/or progressive requiring&#xD;
             treatment; exceptions include basal cell or squamous cell skin cancer, in situ&#xD;
             cervical cancer, or other cancer for which the patient has been disease-free for at&#xD;
             least two years.&#xD;
&#xD;
         14. Have known previously untreated or symptomatic metastases in the brain or spinal cord&#xD;
             requiring steroids. Patients with treated and stable CNS metastases may be enrolled&#xD;
             after approval of the sponsor and/or Medical Monitor.&#xD;
&#xD;
         15. Have any other ongoing significant, uncontrolled medical condition in the opinion of&#xD;
             the Investigator.&#xD;
&#xD;
         16. Have known positive serology for human immunodeficiency virus (HIV), hepatitis B, or&#xD;
             hepatitis C (except in cases of immunity after cured infection). Testing not required.&#xD;
&#xD;
         17. Have a history of substance abuse, medical, psychological or social conditions that&#xD;
             may interfere with the patient's participation in the trial or evaluation of the trial&#xD;
             result.&#xD;
&#xD;
         18. Be a female patient who is pregnant or breast feeding.&#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>Anthony W Tolcher, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Next Oncology</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Providence Cancer Institute, Earle A. Chiles Research Institute</name>
      <address>
        <city>Portland</city>
        <state>Oregon</state>
        <zip>97213</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>NEXT Oncology Austin</name>
      <address>
        <city>Austin</city>
        <state>Texas</state>
        <zip>78705</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_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>October 2022</verification_date>
  <study_first_submitted>June 4, 2020</study_first_submitted>
  <study_first_submitted_qc>June 10, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 12, 2020</study_first_posted>
  <last_update_submitted>October 3, 2022</last_update_submitted>
  <last_update_submitted_qc>October 3, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">October 4, 2022</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>Neoplasms</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <pending_results>
    <submitted>August 16, 2023</submitted>
  </pending_results>
  <!-- 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/NCT04430348
org study id: PTX35-001
nct id: NCT04430348
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
A Phase I, First-in-Human, Dose-Escalation Study to Evaluate the Safety of the Monoclonal
      Antibody PTX-35 in Patients with Advanced Solid Tumors Refractory to Standard of Care
This is an open-label, single arm, first-in-human, Phase I study of intravenous
      administration of PTX-35 to patients with advanced solid tumors refractory to, or ineligible
      for, or who refuse available SOC. Five escalating dose levels of PTX-35 will be explored
      using a traditional 3+3 design based on dose-limiting toxicities (DLTs) until optimal
      immunological dose (OID) or maximum tolerated dose (MTD) is established.
allocation: Non-Randomized
intervention model: Sequential Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Number of dose-limiting toxicities (DLTs) per NCI CTCAE v5.0 during the trial
time frame: Up to 12 months
description: Number of dose-limiting toxicities (DLTs) per NCI CTCAE v5.0 during the trial
measure: Frequency of treatment-emergent adverse events (TEAEs) related to PTX-35 during the trial
time frame: Up to 12 months
description: Frequency of treatment-emergent adverse events (TEAEs) related to PTX-35 during the trial
measure: Frequency of serious adverse events (SAEs) related to PTX-35 during the trial
time frame: Up to 12 months
description: Frequency of serious adverse events (SAEs) related to PTX-35 during the trial
measure: Determine the optimal immunological dose (OID) of PTX-35.
time frame: Up to 12 months
description: Optimal Immunological Dose (OID; dose where T-reg plateau is observed)
measure: Determine the maximum tolerated dose (MTD) of PTX-35.
time frame: Up to 12 months
description: Maximum tolerated dose (MTD; highest dose level at which ≤ 1 patient of at least 6 patients experienced a DLT during the first two treatment cycles).
measure: Determine PK maximum concentration (Cmax)
time frame: Up to 12 months
description: Determine PK maximum concentration (Cmax)
measure: Determine PK area under curve up to the last measurable concentration (AUClast)
time frame: Up to 12 months
description: Determine PK area under curve up to the last measurable concentration (AUClast)
measure: Determine PK trough observed serum concentration (Ctrough)
time frame: Up to 12 months
description: Determine PK trough observed serum concentration (Ctrough)
measure: Determine PK terminal elimination half-life (T1/2λz)
time frame: Up to 12 months
description: Determine PK terminal elimination half-life (T1/2λz)
arm group label: PTX-35 Dose Level 1
arm group type: Experimental
description: Dose Level 1: PTX-35 0.01 mg/kg
arm group label: PTX-35 Dose Level 2
arm group type: Experimental
description: Dose Level 2: PTX-35 0.03 mg/kg
arm group label: PTX-35 Dose Level 3
arm group type: Experimental
description: Dose Level 3: PTX-35 0.10 mg/kg
arm group label: PTX-35 Dose Level 4
arm group type: Experimental
description: Dose Level 4: PTX-35 0.30 mg/kg
arm group label: PTX-35 Dose Level 5
arm group type: Experimental
description: Dose Level 5: PTX-35 1.0 mg/kg
arm group label: PTX-35 Dose Level 6
arm group type: Experimental
description: Dose Level 6: PTX-35 3.0 mg/kg
arm group label: PTX-35 Dose Level 7
arm group type: Experimental
description: Dose Level 7: PTX-35 10.0 mg/kg
intervention type: Drug
intervention name: PTX-35
description: Monoclonal antibody PTX-35
arm group label: PTX-35 Dose Level 1
arm group label: PTX-35 Dose Level 2
arm group label: PTX-35 Dose Level 3
arm group label: PTX-35 Dose Level 4
arm group label: PTX-35 Dose Level 5
arm group label: PTX-35 Dose Level 6
arm group label: PTX-35 Dose Level 7
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Anthony W Tolcher, MD
role: Principal Investigator
affiliation: Next Oncology
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Neoplasms
sharing ipd: No
submitted: August 16, 2023