<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/NCT03286296</url>
  </required_header>
  <id_info>
    <org_study_id>LZM009-001</org_study_id>
    <nct_id>NCT03286296</nct_id>
  </id_info>
  <brief_title>LZM009 to Treat Patients With Advanced Solid Tumors</brief_title>
  <official_title>A First-in-Human, Multicenter, Open-label, Phase 1 Dose-Escalation Study of LZM009 in Subjects With Advanced Solid Tumors</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Livzon Pharmaceutical Group Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Livzon Pharmaceutical Group 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>
      To assess the safety and tolerability of IV administered LZM009 in subjects with advanced&#xD;
      solid tumors who have progressed or are non-responsive to available therapies.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 21, 2017</start_date>
  <completion_date type="Actual">April 23, 2019</completion_date>
  <primary_completion_date type="Actual">March 6, 2019</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Determine number of patients experiencing dose limiting toxicities</measure>
    <time_frame>Day 1 through Day 28</time_frame>
    <description>And frequency and severity of DLT at LZM009 doses of 1mg/kg, 3mkg/kg and 10mkg/kg at 28 days after the first dose.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Determine Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D)</measure>
    <time_frame>17 months</time_frame>
    <description>Determination of MTD and RP2D is dependent on number of cohorts and patients experiencing DLT.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of patients experiencing clinical or laboratory adverse events as a measure of safety and tolerability</measure>
    <time_frame>Screening to 28 days after last treatment administration, or until drug related toxicities have resolved, whichever is later; or earlier than 28 days should the patient commence another anti-cancer therapy in the meantime, approximately 17 weeks.</time_frame>
    <description>Safety variables include incidence and severity of treatment emergent adverse events (TEAEs) and immune-related AEs (irAEs), vital signs measurements, clinical laboratory values and ECGs as determined by CTCAEv4.03.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Characterize the pharmacokinetics (PK) profiles of LZM009 in blood specimens of subjects with at least 1 dose</measure>
    <time_frame>Predose, 0 h, 2 h, 6h, 24h, days 3, 8, 15 and 22 post infusion of cycle 1; predose of cycle 2 and 3; pre-dose, 0 h, 2 h, 6h, days 8, and 15 post infusion of cycle 4 and predose of every other cycle after Cycle 5(one cycle=21 days except Cycle 1=28 days).</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Characterize the immunogenicity profiles of LZM009 in blood specimens of subjects with at least 1 dose</measure>
    <time_frame>Predose on C1D1, C2D1, C4D1, and at predose of every other cycle after Cycle 5, thereafter for the first 12 months, and 28 days after the last dose(one cycle=21 days except Cycle 1=28 days).</time_frame>
    <description>Presence of anti-LZM009 antibodies/neutralizing anti-LZM009 antibodies (nAbs) and effect on PK of LZM009.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assess preliminary anti-tumor activity of LZM009 in subjects with advanced solid tumors</measure>
    <time_frame>17 months</time_frame>
    <description>Overall response rate (ORR) by the Response Criteria in Solid Tumors (RECIST) v1.1.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">30</enrollment>
  <condition>Solid Tumor</condition>
  <arm_group>
    <arm_group_label>LZM009</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>LZM009,recombinant humanized anti-PD-1 monoclonal antibody for injection</intervention_name>
    <description>LZM009 doses of 1, 3, and 10 mg/kg will be administrated intravenously on day 1 and 29 and every 3 weeks thereafter until disease progression or intolerable toxicity, withdrawal of consent, or end of study</description>
    <arm_group_label>LZM009</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Patients must meet all of the following inclusion criteria to be eligible for participation&#xD;
        in this study:&#xD;
&#xD;
          1. Histologically or cytologically confirmed solid malignancy.&#xD;
&#xD;
          2. Male or non-pregnant, non-lactating female patients age ≥18 years.&#xD;
&#xD;
          3. Locally advanced or metastatic disease that is refractory to standard therapy [note&#xD;
             for patients with NSCLC patients with activating ALK translocation or EGFR mutations&#xD;
             must have been treated and failed appropriate therapy], or for which there is no&#xD;
             standard available therapy.&#xD;
&#xD;
          4. Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 2.&#xD;
&#xD;
          5. Subject with a life expectancy of ≥ 12 weeks.&#xD;
&#xD;
          6. Adequate hematologic function as indicated by&#xD;
&#xD;
               1. Platelet count ≥ 100,000/mm3&#xD;
&#xD;
               2. Hemoglobin ≥ 9.0g/dL&#xD;
&#xD;
               3. Absolute neutrophil count (ANC) ≥1000/uL Note: Use of growth-factors to maintain&#xD;
                  ANC criterion (within 28 days prior to the first dose of study drug and within 28&#xD;
                  days after day 1 of Cycle 1) is not permitted.&#xD;
&#xD;
          7. Adequate renal and liver function as indicated by:&#xD;
&#xD;
               1. Serum creatinine ≤ 1.5 x upper limit of normal (ULN); if serum creatinine is &gt;1.5&#xD;
                  x ULN, creatinine clearance must be ≥ 50 mL/min either by calculation or by&#xD;
                  measured 24-hour urine collection&#xD;
&#xD;
               2. Total bilirubin ≤1.5 x ULN; If Gilbert's Syndrome may have Bilirubin&gt; 1.5 x ULN&#xD;
&#xD;
               3. Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) ≤3 x ULN of&#xD;
                  institution's normal range; for patients with known liver metastases, AST and ALT&#xD;
                  may be ≤ 5 x ULN.&#xD;
&#xD;
               4. Coagulation: aPTT and PT≤ 1.3 x ULN&#xD;
&#xD;
          8. Patients with brain metastases are eligible if clinically controlled that is defined&#xD;
             as surgical excision and/or radiation therapy followed by 21 days of stable neurologic&#xD;
             function &amp; no evidence of CNS disease progression as determined by CT or MRI within 21&#xD;
             days prior to the first dose of study drug.&#xD;
&#xD;
          9. Willingness to use contraception by a method that is deemed effective by the&#xD;
             investigator by both males and female patients of child bearing potential&#xD;
             (postmenopausal women must have been amenorrheal for at least 12 months to be&#xD;
             considered of non-childbearing potential) and their partners throughout the treatment&#xD;
             period and for at least three months following the last dose of study drug.&#xD;
&#xD;
         10. Ability to understand and willingness to sign a written informed consent form (the&#xD;
             consent form must be signed by the patient prior to any study-specific procedures).&#xD;
&#xD;
         11. Willingness and ability to comply with study procedures and follow-up examination.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        To be eligible for entry into the study, the subject must not meet any of the exclusion&#xD;
        criteria listed below:&#xD;
&#xD;
          1. Receiving concurrent anti-cancer therapy or investigational therapy (chemotherapy,&#xD;
             radiation therapy, surgery, immunotherapy, hormonal therapy, targeted therapy,&#xD;
             biologic therapy, (with the exception of hormones for hypothyroidism, estrogen&#xD;
             replacement therapy, or LHRH agonists required to suppress serum testosterone levels).&#xD;
&#xD;
          2. Patients who have experienced a Grade 3 or higher toxicity related to prior PD-1/PD-L1&#xD;
             treatment.&#xD;
&#xD;
          3. Prior anticancer therapy less than 21 days of study entry, or 5 half-lives, whichever&#xD;
             is shorter.&#xD;
&#xD;
          4. Steroid therapy for anti-neoplastic intent within 7 days prior to the first dose of&#xD;
             study drug.&#xD;
&#xD;
          5. Continuance of toxicities due to prior radiotherapy or chemotherapy agents that do not&#xD;
             recover to ≤ Grade 1.&#xD;
&#xD;
          6. Known bleeding diathesis/disorder unless controlled.&#xD;
&#xD;
          7. Recent history of non-chemotherapy induced thrombocytopenia associated bleeding within&#xD;
             1 year prior to first dose of study drug.&#xD;
&#xD;
          8. Have active immune thrombocytopenic purpura (ITP), active autoimmune hemolytic anemia&#xD;
             (AHA), or a history of being refractory to platelet transfusions (within 1 year prior&#xD;
             to the first dose of study drug).&#xD;
&#xD;
          9. Serious gastrointestinal bleeding within 3 months.&#xD;
&#xD;
         10. Received a biologic (G-CSF, GM-CSF or erythropoietin) within 28 days prior to the&#xD;
             first dose of study drug and within 28 days after the first dose.&#xD;
&#xD;
         11. Patients with a condition requiring systemic treatment with either corticosteroids&#xD;
             (&gt;10 mg/day prednisone or equivalent) or other immunosuppressive medications within 14&#xD;
             days before the planned first dose of study drug. Inhaled or topical steroids, and&#xD;
             adrenal replacement steroid doses &gt; 10 mg daily prednisone equivalent are permitted in&#xD;
             the absence of active autoimmune disease. Ophthalmologic, nasal and intra-articular&#xD;
             injections or steroids are acceptable.&#xD;
&#xD;
         12. Failure to recover adequately, as judged by the investigator, from prior surgical&#xD;
             procedures. Patients who have had major surgery within 28 days from study entry, and&#xD;
             patients who have had minor surgery within 14 days of study entry.&#xD;
&#xD;
         13. Unstable angina, myocardial infarction, or a coronary revascularization procedure&#xD;
             within 180 days of study entry.&#xD;
&#xD;
         14. Neurologic instability per clinical evaluation due to tumor involvement of the central&#xD;
             nervous system (CNS). Patients with CNS tumors that have been treated, are&#xD;
             asymptomatic and who have discontinued steroids (for the treatment of CNS tumors)&#xD;
             for&gt;28 days may be enrolled.&#xD;
&#xD;
         15. Positive laboratory test for HBsAg or anti-HCV. Patients with anti-hepatitis B core&#xD;
             antibody are eligible if negative for HBsAg; patients positive for anti-HCV may be&#xD;
             enrolled if negative by nucleic acid amplification test.&#xD;
&#xD;
         16. Has a history of human immunodeficiency virus (HIV) antibody positive, or tests&#xD;
             positive for HIV at screening.&#xD;
&#xD;
         17. Any diagnosis of autoimmune disease. Subjects with hypothyroidism stable on hormone&#xD;
             replacement, adrenal insufficiency on steroid replacement, skin disorders (such as&#xD;
             vitiligo, psoriasis or alopecia) not requiring systemic treatment are permitted to&#xD;
             enroll.&#xD;
&#xD;
         18. Grade 3 or higher pneumonitis or neuropathy during previous treatment with&#xD;
             immunotherapy.&#xD;
&#xD;
         19. Diagnosis of fever and neutropenia within 1 week prior to study drug administration.&#xD;
&#xD;
         20. Uncontrolled concurrent illness including, but not limited to: serious uncontrolled&#xD;
             diabetes (blood glucose &gt; 250 mg/dL), symptomatic congestive heart failure, unstable&#xD;
             angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that&#xD;
             would limit compliance with the study requirements.&#xD;
&#xD;
         21. Patient has received a live, attenuated vaccine within 28 days of planned start of&#xD;
             study therapy.&#xD;
&#xD;
         22. Known allergies, hypersensitivity, or intolerance to protein-based therapies or with a&#xD;
             history of any significant drug allergy (e.g., anaphylaxis, hepatotoxicity,&#xD;
             immune-mediated thrombocytopenia or anemia), or to LZM009 recipients (refer to&#xD;
             Investigator's Brochure).&#xD;
&#xD;
         23. Currently participating and receiving study therapy or has participated in a study of&#xD;
             an investigational agent and received study therapy or used an investigational device&#xD;
             within 21 days or 5 half-lives, whichever is shorter, before the start of study&#xD;
             treatment, the exception of participants in the follow-up phase.&#xD;
&#xD;
         24. Any other condition or circumstance of that would, in the opinion of the investigator,&#xD;
             make the patient unsuitable for participation in the 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>
  <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>South Texas Accelerated Research Therapeutics</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>August 2019</verification_date>
  <study_first_submitted>September 8, 2017</study_first_submitted>
  <study_first_submitted_qc>September 13, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 18, 2017</study_first_posted>
  <last_update_submitted>August 1, 2019</last_update_submitted>
  <last_update_submitted_qc>August 1, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">August 2, 2019</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>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Antibodies</mesh_term>
    <mesh_term>Antibodies, Monoclonal</mesh_term>
  </intervention_browse>
  <!-- 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/NCT03286296
org study id: LZM009-001
nct id: NCT03286296
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
To assess the safety and tolerability of IV administered LZM009 in subjects with advanced
      solid tumors who have progressed or are non-responsive to available therapies.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Determine number of patients experiencing dose limiting toxicities
time frame: Day 1 through Day 28
description: And frequency and severity of DLT at LZM009 doses of 1mg/kg, 3mkg/kg and 10mkg/kg at 28 days after the first dose.
measure: Determine Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D)
time frame: 17 months
description: Determination of MTD and RP2D is dependent on number of cohorts and patients experiencing DLT.
measure: Number of patients experiencing clinical or laboratory adverse events as a measure of safety and tolerability
time frame: Screening to 28 days after last treatment administration, or until drug related toxicities have resolved, whichever is later; or earlier than 28 days should the patient commence another anti-cancer therapy in the meantime, approximately 17 weeks.
description: Safety variables include incidence and severity of treatment emergent adverse events (TEAEs) and immune-related AEs (irAEs), vital signs measurements, clinical laboratory values and ECGs as determined by CTCAEv4.03.
measure: Characterize the pharmacokinetics (PK) profiles of LZM009 in blood specimens of subjects with at least 1 dose
time frame: Predose, 0 h, 2 h, 6h, 24h, days 3, 8, 15 and 22 post infusion of cycle 1; predose of cycle 2 and 3; pre-dose, 0 h, 2 h, 6h, days 8, and 15 post infusion of cycle 4 and predose of every other cycle after Cycle 5(one cycle=21 days except Cycle 1=28 days).
measure: Characterize the immunogenicity profiles of LZM009 in blood specimens of subjects with at least 1 dose
time frame: Predose on C1D1, C2D1, C4D1, and at predose of every other cycle after Cycle 5, thereafter for the first 12 months, and 28 days after the last dose(one cycle=21 days except Cycle 1=28 days).
description: Presence of anti-LZM009 antibodies/neutralizing anti-LZM009 antibodies (nAbs) and effect on PK of LZM009.
measure: Assess preliminary anti-tumor activity of LZM009 in subjects with advanced solid tumors
time frame: 17 months
description: Overall response rate (ORR) by the Response Criteria in Solid Tumors (RECIST) v1.1.
arm group label: LZM009
arm group type: Experimental
intervention type: Biological
intervention name: LZM009,recombinant humanized anti-PD-1 monoclonal antibody for injection
description: LZM009 doses of 1, 3, and 10 mg/kg will be administrated intravenously on day 1 and 29 and every 3 weeks thereafter until disease progression or intolerable toxicity, withdrawal of consent, or end of study
arm group label: LZM009
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Neoplasms
mesh term: Antibodies
mesh term: Antibodies, Monoclonal