xml: <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/NCT05978284</url>
    </required_header>
    <id_info>
      <org_study_id>ZG006-001</org_study_id>
      <nct_id>NCT05978284</nct_id>
    </id_info>
    <brief_title>Study of ZG006 in Participants With Small Cell Lung Cancer or Neuroendocrine Carcinoma</brief_title>
    <official_title>A Phase 1/2 Dose Escalation Study of the Tolerability, Safety, Efficacy and Pharmacokinetics of ZG006 in Participants With Small Cell Lung Cancer or Neuroendocrine Carcinoma</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Suzhou Zelgen Biopharmaceuticals Co.,Ltd</agency>
        <agency_class>Industry</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Suzhou Zelgen Biopharmaceuticals Co.,Ltd</source>
    <oversight_info>
      <has_dmc>No</has_dmc>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        This is a multi-center, open-label, Phase Ⅰ/Ⅱ clinical study of ZG006 for the treatment of&#xD;
        participants with small cell lung cancer or neuroendocrine carcinoma who had no standard&#xD;
        treatment available, or were intolerant to standard treatment.&#xD;
      </textblock>
    </brief_summary>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">September 2023</start_date>
    <completion_date type="Anticipated">October 2025</completion_date>
    <primary_completion_date type="Anticipated">September 2025</primary_completion_date>
    <phase>Phase 1/Phase 2</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>The incidence of dose-limiting toxicity (DLT)</measure>
      <time_frame>Up to 28 days</time_frame>
      <description>An event is considered to be a DLT if the event occurs within the first 28 days of treatment and meets the dose-limiting toxicity criteria</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Maximum Tolerated Dose (MTD) of ZG006</measure>
      <time_frame>Up to approximately 1 year</time_frame>
    </primary_outcome>
    <primary_outcome>
      <measure>Determine the Recommended Phase 2 Dose (RP2D)</measure>
      <time_frame>Up to approximately 1 year</time_frame>
    </primary_outcome>
    <primary_outcome>
      <measure>Number of participants with adverse events (AEs)</measure>
      <time_frame>Up to approximately 2 year</time_frame>
      <description>The types and frequencies of adverse events (AEs) evaluated according to the National Cancer Institute Common Terminology Criteria for adverse events (NCI-CTCAE) version 5.0</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Number of participants with serious adverse events (SAEs)</measure>
      <time_frame>Up to approximately 2 year</time_frame>
    </primary_outcome>
    <primary_outcome>
      <measure>Incidence of abnormal laboratory results</measure>
      <time_frame>Up to approximately 2 year</time_frame>
      <description>Abnormal laboratory results of safety concerns such as ALT, AST, Cr and BUN, et al according to NCI-CTCAE 5.0 classification.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Changes of ECGs from baselines</measure>
      <time_frame>Up to approximately 2 year</time_frame>
      <description>Changes of ECGs from baselines, such as QT interval</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Objective response rate (ORR)</measure>
      <time_frame>Up to approximately 2 year</time_frame>
      <description>ORR is defined as the percentage of participants achieving a confirmed complete response (CR) or partial response (PR) based on RECIST 1.1 criteria.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Duration of response (DOR)</measure>
      <time_frame>Up to approximately 2 year</time_frame>
      <description>DOR is defined as the time from first evidence of response (CR or PR per RECIST 1.1) to earlier date of disease progression or death due to any cause</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>disease control rate (DCR)</measure>
      <time_frame>Up to approximately 2 year</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Maximum plasma concentration (Cmax) of ZG006</measure>
      <time_frame>Baseline and up to approximately 1 year</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Time to peak concentration (Tmax)</measure>
      <time_frame>Up to approximately 1 year</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>AUC from time zero to the last quantifiable concentration after dosing (AUC[0-t]) of ZG006</measure>
      <time_frame>Up to approximately 1 year</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Terminal phase half-life (t1/2) of ZG006</measure>
      <time_frame>Up to approximately 1 year</time_frame>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">54</enrollment>
    <condition>Small Cell Lung Cancer</condition>
    <condition>Neuroendocrine Carcinoma</condition>
    <arm_group>
      <arm_group_label>Part 1: Dose Escalation</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>During the dose-escalation, an accelerated titration design (ATD) will be utilized for the first two dose groups (0.03mg and 0.1 mg), and the conventional &quot;3+3&quot; dose escalation method will be used for the subsequent dose groups. The entire duration of 28 days after the first dose of ZG006 is defined as the dose-limiting toxicity (DLT).</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Part 2: Dose Expansion</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Participants will receive the RP2D/MTD identified in Part 1 (dose exploration) of the study.</description>
    </arm_group>
    <intervention>
      <intervention_type>Biological</intervention_type>
      <intervention_name>ZG006</intervention_name>
      <description>ZG006 will be administered as an intravenous (IV) infusion.</description>
      <arm_group_label>Part 1: Dose Escalation</arm_group_label>
      <arm_group_label>Part 2: Dose Expansion</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Fully understand the study and voluntarily sign the informed consent form;&#xD;
  &#xD;
            -  Male or female 18~75 years of age;&#xD;
  &#xD;
            -  Histologically or cytologically confirmed diagnosis of small cell lung cancer (SCLC),&#xD;
               neuroendocrine carcinoma (NEC), who had no standard treatment available, or were&#xD;
               intolerant to standard treatments;&#xD;
  &#xD;
            -  Archival tissue sample or fresh biopsy tissue sample must be available for DLL3&#xD;
               detection;&#xD;
  &#xD;
            -  Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1;&#xD;
  &#xD;
            -  Life expectancy ≥ 3 months;&#xD;
  &#xD;
            -  Must have evaluable or measurable lesion. For lesions that have received radiation&#xD;
               therapy, only after the progression of the lesions, they can be considered evaluable&#xD;
               or measurable lesions;&#xD;
  &#xD;
            -  All adverse events from prior treatment have either returned to baseline or CTCAE 5.0&#xD;
               ≤ Grade 1, except for AEs not constituting a safety risk in the opinions of the&#xD;
               investigators, e.g. alopecia, hypothyroidism which can be treated with a hormone&#xD;
               replacement, etc.;&#xD;
  &#xD;
            -  Female and Male patients must agree to use a reliable form of contraception during the&#xD;
               study treatment period and for at least 6 months after the last dose of the study&#xD;
               drug.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Patients having received any of the following treatments:&#xD;
  &#xD;
          Anti-DLL3 and anti-CD3 drugs (including investigational drugs); Chemotherapy, biotherapy,&#xD;
          endocrine therapy (except for hormone replacement), and biological targeted medicines ≤ 4&#xD;
          weeks before the study entry. Local palliative radiotherapy and a small molecule targeted&#xD;
          therapy ≤ 2 weeks (or 5 half-lives, whichever is longer) before the study entry; Systemic&#xD;
          immunosuppressive medications, such as corticosteroid (doses &gt; 10 mg/day prednisone or&#xD;
          equivalent dose) within 14 days prior to the study entry; Use of any vaccines against viral&#xD;
          infections (COVID-19, influenza, varicella, etc.) within 4 weeks of study entry;&#xD;
  &#xD;
            -  Received any blood transfusion, EPO, G-CSF, albumin infusion and renal replacement&#xD;
               therapy within 14 days prior to study entry.&#xD;
  &#xD;
            -  The main organ function meets any of the following criteria within 7 days prior to&#xD;
               study entry; Hematological function: ANC &lt; 1.5×10^9/L, PLT &lt; 75×10^9/L, Hemoglobin&#xD;
               (Hb) &lt; 100 g/L; Hepatic function: Alanine aminotransferase (ALT) and aspartate&#xD;
               aminotransferase (AST) ≥ 3×ULN, ALT and AST ≥ 5×ULN for liver metastases patients;&#xD;
               Total bilirubin (TBIL) ≥ 1.5×ULN; albumin &lt; 30g/L; Creatinine clearance&#xD;
               (Cockcroft-Gault formula) &lt; 50 mL/min; INR &gt; 1.5 or APTT &gt; 1.5×ULN;&#xD;
  &#xD;
            -  Medical history, computed tomography (CT) or magnetic resonance imaging (MRI) results&#xD;
               indicate the existence of central nervous system (CNS) metastases; Note: Not&#xD;
               applicable to the following conditions: subjects with stable CNS metastases;&#xD;
  &#xD;
            -  Uncontrollable third cavity effusion (e.g. a large amount of pleural effusion,&#xD;
               ascites, or pericardial effusion, etc.) requiring repeated drainage, which was judged&#xD;
               by the investigator to be unsuitable for study;&#xD;
  &#xD;
            -  Any other malignancy within 5 years (other than radically removed and has not recurred&#xD;
               tumors including basal cell skin carcinoma, squamous cell skin carcinoma, superficial&#xD;
               bladder cancer, localized prostate cancer, cervical cancer and other cancer in situ,&#xD;
               etc.);&#xD;
  &#xD;
            -  Severe cardiac-cerebral vascular disease, including but not limited to:&#xD;
  &#xD;
          Acute myocardial infarction, unstable angina, stroke, or received coronary angioplasty or&#xD;
          stent implantation within 6 months before study entry; New York Heart Association&#xD;
          functional class II to IV congestive heart failure or left ventricular ejection fraction&#xD;
          (LVEF) &lt; 50% or the lower limit of normal; Uncontrollable hypertension (even though the&#xD;
          best treatment is used but systolic blood pressure ≥ 140 mmHg and/or diastolic blood&#xD;
          pressure ≥ 90 mmHg).&#xD;
  &#xD;
          QTc (F) interval prolonged in electrocardiography during the screening baseline period (&gt;&#xD;
          480 ms)&#xD;
  &#xD;
            -  History of autoimmune disease, including but not limited to systemic lupus&#xD;
               erythematosus, nephritis, psoriasis, rheumatoid arthritis, inflammatory bowel disease,&#xD;
               autoimmune hepatitis (except for the following: type I diabetes mellitus, skin&#xD;
               diseases that do not require systemic treatment (such as vitiligo), controllable&#xD;
               celiac disease, and childhood asthma that completely resolved in adulthood without&#xD;
               intervention);&#xD;
  &#xD;
            -  Active infection (such as acute bacterial infection, tuberculosis, active hepatitis&#xD;
               B/C, active syphilis, or active human immunodeficiency virus infection). Active&#xD;
               hepatitis B is defined as: hepatitis B virus DNA titer &gt; 10000 copies/mL or 2000&#xD;
               IU/mL; active hepatitis C is defined as: a positive hepatitis C antibody and HCV viral&#xD;
               load above the limit of quantification; active human immunodeficiency virus infection&#xD;
               is defined as: antibody positive;&#xD;
  &#xD;
            -  Active neurologic paraneoplastic syndrome;&#xD;
  &#xD;
            -  Interstitial lung disease or non-infectious pneumonitis (other than radiation-induced&#xD;
               pneumonia);&#xD;
  &#xD;
            -  Having received prior allogeneic stem cell transplantation or solid organ&#xD;
               transplantation;&#xD;
  &#xD;
            -  Known allergy to other mAbs or any antibody excipients; the history of a severe&#xD;
               allergic reaction, anaphylactoid or other hypersensitivity reactions to humanized&#xD;
               antibodies or fusion proteins;&#xD;
  &#xD;
            -  Known history of diagnosed neurological or mental disorders, for example, epilepsy,&#xD;
               dementia, etc.;&#xD;
  &#xD;
            -  A female who is pregnant or nursing;&#xD;
  &#xD;
            -  Patients were deemed unsuitable for participating in the study by the investigator for&#xD;
               any reason.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>75 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Qiming Wang</last_name>
      <role>Principal Investigator</role>
      <affiliation>Henan Cancer Hospital</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Hewen Yin</last_name>
      <phone>+86-02158942758</phone>
      <email>yinhw@zelgen.com</email>
    </overall_contact>
    <location>
      <facility>
        <name>Henan Cancer Hospital</name>
        <address>
          <city>Zhengzhou</city>
          <state>Henan</state>
          <country>China</country>
        </address>
      </facility>
    </location>
    <location_countries>
      <country>China</country>
    </location_countries>
    <verification_date>July 2023</verification_date>
    <study_first_submitted>July 28, 2023</study_first_submitted>
    <study_first_submitted_qc>July 28, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 7, 2023</study_first_posted>
    <last_update_submitted>August 6, 2023</last_update_submitted>
    <last_update_submitted_qc>August 6, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 8, 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>Lung Neoplasms</mesh_term>
      <mesh_term>Small Cell Lung Carcinoma</mesh_term>
      <mesh_term>Carcinoma, Neuroendocrine</mesh_term>
    </condition_browse>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT05978284
  org study id: ZG006-001
  nct id: NCT05978284
  lead sponsor: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  This is a multi-center, open-label, Phase Ⅰ/Ⅱ clinical study of ZG006 for the treatment of
        participants with small cell lung cancer or neuroendocrine carcinoma who had no standard
        treatment available, or were intolerant to standard treatment.
  allocation: Non-Randomized
  intervention model: Sequential Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: The incidence of dose-limiting toxicity (DLT)
  time frame: Up to 28 days
  description: An event is considered to be a DLT if the event occurs within the first 28 days of treatment and meets the dose-limiting toxicity criteria
  measure: Maximum Tolerated Dose (MTD) of ZG006
  time frame: Up to approximately 1 year
  measure: Determine the Recommended Phase 2 Dose (RP2D)
  time frame: Up to approximately 1 year
  measure: Number of participants with adverse events (AEs)
  time frame: Up to approximately 2 year
  description: The types and frequencies of adverse events (AEs) evaluated according to the National Cancer Institute Common Terminology Criteria for adverse events (NCI-CTCAE) version 5.0
  measure: Number of participants with serious adverse events (SAEs)
  time frame: Up to approximately 2 year
  measure: Incidence of abnormal laboratory results
  time frame: Up to approximately 2 year
  description: Abnormal laboratory results of safety concerns such as ALT, AST, Cr and BUN, et al according to NCI-CTCAE 5.0 classification.
  measure: Changes of ECGs from baselines
  time frame: Up to approximately 2 year
  description: Changes of ECGs from baselines, such as QT interval
  measure: Objective response rate (ORR)
  time frame: Up to approximately 2 year
  description: ORR is defined as the percentage of participants achieving a confirmed complete response (CR) or partial response (PR) based on RECIST 1.1 criteria.
  measure: Duration of response (DOR)
  time frame: Up to approximately 2 year
  description: DOR is defined as the time from first evidence of response (CR or PR per RECIST 1.1) to earlier date of disease progression or death due to any cause
  measure: disease control rate (DCR)
  time frame: Up to approximately 2 year
  measure: Maximum plasma concentration (Cmax) of ZG006
  time frame: Baseline and up to approximately 1 year
  measure: Time to peak concentration (Tmax)
  time frame: Up to approximately 1 year
  measure: AUC from time zero to the last quantifiable concentration after dosing (AUC[0-t]) of ZG006
  time frame: Up to approximately 1 year
  measure: Terminal phase half-life (t1/2) of ZG006
  time frame: Up to approximately 1 year
  arm group label: Part 1: Dose Escalation
  arm group type: Experimental
  description: During the dose-escalation, an accelerated titration design (ATD) will be utilized for the first two dose groups (0.03mg and 0.1 mg), and the conventional "3+3" dose escalation method will be used for the subsequent dose groups. The entire duration of 28 days after the first dose of ZG006 is defined as the dose-limiting toxicity (DLT).
  arm group label: Part 2: Dose Expansion
  arm group type: Experimental
  description: Participants will receive the RP2D/MTD identified in Part 1 (dose exploration) of the study.
  intervention type: Biological
  intervention name: ZG006
  description: ZG006 will be administered as an intravenous (IV) infusion.
  arm group label: Part 1: Dose Escalation
  arm group label: Part 2: Dose Expansion
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 75 Years
  healthy volunteers: No
  last name: Qiming Wang
  role: Principal Investigator
  affiliation: Henan Cancer Hospital
  last name: Hewen Yin
  phone: +86-02158942758
  email: yinhw@zelgen.com
  facility: 
  country: China
  responsible party type: Sponsor
  mesh term: Carcinoma
  mesh term: Lung Neoplasms
  mesh term: Small Cell Lung Carcinoma
  mesh term: Carcinoma, Neuroendocrine