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/NCT06038058</url>
    </required_header>
    <id_info>
      <org_study_id>BRY812-ST-01</org_study_id>
      <nct_id>NCT06038058</nct_id>
    </id_info>
    <brief_title>A Phase I Study of BRY812 for Injection Alone in Subjects With Advanced Malignancies</brief_title>
    <official_title>A Phase I Clinical Study of the Safety, Tolerability and Efficacy of BRY812 for Injection in Patients With Advanced Malignancies</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Zhe Jiang Hisun Bioray Bio-pharmaceu tical Co.Ltd</agency>
        <agency_class>Industry</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Zhe Jiang Hisun Bioray Bio-pharmaceu tical Co.Ltd</source>
    <oversight_info>
      <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 Phase I, multicenter, open-label, single-arm and first-in-human clinical study of&#xD;
        BRY812 for injection. The study objectives are to evaluate the safety, tolerability,&#xD;
        pharmacokinetic profile, anti-tumor activity and immunogenicity of BRY812 for injection in&#xD;
        patients with advanced malignancies.&#xD;
  &#xD;
        Patients will receive treatment every 3 weeks until intolerable toxicity, disease&#xD;
        progression, pregnancy, withdrawal of informed consent, death, study discontinuation, or&#xD;
        withdrawal from the study.&#xD;
      </textblock>
    </brief_summary>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">October 2023</start_date>
    <completion_date type="Anticipated">December 2028</completion_date>
    <primary_completion_date type="Anticipated">August 2028</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>Incidence of adverse events</measure>
      <time_frame>From Day 1 to 30 days after last dose; approximately 2 years</time_frame>
      <description>An AE is any untoward medical occurrence in a patient or clinical investigational subjct administered a medicinal product and which does not necessarily have a causal relationship with this treatment.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Incidence of laboratory abnormalities</measure>
      <time_frame>From Day 1 to 30 days after last dose; approximately 2 year</time_frame>
      <description>To be summarized using descriptive statistics</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Maximum Tolerated Dose (MTD) of BRY812 for injection</measure>
      <time_frame>From the first dose to the last dose；approximately 2 year</time_frame>
      <description>Maximum Tolerated Dose (MTD) of BRY812 for injection</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Recommended phase II dose (RP2D) of BRY812 for injection</measure>
      <time_frame>From the first dose to the last dose；approximately 2 year</time_frame>
      <description>Recommended phase II dose (RP2D) of BRY812 for injection</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Incidence of dose-limiting toxicity (DLT)</measure>
      <time_frame>Through 21 days after first dose</time_frame>
      <description>Incidence of dose-limiting toxicity (DLT)</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Objective response rate (ORR)</measure>
      <time_frame>Through 1 month following last dose; approximately 2 years</time_frame>
      <description>ORR is defined as the proportion of patients with complete response (CR) or partial response (PR) per RECIST v1.1.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Progression-free survival (PFS)</measure>
      <time_frame>Up to approximately 3 years</time_frame>
      <description>PFS is defined as the time from start of study treatment to first documentation of tumor progression (clinical progression or PD per RECIST v1.1).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Overall survival (OS)</measure>
      <time_frame>Up to approximately 3 years</time_frame>
      <description>OS is defined as the time from start of study treatment to date of death due to any cause</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Duration of response (DOR)</measure>
      <time_frame>Up to approximately 3 years</time_frame>
      <description>DOR is defined as the time from start of the first documentation of objective tumor response (CR or PR) to the first documentation of tumor progression (clinical progression or progressive disease (PD) per RECIST v1.1)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Pharmacokinetic assessment</measure>
      <time_frame>Through 18 weeks after dosing</time_frame>
      <description>The concentrations of BRY812, total antibody and free monomethyl auristatin E (MMAE) in blood will be determined, and the following parameters will be calculated respectively.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Immunogenicity assessment</measure>
      <time_frame>Through 18 weeks after dosing</time_frame>
      <description>The anti-drug antibody (ADA) of BRY812 in the blood is detected, and the antibody titer of ADA-positive patients is further detected according to the situation, and whether they have neutralizing antibody (NAb) is detected if necessary.</description>
    </secondary_outcome>
    <number_of_arms>1</number_of_arms>
    <enrollment type="Anticipated">164</enrollment>
    <condition>Advanced Malignancies</condition>
    <arm_group>
      <arm_group_label>BRY812</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>BRY812 for injection</intervention_name>
      <description>BRY812 for injection will be administered by intravenous drip, tentatively once per cycle spanning 3 weeks on D1 of each cycle until intolerable toxicity, disease progression, pregnancy, withdrawal of informed consent, death, study discontinuation or withdrawal from the study. The dose of each administration will be calculated based on the weight measured prior to such administration. The dosing regimen (dosing frequency and interval) for subsequent study may be adjusted based on prior data. The intravenous drip should last for ≥ 90 min for the first dose and may be adjusted to ≥ 30 min for subsequent doses if the first dose is tolerable.</description>
      <arm_group_label>BRY812</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  (1) Subjects who voluntarily sign the informed consent form, understand the nature,&#xD;
               objectives, and procedure of the study and are able to complete the study according to&#xD;
               the protocol; (2) Male or female patients, ≥ 18 years of age (based on the date of&#xD;
               signing the informed consent form); (3) In Phase Ia: patients must have advanced solid&#xD;
               tumors confirmed by histopathology and/or cytology, who have failed to respond to&#xD;
               standard-of-care (disease progression after treatment) or who could not tolerate&#xD;
               standard-of-care, or who could not obtain effective standard-of-care or for whom there&#xD;
               was no effective standard-of-care available; (Note: the patient population and&#xD;
               inclusion criteria in phase Ib will be determined according to the data of phase Ia);&#xD;
               (4) According to RECIST v1.1 (Response Evaluation Criteria in Solid Tumors), there is&#xD;
               at least 1 measurable lesion; (5) Eastern Cooperative Oncology Group (ECOG) Status 0&#xD;
               to 1; (6) Adequate organ and bone marrow function (no treatment with cells, growth&#xD;
               factors, or transfusions within 14 days prior to the first administration), as defined&#xD;
               below:&#xD;
  &#xD;
                 1. Hematology: absolute neutrophil count (ANC) ≥ 1.5 × 109/L, platelet count (PLT) ≥&#xD;
                    100 × 109/L, hemoglobin (HGB) ≥ 90 g/L;&#xD;
  &#xD;
                 2. Liver function: serum total bilirubin (TBIL) ≤ 1.5 × upper limit of normal (ULN)&#xD;
                    (except for subjects with Gilbert syndrome, TBIL ≤ 2 × ULN in patients with liver&#xD;
                    cancer or liver metastases), alanine aminotransferase (ALT) and aspartate&#xD;
                    aminotransferase (AST) ≤ 2.5 × ULN (in patients with liver cancer or liver&#xD;
                    metastases, ALT or AST ≤ 5 × ULN);&#xD;
  &#xD;
                 3. Renal function: creatinine (Cr) ≤ 1.5 × ULN or creatinine clearance (CrCL) (based&#xD;
                    on Cockcroft-Gault equation) ≥ 60 mL/min; (7) Expected survival ≥ 12 weeks; (8)&#xD;
                    Female subjects with fertility potential must test negative for serum human&#xD;
                    chorionic gonadotropin (HCG) before they are enrolled in the study. Female&#xD;
                    subjects with fertility potential or male subjects who have a female partner must&#xD;
                    agree to maintain no pregnancy plan and take effective contraceptive measures&#xD;
                    such as condoms from the signing of ICF to 6 months after the last dose of study&#xD;
                    drug (see Annex 1 for details); females are considered fertile from menarche to&#xD;
                    menopause (at least 12 months without menstruation) unless they are permanently&#xD;
                    infertile (through hysterectomy, bilateral salpingectomy, or bilateral&#xD;
                    oophorectomy).&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  (1) Subjects who have previous severe hypersensitivity to BRY812 or known&#xD;
               hypersensitivity to any component or excipient of the study drug; (2) Subjects who&#xD;
               have previously received drugs which target LIV-1; (3) Subjects who have any active&#xD;
               infection requiring systemic therapy by intravenous infusion within 2 weeks prior to&#xD;
               the first dose of study drug; (4) Subjects who have previous or current presence of&#xD;
               two or more primary tumors (excluding cured cervical carcinoma in situ, basal cell&#xD;
               carcinoma, or squamous cell carcinoma of the skin, and other tumors that have been&#xD;
               stable for more than 5 years after treatment); (5) Subjects who have symptoms of&#xD;
               active central nervous system metastases, except those with brain parenchymal&#xD;
               metastases assessed as stable by the investigator based on the following conditions:&#xD;
  &#xD;
                 1. No seizures within &gt; 12 consecutive weeks with or without the treatment of&#xD;
                    antiepileptic drugs;&#xD;
  &#xD;
                 2. Glucocorticoids are not required;&#xD;
  &#xD;
                 3. Two consecutive MRI scans (at least 4 weeks apart) show a stable state on&#xD;
                    imaging;&#xD;
  &#xD;
                 4. Asymptomatic inactive brain metastases are newly identified where two consecutive&#xD;
                    MRI scans (at least 4 weeks apart) show a stable state on imaging;&#xD;
  &#xD;
                 5. The conditions remain stable and asymptomatic for more than 1 month after&#xD;
                    treatment; (6) Subjects with serious cardiovascular and cerebrovascular diseases&#xD;
                    and lung diseases, including but not limited to:&#xD;
  &#xD;
                 1. Stroke, intracranial hemorrhage, unstable angina pectoris, congestive heart&#xD;
                    failure (NYHA class III-IV), myocardial infarction, severe arrhythmias (such as&#xD;
                    sustained ventricular tachycardia and ventricular fibrillation), congenital long&#xD;
                    QT syndrome, torsade de pointes, and symptomatic pulmonary embolism within 6&#xD;
                    months before enrollment;&#xD;
  &#xD;
                 2. Uncontrolled hypertension (at least 2 consecutive measurements of systolic blood&#xD;
                    pressure ≥ 160 mmHg or diastolic blood pressure ≥ 100 mmHg);&#xD;
  &#xD;
                 3. Echocardiogram (ECHO) or multigated acquisition scan (MUGA) shows left&#xD;
                    ventricular ejection fraction (LVEF) &lt; 50%;&#xD;
  &#xD;
                 4. During the screening period, the mean corrected (by Fridercia's formula) QT&#xD;
                    interval on three consecutive electrocardiograms is prolonged (&gt; 450 ms in males&#xD;
                    and &gt; 470 ms in females);&#xD;
  &#xD;
                 5. Subjects who have interstitial lung diseases, severe impaired lung function,&#xD;
                    severe pulmonary fibrosis, radiation pneumonitis, and other lung diseases&#xD;
                    assessed by the investigator as clinically significant; (7) Subjects who have&#xD;
                    active gastrointestinal bleeding or severe intestinal obstruction; (8) Subjects&#xD;
                    who have undergone major surgery within 4 weeks prior to the first dose of study&#xD;
                    drug or are expected to be performed during the study; (9) Subjects who have a&#xD;
                    history of allogeneic organ transplantation or allogeneic hematopoietic stem cell&#xD;
                    transplantation; (10) Subjects who have bleeding tendency or are receiving&#xD;
                    thrombolytic or anticoagulant therapy; (11) Subjects who have used strong&#xD;
                    inhibitors or substrates of CYP3A4 and/or Pgp within 4 weeks before the first&#xD;
                    dosing or within 5 half-lives of the used drug (whichever is shorter), or who&#xD;
                    have received anti-tumor therapy or participated in other clinical studies and&#xD;
                    used other study drugs, including chemotherapy, targeted therapy, immunotherapy,&#xD;
                    biotherapy (tumor vaccines, cytokines, or growth factors for cancer control),&#xD;
                    etc.; or who have received prepared slices of Chinese crude drugs or Chinese&#xD;
                    patent medicines as anti-tumor treatment within 1 week before the first dose of&#xD;
                    study drug; (12) Subjects who have received radiation therapy, including&#xD;
                    abdominal palliative stereotactic radiotherapy, within 4 weeks prior to the first&#xD;
                    dose of study drug (non-abdominal palliative stereotactic radiotherapy within 2&#xD;
                    weeks prior to the first dose); (13) Toxicity of previous antineoplastic therapy&#xD;
                    does not resolve to grade ≤ 1 as defined by NCI-CTCAE v5.0 (except for&#xD;
                    asymptomatic abnormal laboratory findings considered by the investigator, such as&#xD;
                    elevated ALP, hyperuricemia, elevated blood glucose, etc.; except for toxicity&#xD;
                    with no safety risk determined by the investigator , such as alopecia,&#xD;
                    pigmentation, etc.); (14) Subjects who have been vaccinated with a live vaccine&#xD;
                    within 4 weeks before the first dose, or who intend to be vaccinated with a live&#xD;
                    vaccine during the study; (15) Subjects who have received more than 1 week of&#xD;
                    treatment with systemic corticosteroids (methylprednisolone &gt; 10 mg/day or an&#xD;
                    equivalent dose of other similar drug) within 2 weeks prior to the first dose of&#xD;
                    study drug; (16) Subjects who have used immunosuppressants within 2 weeks prior&#xD;
                    to the first dose or once had active autoimmune diseases or had a prior history&#xD;
                    of autoimmune diseases; (17) Subjects who test positive for Hepatitis B surface&#xD;
                    antigen (HBsAg) with HBV DNA beyond the normal range; or subjects who test&#xD;
                    positive for hepatitis B core antibody with HBV DNA beyond the upper limit of&#xD;
                    normal, but do not agree to regular DNA testing during treatment and follow-up,&#xD;
                    or do not agree to receive antiviral therapy; subjects who test positive for&#xD;
                    hepatitis C virus (HCV) antibody and HCV RNA; subjects who are seropositive for&#xD;
                    human immunodeficiency virus (HIV); subjects who have syphilis and need to&#xD;
                    receive systemic treatment; (18) Subjects who have any mental or cognitive&#xD;
                    disorders that may limit their understanding and execution of the informed&#xD;
                    consent form; (19) Subjects who are pregnant or breastfeeding; (20) Subjects who&#xD;
                    plan to donate sperm after signing the informed consent form and throughout the&#xD;
                    study period, or within 6 months after the last dose of the study drug;&#xD;
                    （21）Subjects who are not eligible for enrollment or may not be able to complete&#xD;
                    the study due to other reasons by the investigator's assessment.&#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_contact>
      <last_name>He rui Yao, PhD</last_name>
      <phone>(+86)13500018020</phone>
      <email>yaoherui@163.com</email>
    </overall_contact>
    <location>
      <facility>
        <name>Sun Yat-sen Memorial Hospital，Sun Yat-sen University</name>
        <address>
          <city>Guangzhou</city>
          <state>Guangdong</state>
          <zip>510120</zip>
          <country>China</country>
        </address>
      </facility>
      <contact>
        <last_name>He rui Yao, PhD</last_name>
        <phone>(+86)13500018020</phone>
        <email>yaoherui@163.com</email>
      </contact>
    </location>
    <location_countries>
      <country>China</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 31, 2023</study_first_submitted>
    <study_first_submitted_qc>September 7, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">September 14, 2023</study_first_posted>
    <last_update_submitted>September 7, 2023</last_update_submitted>
    <last_update_submitted_qc>September 7, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 14, 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>Neoplasms</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </patient_data>
    <!-- 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/NCT06038058
  org study id: BRY812-ST-01
  nct id: NCT06038058
  lead sponsor: 
  is fda regulated drug: No
  is fda regulated device: No
  This is a Phase I, multicenter, open-label, single-arm and first-in-human clinical study of
        BRY812 for injection. The study objectives are to evaluate the safety, tolerability,
        pharmacokinetic profile, anti-tumor activity and immunogenicity of BRY812 for injection in
        patients with advanced malignancies.
  
        Patients will receive treatment every 3 weeks until intolerable toxicity, disease
        progression, pregnancy, withdrawal of informed consent, death, study discontinuation, or
        withdrawal from the study.
  allocation: N/A
  intervention model: Single Group Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Incidence of adverse events
  time frame: From Day 1 to 30 days after last dose; approximately 2 years
  description: An AE is any untoward medical occurrence in a patient or clinical investigational subjct administered a medicinal product and which does not necessarily have a causal relationship with this treatment.
  measure: Incidence of laboratory abnormalities
  time frame: From Day 1 to 30 days after last dose; approximately 2 year
  description: To be summarized using descriptive statistics
  measure: Maximum Tolerated Dose (MTD) of BRY812 for injection
  time frame: From the first dose to the last dose；approximately 2 year
  description: Maximum Tolerated Dose (MTD) of BRY812 for injection
  measure: Recommended phase II dose (RP2D) of BRY812 for injection
  time frame: From the first dose to the last dose；approximately 2 year
  description: Recommended phase II dose (RP2D) of BRY812 for injection
  measure: Incidence of dose-limiting toxicity (DLT)
  time frame: Through 21 days after first dose
  description: Incidence of dose-limiting toxicity (DLT)
  measure: Objective response rate (ORR)
  time frame: Through 1 month following last dose; approximately 2 years
  description: ORR is defined as the proportion of patients with complete response (CR) or partial response (PR) per RECIST v1.1.
  measure: Progression-free survival (PFS)
  time frame: Up to approximately 3 years
  description: PFS is defined as the time from start of study treatment to first documentation of tumor progression (clinical progression or PD per RECIST v1.1).
  measure: Overall survival (OS)
  time frame: Up to approximately 3 years
  description: OS is defined as the time from start of study treatment to date of death due to any cause
  measure: Duration of response (DOR)
  time frame: Up to approximately 3 years
  description: DOR is defined as the time from start of the first documentation of objective tumor response (CR or PR) to the first documentation of tumor progression (clinical progression or progressive disease (PD) per RECIST v1.1)
  measure: Pharmacokinetic assessment
  time frame: Through 18 weeks after dosing
  description: The concentrations of BRY812, total antibody and free monomethyl auristatin E (MMAE) in blood will be determined, and the following parameters will be calculated respectively.
  measure: Immunogenicity assessment
  time frame: Through 18 weeks after dosing
  description: The anti-drug antibody (ADA) of BRY812 in the blood is detected, and the antibody titer of ADA-positive patients is further detected according to the situation, and whether they have neutralizing antibody (NAb) is detected if necessary.
  arm group label: BRY812
  arm group type: Experimental
  intervention type: Drug
  intervention name: BRY812 for injection
  description: BRY812 for injection will be administered by intravenous drip, tentatively once per cycle spanning 3 weeks on D1 of each cycle until intolerable toxicity, disease progression, pregnancy, withdrawal of informed consent, death, study discontinuation or withdrawal from the study. The dose of each administration will be calculated based on the weight measured prior to such administration. The dosing regimen (dosing frequency and interval) for subsequent study may be adjusted based on prior data. The intravenous drip should last for ≥ 90 min for the first dose and may be adjusted to ≥ 30 min for subsequent doses if the first dose is tolerable.
  arm group label: BRY812
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: He rui Yao, PhD
  phone: (+86)13500018020
  email: yaoherui@163.com
  facility: 
  contact: 
  country: China
  responsible party type: Sponsor
  mesh term: Neoplasms
  sharing ipd: No