<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/NCT04450901</url>
  </required_header>
  <id_info>
    <org_study_id>YBL006C101</org_study_id>
    <nct_id>NCT04450901</nct_id>
  </id_info>
  <brief_title>Dose Escalation/Dose Expansion Study of YBL-006 in Patients With Advanced Solid Tumors</brief_title>
  <official_title>A Phase 1/2a, Open-Label, Multicenter, Single Arm, Dose Escalation/Dose Expansion Study of YBL-006 in Patients With Advanced Solid Tumors</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Y Biologics Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Novotech (Australia) Pty Limited</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Y Biologics Inc.</source>
  <oversight_info>
    <has_dmc>Yes</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 Phase 1/2a, open-label, multicenter, dose-escalation/dose-expansion study of&#xD;
      YBL-006, in participants with Advanced Solid Tumors. This multicenter study will be conducted&#xD;
      in approximately 11-14 participants in the dose escalation phase, and approximately 39-76&#xD;
      participants in dose expansion phase.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Study will consist of three periods:&#xD;
&#xD;
        1. Screening (up to 28 days)&#xD;
&#xD;
        2. Treatment (28-day, 14-day, or 21-day cycles)&#xD;
&#xD;
        3. Follow-up (up to 3 months) The treatment period will consist of 28-day cycles for the&#xD;
           dose escalation phase, and 14-day (Cohorts B1, B2 reserve, and B3) or 21-day (Cohort B2)&#xD;
           cycles for the dose expansion phase. Each cycle is comprised of two doses of IP&#xD;
           administered as an IV infusion on Days 1 and 15 (dose escalation phase) or one dose of&#xD;
           IP administered as an IV infusion on Day 1 (dose expansion phase). The treatment&#xD;
           duration will be of 1 year in patients who are responding to the treatment.&#xD;
&#xD;
      Dose Escalation:&#xD;
&#xD;
      An accelerated titration design will be utilized for the lowest dose cohort (0.5 mg/kg) in&#xD;
      the dose escalation part. Whereas the traditional 3 + 3 design will be utilized for the&#xD;
      higher dose cohorts until the proposed starting dose for the Expansion Cohort is determined&#xD;
&#xD;
      Expansion Cohorts:&#xD;
&#xD;
      Up to four tumor-specific expansion cohorts consisting of approximately 39 to 76 participants&#xD;
      will evaluate the safety, efficacy, PK, and PD of YBL-006 at the proposed doses of YBL-006&quot;&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">July 1, 2020</start_date>
  <completion_date type="Anticipated">March 31, 2023</completion_date>
  <primary_completion_date type="Anticipated">March 31, 2023</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>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Safety and tolerability measure through Adverse Events/Serious Adverse Events</measure>
    <time_frame>Measurements at Baseline till Follow up from 90 days of last dose</time_frame>
    <description>Treatment-related adverse events as assessed by CTCAE v5.0 or higher</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Safety and tolerability(Incidence of Treatment-Emergent Adverse Events) measure through Vital Sign- blood pressure</measure>
    <time_frame>Measurements at Baseline till Follow up from 90 days of last dose</time_frame>
    <description>Measured by result of the Vital Sign- blood pressure</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Safety and tolerability(Incidence of Treatment-Emergent Adverse Events) measure through Vital Sign-heart rate</measure>
    <time_frame>Measurements at Baseline till Follow up from 90 days of last dose</time_frame>
    <description>Measured by result of the Vital Sign- heart rate</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Safety and tolerability(Incidence of Treatment-Emergent Adverse Events) measure through 12-lead ECG</measure>
    <time_frame>Measurements at Baseline till Follow up from 90 days of last dose</time_frame>
    <description>Measured by result of the ECG QT Interval</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Safety and tolerability(Incidence of Treatment-Emergent Adverse Events) measure through Physical exam</measure>
    <time_frame>Measurements at Baseline till Follow up from 90 days of last dose</time_frame>
    <description>Measured by result of the physical exam which includes general appearance, skin, eyes/ears/nose/throat, head and neck.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>To establish the recommended Phase 2 dose (RP2D) of YBL-006 in patients with advanced solid tumors</measure>
    <time_frame>Measurements at Baseline</time_frame>
    <description>Measured through increase in anti-drug antibody (ADA) levels</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>pharmacokinetic (PK) profile of YBL-006</measure>
    <time_frame>Measured at C1D1 till Follow up from 90 days of last dose</time_frame>
    <description>PK is assessed by parameter- area under the curve (AUC)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>pharmacokinetic (PK) profile of YBL-006</measure>
    <time_frame>Measured at Cycle1(each cycle is 28 days) Day1 till Follow up from 90 days of last dose</time_frame>
    <description>PK is assessed by parameter- maximum (or peak) serum concentration (Cmax)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>pharmacokinetic (PK) profile of YBL-006</measure>
    <time_frame>Measured at Cycle1(each cycle is 28 days) Day1 till Follow up from 90 days of last dose</time_frame>
    <description>PK is assessed by parameter- time of peak concentration (Tmax)</description>
  </secondary_outcome>
  <number_of_arms>8</number_of_arms>
  <enrollment type="Anticipated">90</enrollment>
  <condition>Advanced Solid Tumors</condition>
  <arm_group>
    <arm_group_label>Cohort A1 group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>YBL-006 will be administered once every 2 weeks (Q2W). Dose: 0.5 mg/kg</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort A2 group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>YBL-006 will be administered once every 2 weeks (Q2W). Dose: 2 mg/kg</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort A3 group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>YBL-006 will be administered once every 2 weeks (Q2W). Dose: 5 mg/kg</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort A4 group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>YBL-006 will be administered once every 2 weeks (Q2W). Dose: 10 mg/kg</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort B1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Tumor type: Advanced Solid tumor (unresectable, locally advanced, or metastatic and have progressed following all standard treatments or are not suitable for standard treatments).&#xD;
YBL-006 will be administered once every 2 weeks (Q2W). Dose: 200 mg</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort B2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Tumor type: Advanced Solid tumor (unresectable, locally advanced, or metastatic and have progressed following all standard treatments or are not suitable for standard treatments).&#xD;
YBL-006 will be administered once every 3 weeks (Q3W). Dose: 300 mg</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort B2 reserve</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Tumor type: Advanced Solid tumor (unresectable, locally advanced, or metastatic and have progressed following all standard treatments or are not suitable for standard treatments).&#xD;
YBL-006 will be administered once every 2 weeks (Q2W). Dose: 300 mg</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort B3</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Tumor type: Metastatic NSCLC (Non-small-cell lung carcinoma), unresectable or metastatic, MSI-H (microsatellite instability-high) or dMMR (Deficient MisMatch Repair), recurrent or metastatic HNSCC (Head and neck squamous cell carcinoma), non-clear cell RCC (renal cell carcinoma), aSCC (anal squamous cell carcinoma), uterine cervical cancer, cSCC (cutaneous squamous cell carcinoma of the skin), uterine endometrial carcinoma, TMB-H (high tumor mutation burden) tumors, epithelial tumor of the penis (squamous cell carcinoma or adenocarcinoma), neuroendocrine tumor (any origin, pancreatic or non-pancreatic), and nasopharyngeal cancer.&#xD;
YBL-006 will be administered once every 2 weeks (Q2W). Dose: 200 mg</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>YBL-006</intervention_name>
    <description>Route of Administration: IV infusion; 0.5 mg/kg Q2W</description>
    <arm_group_label>Cohort A1 group</arm_group_label>
    <other_name>Cohort A1</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>YBL-006</intervention_name>
    <description>Route of Administration: IV infusion; 2 mg/kg Q2W</description>
    <arm_group_label>Cohort A2 group</arm_group_label>
    <other_name>Cohort A2</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>YBL-006</intervention_name>
    <description>Route of Administration: IV infusion; 5 mg/kg Q2W</description>
    <arm_group_label>Cohort A3 group</arm_group_label>
    <other_name>Cohort A3</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>YBL-006</intervention_name>
    <description>Route of Administration: IV infusion; 10 mg/kg Q2W</description>
    <arm_group_label>Cohort A4 group</arm_group_label>
    <other_name>Cohort A4</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>YBL-006</intervention_name>
    <description>Route of administration : IV infusion, 200 mg Q2W</description>
    <arm_group_label>Cohort B1</arm_group_label>
    <other_name>Cohort B1</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>YBL-006</intervention_name>
    <description>Route of administration : IV infusion, 300 mg Q3W</description>
    <arm_group_label>Cohort B2</arm_group_label>
    <other_name>Cohort B2</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>YBL-006</intervention_name>
    <description>Route of administration : IV infusion, 300 mg Q2W</description>
    <arm_group_label>Cohort B2 reserve</arm_group_label>
    <other_name>Cohort B2 reserve</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>YBL-006</intervention_name>
    <description>Route of administration : IV infusion, 200mg Q2W</description>
    <arm_group_label>Cohort B3</arm_group_label>
    <other_name>Cohort B3</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Written consent on an IRB/ IEC-approved ICF prior to any study-specific evaluation.&#xD;
&#xD;
          2. Male or female aged ≥18 years (or age of legal adult, whichever is older).&#xD;
&#xD;
          3. Life expectancy of at least 3 months.&#xD;
&#xD;
          4. ECOG performance status of 0 to 1.&#xD;
&#xD;
          5. Availability of archival tumour tissue and consent to provide archival tumour for&#xD;
             retrospective biomarker analysis, or consent to undergo a fresh tumour biopsy during&#xD;
             screening. Participants who do not have an existing (archived) tumour specimen and are&#xD;
             unwilling to undergo a biopsy may be enrolled with prior approval from the Sponsor.&#xD;
&#xD;
          6. For participants in dose escalation only: Histologically confirmed solid tumours&#xD;
             (except primary CNS tumours) that are unresectable, locally advanced, or metastatic&#xD;
             and have progressed following all standard treatments or is not appropriate for&#xD;
             standard treatments.&#xD;
&#xD;
          7. Must have at least one measurable lesion based on RECIST Version 1.1. A previously&#xD;
             irradiated lesion can be considered a target lesion if the lesion is well defined,&#xD;
             measurable and there is objective evidence of interval increase in size.&#xD;
&#xD;
          8. CNS metastasis must be without evidence of progressive neurological symptoms or&#xD;
             requires increasing doses of corticosteroids to control the CNS disease for at least 4&#xD;
             weeks. If a participant requires corticosteroids for management of CNS disease, the&#xD;
             dose must have been stable with low-dose (same or less than 10 mg/day prednisone or&#xD;
             equivalent) for at least two weeks preceding C1D1.&#xD;
&#xD;
          9. Immunosuppressive doses of systemic medications, such as steroids (doses &gt; 10 mg/day&#xD;
             prednisone or equivalent) must be discontinued at least 2 weeks before IP&#xD;
             administration.&#xD;
&#xD;
         10. Prior surgery that required general anaesthesia must be completed at least 14 days&#xD;
             before IP administration. Surgery requiring local/epidural anaesthesia must be&#xD;
             completed at least 72 hours before IP administration and participants should be&#xD;
             recovered.&#xD;
&#xD;
         11. Adequate haematological and biological function, confirmed by the following laboratory&#xD;
             values:&#xD;
&#xD;
             Neutrophils ≥ 1000/μL Platelets ≥ 75,000/μL Haemoglobin ≥ 9.0 g/dL (may have been&#xD;
             transfused) Creatinine ≤ 1.5×upper limit of normal (ULN) Aspartate aminotransferase&#xD;
             (AST) ≤ 2.5×ULN (Except with liver metastasis, AST ≤ 5×ULN) Alanine aminotransferase&#xD;
             (ALT) ≤ 2.5×ULN (Except with liver metastasis, AST ≤ 5×ULN) Bilirubin ≤ 1.5×ULN&#xD;
             (except participants with Gilbert's syndrome, who must have total bilirubin &lt; 3.0&#xD;
             mg/dL).&#xD;
&#xD;
         12. Women must meet 1 of the following criteria: postmenopausal for at least 24&#xD;
             consecutive months; surgically incapable of bearing children (i.e., have had a&#xD;
             hysterectomy or bilateral oophorectomy); or utilizing a reliable form of&#xD;
             contraception. In general, the decision for appropriate methods to prevent pregnancy&#xD;
             should be determined via discussions between the Investigator and the study&#xD;
             participant. WOCBP must agree to use a reliable form of contraceptive during the study&#xD;
             Treatment Period and for at least 120 days following the last dose of IP.&#xD;
&#xD;
         13. Men must agree to the use of acceptable contraceptive use and avoid sperm donation,&#xD;
             during the study Treatment Period and for at least 180 days after the last dose of IP.&#xD;
&#xD;
         14. For the Expansion Cohort, participants enrolling must also meet the following&#xD;
             inclusion criteria:&#xD;
&#xD;
        Confirmed diagnosis of one of the following tumour types:&#xD;
&#xD;
          1. For all Expansion Cohorts (B1, B2, B2 reserve, and B3), histologically confirmed&#xD;
             advanced solid tumours (except primary CNS tumours) that are unresectable, locally&#xD;
             advanced, or metastatic and have progressed following all standard treatments, or are&#xD;
             not appropriate for standard treatments.&#xD;
&#xD;
          2. For the B3 cohort, participants must meet one of the following:&#xD;
&#xD;
               -  Participants must have progressed following at least one line of standard&#xD;
                  systemic therapy and there must not be other approved/standard therapy available&#xD;
                  that has been shown to prolong overall survival (i.e., in a randomized trial&#xD;
                  against another standard treatment or by comparison to historical controls);&#xD;
                  participants who cannot receive other standard therapy that has been shown to&#xD;
                  prolonged survival due to medical issues will be eligible, if other eligibility&#xD;
                  criteria are met; OR&#xD;
&#xD;
               -  Participants for whom no standard treatment exists that has been shown to prolong&#xD;
                  overall survival.&#xD;
&#xD;
        The following tumour types are eligible for the B3 cohort:&#xD;
&#xD;
        - Metastatic NSCLC: Histologically or cytologically confirmed diagnosis of stage IV NSCLC&#xD;
        (cases of non-squamous cell carcinoma or NSCLC of unknown subtype) with high (≥ 50%) PD-L1&#xD;
        tumour expression as determined by IHC, without EGFR sensitizing (activating) mutation by&#xD;
        PCR and anaplastic lymphoma kinase (ALK) translocation as determined by IHC or fluorescence&#xD;
        in situ hybridization (FISH). For pathologically confirmed squamous cell carcinoma, only&#xD;
        high (≥ 50%) PD-L1 tumour expression is required.&#xD;
&#xD;
        For Korea only, participants may be enrolled, provided all of the following requirements&#xD;
        are met:&#xD;
&#xD;
          -  Participants who have failed standard care of anti-cancer treatments, including&#xD;
             platinum-based chemotherapy.&#xD;
&#xD;
          -  Participants who have refused or discontinued platinum-based chemotherapy due to&#xD;
             intolerance.&#xD;
&#xD;
          -  Participants who have refused the approved immune checkpoint inhibitors as standard&#xD;
             treatment or discontinued due to intolerance. c. Unresectable or metastatic solid&#xD;
             tumours with MSI-H or dMMR, locally confirmed by polymerase chain reaction (PCR) or&#xD;
             any other appropriate method, such as IHC, in accordance with local site practices:&#xD;
&#xD;
        No additional MSI-H test is required if this test has been completed previously. However,&#xD;
        if the participant did not proceed with this test, then additional testing should be&#xD;
        completed at a local facility.&#xD;
&#xD;
        d. Histologically confirmed diagnosis of non-clear cell renal cell carcinoma (RCC), anal&#xD;
        squamous cell carcinoma (aSCC), uterine cervical cancer, cutaneous squamous cell carcinoma&#xD;
        of the skin (cSCC), uterine endometrial carcinoma, tumours which are tumour mutational&#xD;
        burden-high (TMB-H), epithelial tumour of the penis (squamous cell carcinoma or&#xD;
        adenocarcinoma), neuroendocrine tumour (any origin, pancreatic or non-pancreatic), and&#xD;
        nasopharyngeal cancers.&#xD;
&#xD;
        TMB-H: ≥ 10 mutations/megabase, determined at the local (site) laboratory is acceptable for&#xD;
        study enrolment.&#xD;
&#xD;
        e. Histologically or cytologically confirmed recurrent or metastatic HNSCC.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. History of severe hypersensitivity reactions to other monoclonal antibodies.&#xD;
&#xD;
          2. Prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-cytotoxic&#xD;
             T-lymphocyte-associated protein 4 (anti-CTLA-4) antibody, or any other antibody or&#xD;
             drug specifically targeting T-cell co-stimulation or immune checkpoint pathways.&#xD;
&#xD;
          3. Chemotherapy, radiation therapy, biological cancer therapy, or tyrosine kinase&#xD;
             inhibitor (TKI) therapy within 2 weeks or 5 half-lives (whichever is the longer)prior&#xD;
             to the first dose of IP, or who has not recovered to National Cancer Institute (NCI)-&#xD;
             Common Terminology Criteria for Adverse Events (CTCAE) version 5 or higher Grade 1 or&#xD;
             better from the AEs due to cancer therapeutics administered more than 2 weeks earlier;&#xD;
             (palliative radiation treatment with a limited field of radiation is allowed up to 14&#xD;
             days prior to first dose of YBL-006).&#xD;
&#xD;
          4. Prior malignancy active within the previous 2 years except for locally curable cancers&#xD;
             that have been apparently cured, such as basal or squamous cell skin cancer,&#xD;
             superficial bladder cancer or carcinoma in situ of the cervix or breast, or localized&#xD;
             prostate cancer.&#xD;
&#xD;
          5. Active infection (viral, bacterial, or fungal) requiring IV antimicrobial treatment&#xD;
             within 14 days before the first dose of YBL-006.&#xD;
&#xD;
          6. Has known chronic Hepatitis B (e.g., HBsAg reactive) without sufficient anti-viral&#xD;
             treatment (prior treatment duration should be more than 3 months), Hepatitis C&#xD;
             infection, or human immunodeficiency virus (HIV).&#xD;
&#xD;
          7. Has active or history of interstitial l.ng disease (ILD), or has had a history of&#xD;
             pneumonitis that has required oral or IV steroids.&#xD;
&#xD;
          8. Evidence of bleeding diathesis.&#xD;
&#xD;
          9. Any active or suspected autoimmune disease or a documented history of autoimmune&#xD;
             disease, or history of a syndrome that required systemic steroids or immunosuppressive&#xD;
             medications, except for participants with vitiligo or resolved childhood asthma/atopy.&#xD;
&#xD;
         10. Receipt of live, attenuated vaccine within 28 days prior to the first dose of IP&#xD;
             (Note: Participants, if enrolled, should not receive live vaccine during the study and&#xD;
             180 days after the last dose of IP). Vaccination with a killed vaccine is permitted at&#xD;
             any time with consultation with the Medical Monitor. Patients may receive vaccination&#xD;
             for SARS-CoV-2 (DNA or mRNA vaccine) at the discretion of the Investigator as soon as&#xD;
             they are eligible, and a vaccine is available.&#xD;
&#xD;
         11. Known current drug or alcohol abuse.&#xD;
&#xD;
         12. Apparent active or latent tuberculosis infection (purified protein derivative [PPD]&#xD;
             test is not required) as indicated by any of the following: PPD recently converted to&#xD;
             positive; chest x-ray with definitive evidence of active infectious infiltrate.&#xD;
&#xD;
         13. Presence of any other condition that may increase the risk associated with study&#xD;
             participation or may interfere with the interpretation of study results, and, in the&#xD;
             opinion of the Investigator, would make the participant inappropriate for entry into&#xD;
             the study.&#xD;
&#xD;
         14. Concurrent medical condition requiring the use of immunosuppressive medications or&#xD;
             immunosuppressive doses of systemic corticosteroids (doses 10 mg/day prednisone or&#xD;
             equivalent). Inhaled or intranasal corticosteroids (with minimal systemic absorption)&#xD;
             may be continued if the participant is on a stable dose. Non-absorbed intra-articular&#xD;
             steroid injections will be permitted.&#xD;
&#xD;
         15. Use of other investigational therapy within 28 days before IP administration.&#xD;
&#xD;
         16. Non-study related minor surgical procedure (e.g. placement of a central venous access&#xD;
             port) ≤ 5 days, or major surgical procedure ≤ 21 days, prior to first dose of IP; in&#xD;
             all cases, the participant must be sufficiently recovered and stable before treatment&#xD;
             administration.&#xD;
&#xD;
         17. Psychiatric illness or social situation that would preclude study compliance.&#xD;
&#xD;
         18. Participant has clinically significant, uncontrolled, cardiovascular disease including&#xD;
             congestive heart failure Grade III or IV according to the New York Heart Association&#xD;
             (NYHA) classification; myocardial infarction or unstable angina within the previous 6&#xD;
             months, uncontrolled hypertension, or clinically significant, uncontrolled&#xD;
             arrhythmias, including bradyarrhythmias that may cause QT prolongation (e.g., Type II&#xD;
             second degree heart block or third degree heart block).&#xD;
&#xD;
         19. Participant has a QT interval corrected using Fridericia's formula (QTcF) &gt; 470 msec.&#xD;
             Participant has a history of prolonged QT syndrome or Torsades de pointes. Participant&#xD;
             has a familial history of prolonged QT syndrome.&#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>Yoon Jaebong</last_name>
    <role>Study Director</role>
    <affiliation>Y-Biologics</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Macquarie University</name>
      <address>
        <city>Macquarie</city>
        <state>New South Wales</state>
        <zip>2109</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Seoul National University Bundang Hospital</name>
      <address>
        <city>Seongnam-si</city>
        <zip>13605</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Seoul National University Hospital</name>
      <address>
        <city>Seoul</city>
        <zip>03080</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Severance Hospital, Yonsei University Health System</name>
      <address>
        <city>Seoul</city>
        <zip>03722</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Asan Medical Center</name>
      <address>
        <city>Seoul</city>
        <zip>05505</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Samsung Medical Center</name>
      <address>
        <city>Seoul</city>
        <zip>06351</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>King Chulalongkorn Memorial Hospital</name>
      <address>
        <city>Bangkok</city>
        <zip>10330</zip>
        <country>Thailand</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Australia</country>
    <country>Korea, Republic of</country>
    <country>Thailand</country>
  </location_countries>
  <verification_date>December 2022</verification_date>
  <study_first_submitted>June 8, 2020</study_first_submitted>
  <study_first_submitted_qc>June 24, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 30, 2020</study_first_posted>
  <last_update_submitted>December 1, 2022</last_update_submitted>
  <last_update_submitted_qc>December 1, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">December 5, 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>
  <!-- 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/NCT04450901
org study id: YBL006C101
nct id: NCT04450901
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
This is a Phase 1/2a, open-label, multicenter, dose-escalation/dose-expansion study of
      YBL-006, in participants with Advanced Solid Tumors. This multicenter study will be conducted
      in approximately 11-14 participants in the dose escalation phase, and approximately 39-76
      participants in dose expansion phase.
Study will consist of three periods:

        1. Screening (up to 28 days)

        2. Treatment (28-day, 14-day, or 21-day cycles)

        3. Follow-up (up to 3 months) The treatment period will consist of 28-day cycles for the
           dose escalation phase, and 14-day (Cohorts B1, B2 reserve, and B3) or 21-day (Cohort B2)
           cycles for the dose expansion phase. Each cycle is comprised of two doses of IP
           administered as an IV infusion on Days 1 and 15 (dose escalation phase) or one dose of
           IP administered as an IV infusion on Day 1 (dose expansion phase). The treatment
           duration will be of 1 year in patients who are responding to the treatment.

      Dose Escalation:

      An accelerated titration design will be utilized for the lowest dose cohort (0.5 mg/kg) in
      the dose escalation part. Whereas the traditional 3 + 3 design will be utilized for the
      higher dose cohorts until the proposed starting dose for the Expansion Cohort is determined

      Expansion Cohorts:

      Up to four tumor-specific expansion cohorts consisting of approximately 39 to 76 participants
      will evaluate the safety, efficacy, PK, and PD of YBL-006 at the proposed doses of YBL-006"
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Safety and tolerability measure through Adverse Events/Serious Adverse Events
time frame: Measurements at Baseline till Follow up from 90 days of last dose
description: Treatment-related adverse events as assessed by CTCAE v5.0 or higher
measure: Safety and tolerability(Incidence of Treatment-Emergent Adverse Events) measure through Vital Sign- blood pressure
time frame: Measurements at Baseline till Follow up from 90 days of last dose
description: Measured by result of the Vital Sign- blood pressure
measure: Safety and tolerability(Incidence of Treatment-Emergent Adverse Events) measure through Vital Sign-heart rate
time frame: Measurements at Baseline till Follow up from 90 days of last dose
description: Measured by result of the Vital Sign- heart rate
measure: Safety and tolerability(Incidence of Treatment-Emergent Adverse Events) measure through 12-lead ECG
time frame: Measurements at Baseline till Follow up from 90 days of last dose
description: Measured by result of the ECG QT Interval
measure: Safety and tolerability(Incidence of Treatment-Emergent Adverse Events) measure through Physical exam
time frame: Measurements at Baseline till Follow up from 90 days of last dose
description: Measured by result of the physical exam which includes general appearance, skin, eyes/ears/nose/throat, head and neck.
measure: To establish the recommended Phase 2 dose (RP2D) of YBL-006 in patients with advanced solid tumors
time frame: Measurements at Baseline
description: Measured through increase in anti-drug antibody (ADA) levels
measure: pharmacokinetic (PK) profile of YBL-006
time frame: Measured at C1D1 till Follow up from 90 days of last dose
description: PK is assessed by parameter- area under the curve (AUC)
measure: pharmacokinetic (PK) profile of YBL-006
time frame: Measured at Cycle1(each cycle is 28 days) Day1 till Follow up from 90 days of last dose
description: PK is assessed by parameter- maximum (or peak) serum concentration (Cmax)
measure: pharmacokinetic (PK) profile of YBL-006
time frame: Measured at Cycle1(each cycle is 28 days) Day1 till Follow up from 90 days of last dose
description: PK is assessed by parameter- time of peak concentration (Tmax)
arm group label: Cohort A1 group
arm group type: Experimental
description: YBL-006 will be administered once every 2 weeks (Q2W). Dose: 0.5 mg/kg
arm group label: Cohort A2 group
arm group type: Experimental
description: YBL-006 will be administered once every 2 weeks (Q2W). Dose: 2 mg/kg
arm group label: Cohort A3 group
arm group type: Experimental
description: YBL-006 will be administered once every 2 weeks (Q2W). Dose: 5 mg/kg
arm group label: Cohort A4 group
arm group type: Experimental
description: YBL-006 will be administered once every 2 weeks (Q2W). Dose: 10 mg/kg
arm group label: Cohort B1
arm group type: Experimental
description: Tumor type: Advanced Solid tumor (unresectable, locally advanced, or metastatic and have progressed following all standard treatments or are not suitable for standard treatments).
YBL-006 will be administered once every 2 weeks (Q2W). Dose: 200 mg
arm group label: Cohort B2
arm group type: Experimental
description: Tumor type: Advanced Solid tumor (unresectable, locally advanced, or metastatic and have progressed following all standard treatments or are not suitable for standard treatments).
YBL-006 will be administered once every 3 weeks (Q3W). Dose: 300 mg
arm group label: Cohort B2 reserve
arm group type: Experimental
description: Tumor type: Advanced Solid tumor (unresectable, locally advanced, or metastatic and have progressed following all standard treatments or are not suitable for standard treatments).
YBL-006 will be administered once every 2 weeks (Q2W). Dose: 300 mg
arm group label: Cohort B3
arm group type: Experimental
description: Tumor type: Metastatic NSCLC (Non-small-cell lung carcinoma), unresectable or metastatic, MSI-H (microsatellite instability-high) or dMMR (Deficient MisMatch Repair), recurrent or metastatic HNSCC (Head and neck squamous cell carcinoma), non-clear cell RCC (renal cell carcinoma), aSCC (anal squamous cell carcinoma), uterine cervical cancer, cSCC (cutaneous squamous cell carcinoma of the skin), uterine endometrial carcinoma, TMB-H (high tumor mutation burden) tumors, epithelial tumor of the penis (squamous cell carcinoma or adenocarcinoma), neuroendocrine tumor (any origin, pancreatic or non-pancreatic), and nasopharyngeal cancer.
YBL-006 will be administered once every 2 weeks (Q2W). Dose: 200 mg
intervention type: Drug
intervention name: YBL-006
description: Route of Administration: IV infusion; 0.5 mg/kg Q2W
arm group label: Cohort A1 group
other name: Cohort A1
intervention type: Drug
intervention name: YBL-006
description: Route of Administration: IV infusion; 2 mg/kg Q2W
arm group label: Cohort A2 group
other name: Cohort A2
intervention type: Drug
intervention name: YBL-006
description: Route of Administration: IV infusion; 5 mg/kg Q2W
arm group label: Cohort A3 group
other name: Cohort A3
intervention type: Drug
intervention name: YBL-006
description: Route of Administration: IV infusion; 10 mg/kg Q2W
arm group label: Cohort A4 group
other name: Cohort A4
intervention type: Drug
intervention name: YBL-006
description: Route of administration : IV infusion, 200 mg Q2W
arm group label: Cohort B1
other name: Cohort B1
intervention type: Drug
intervention name: YBL-006
description: Route of administration : IV infusion, 300 mg Q3W
arm group label: Cohort B2
other name: Cohort B2
intervention type: Drug
intervention name: YBL-006
description: Route of administration : IV infusion, 300 mg Q2W
arm group label: Cohort B2 reserve
other name: Cohort B2 reserve
intervention type: Drug
intervention name: YBL-006
description: Route of administration : IV infusion, 200mg Q2W
arm group label: Cohort B3
other name: Cohort B3
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Yoon Jaebong
role: Study Director
affiliation: Y-Biologics
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Australia
country: Korea, Republic of
country: Thailand
responsible party type: Sponsor
mesh term: Neoplasms