<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/NCT04458389</url>
  </required_header>
  <id_info>
    <org_study_id>TY101-001</org_study_id>
    <nct_id>NCT04458389</nct_id>
  </id_info>
  <brief_title>A Phase 1/2 Study of TY101 for Locally Advanced /Metastatic Solid Tumors and Relapsed or Refractory Lymphomas</brief_title>
  <official_title>Phase 1 (Dose Escalation)/Phase 2 (Expansion Cohort) Trial of TY101 as a Single Agent in Patients With Locally Advanced/Metastatic Solid Tumors and Relapsed or Refractory Lymphomas</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Tayu Huaxia Biotech Medical Group Co., Ltd.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Tayu Huaxia Biotech Medical Group Co., Ltd.</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>
      A multicenter, open-label, dose-escalation and dose-expansion phase 1/2 study, to evaluate&#xD;
      TY101 safety, tolerability, pharmacokinetic characteristics, effectiveness and immunogenicity&#xD;
      in patients with Locally Advanced /Metastatic Solid Tumors and Relapsed or Refractory&#xD;
      Lymphomas. The study includes two parts: dose escalation and expansion cohort to evaluate the&#xD;
      tolerability and efficacy.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">December 7, 2020</start_date>
  <completion_date type="Anticipated">July 31, 2025</completion_date>
  <primary_completion_date type="Anticipated">June 30, 2024</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>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <intervention_model_description>TY101 injection</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Safety and Tolerability measured</measure>
    <time_frame>90 days after the last dose.</time_frame>
    <description>Number of Participants with treatment-related Adverse Events (AEs) by CTCAE v5.0.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Dose-limiting toxicity(DLT)</measure>
    <time_frame>3 weeks after first dose for each dose group.</time_frame>
    <description>DLT is the primary endpoint for safety in the dose escalation phase and will be used to determine the maximum tolerated dose (MTD).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics(Cmax)</measure>
    <time_frame>Up to approximately 12 months</time_frame>
    <description>Maximum Concentration(Cmax)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics(Tmax)</measure>
    <time_frame>Up to approximately 12 months</time_frame>
    <description>Dose escalation: Peak time(Tmax)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics(AUC)</measure>
    <time_frame>Up to approximately 12 months</time_frame>
    <description>Dose escalation: Area Under Curve(AUC)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics(t1/2)</measure>
    <time_frame>Up to approximately 12 months</time_frame>
    <description>Dose escalation: half life(t1/2)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics(PPK)</measure>
    <time_frame>The PPK evaluation will be further designed based on the results of the dose escalation phase.</time_frame>
    <description>Dose escalation: Population pharmacokinetics(PPK)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Objective response rate(ORR)</measure>
    <time_frame>Up to approximately 12 months</time_frame>
    <description>Efficacy observation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival(OS)</measure>
    <time_frame>Up to approximately 12 months</time_frame>
    <description>Efficacy observation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression-free survival(PFS)</measure>
    <time_frame>Up to approximately 12 months</time_frame>
    <description>Efficacy observation</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">268</enrollment>
  <condition>Locally Advanced /Metastatic Solid Tumors</condition>
  <condition>Relapsed or Refractory Lymphomas</condition>
  <arm_group>
    <arm_group_label>TY101</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Dose escalation：Humanized anti-PD-1 monoclonal antibody is to be injected intravenously 0.3mg/kg or 1mg/kg or 3mg/kg or 10mg/kg 200mg (fix dose) until disease progresses or unacceptable tolerability occurs.&#xD;
Dose expansion：After completion of the DLT observation, the sponsor and principal investigator will select a possible dose（RP2D）for dose expansion to further confirm the efficacy and safety of RP2D.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>TY101</intervention_name>
    <description>Dose escalation: TY101 0.3mg/kg or 1mg/kg or 3mg/kg or 10mg/kg 200mg Intravenous Q3W, 2 years depending on response.&#xD;
Dose expansion: Subjects received TY101 injection for a maximum of 2 years until progressive disease, intolerant toxicity, death, or withdrawal from the study occurred.</description>
    <arm_group_label>TY101</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Male or female ≥18 years&#xD;
&#xD;
          2. Willing and able to provide signed and dated informed consent prior to any&#xD;
             study-related procedures and willing and able to comply with all study procedures.&#xD;
&#xD;
          3. Histological or cytological diagnosis, advanced solid tumor and lymphoma(Dose&#xD;
             escalation phase), Or recurrence and refractory peripheral T-cell lymphoma who must&#xD;
             have failure at least 1 prior routine regimen, or failure to tolerate the toxicity, or&#xD;
             lack of any routine regimens, advanced squamous cell carcinoma of the skin and other&#xD;
             advanced solid tumors and lymphoma (Dose expansion phase）&#xD;
&#xD;
          4. At least one evaluable lesion for solid tumor or lymphoma.&#xD;
&#xD;
          5. Must provide with tumor specimen that meet the requirements for biomarker&#xD;
             testing(expression of PD-L1 and the infiltrating lymphocytes).&#xD;
&#xD;
          6. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 at the screening&#xD;
             and without deterioration within 2 weeks before enrollment.&#xD;
&#xD;
          7. Life expectancy ≥12 weeks&#xD;
&#xD;
          8. Adequate organ function as evidenced by meeting all the following requirements (with&#xD;
             14 days):&#xD;
&#xD;
               1. Hemoglobin ≥ 9.0 g/dL neutrophils ≥ 1500 cells/ µL platelets ≥ 100× 10^3/ µL;&#xD;
&#xD;
               2. Total bilirubin ≤ 1.5×upper limit of normal(ULN) aspartic transaminase (AST) and&#xD;
                  alanine transaminase (ALT) ≤ 2.5×ULN without, and ≤ 3×ULN with hepatic&#xD;
                  metastasis;&#xD;
&#xD;
               3. International Normalized Ratio (INR) ≤1.5×ULN;&#xD;
&#xD;
               4. Serum creatinine ≤1×ULN, creatinine clearance &gt;60ml/min (Cockcroft-Gault&#xD;
                  equation).&#xD;
&#xD;
          9. The results of blood pregnancy tests must be negative for premenopausal women&#xD;
             screened. All enrolled patients (male or female) should agree with adequate and&#xD;
             reliable barrier contraception from signing informed consent date to the 6 months&#xD;
             after the last dose.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Previously received any of the following therapies:&#xD;
&#xD;
             1.1 Received any other cytotoxic chemotherapeutic agents within 4 weeks prior to the&#xD;
             first dose; for nitrosoureas and mitomycin C at least 6 weeks.&#xD;
&#xD;
             1.2 Received any targeted or other anticancer drug therapy within 4 weeks prior to the&#xD;
             first dose.&#xD;
&#xD;
             1.3 Radiation therapy within 4 weeks prior to first dose (note: palliative&#xD;
             radiotherapy for bone or palliative radiotherapy for superficial lesions was allowed,&#xD;
             the course of treatment is based on local standards and had been ended 2 weeks before&#xD;
             the first dose. Radiotherapy covering more than 30% of the bone marrow area within 4&#xD;
             weeks prior to first dose was excluded).&#xD;
&#xD;
             1.4 NMPA-approved antitumor Chinese traditional medicine is in use or has been used&#xD;
             within 2 weeks prior to the first dose.&#xD;
&#xD;
          2. Concurrent malignancy within 5 years prior to screening, except for the cured basal&#xD;
             cell carcinoma or squamous cell carcinoma of the skin or carcinoma in situ of the&#xD;
             cervix.&#xD;
&#xD;
          3. Patients with active central nervous system (CNS) metastasis and/or cancerous&#xD;
             meningitis who were found on known or in the screening tests, except for the following&#xD;
             subjects: Subjects with asymptomatic brain metastasis who need to undergo regular&#xD;
             brain imaging examination as the site of the disease. Subjects with stable status of&#xD;
             brain metastasis after treatment.&#xD;
&#xD;
          4. Concomitant active or suspected autoimmune disease; but patients who are in a stable&#xD;
             state and did not require systemic immunosuppressive therapy are allowed to be&#xD;
             enrolled.&#xD;
&#xD;
          5. A history of allogeneic organ, bone marrow transplant or stem cell transplant; A&#xD;
             history of allogeneic organ, bone marrow or stem cell transplantation.&#xD;
&#xD;
          6. Patients with the history of or are suffering from pulmonary fibrosis, interstitial&#xD;
             pneumonia, pneumoconiosis, radiation pneumonia, drug-related pneumonia, severe&#xD;
             pulmonary function impairment, etc., which may interfere with the detection and&#xD;
             management of suspected drug-related pulmonary toxicity; patients with active&#xD;
             tuberculosis or with a history of active tuberculosis infection ≤48 weeks prior to&#xD;
             screening, regardless of treatment.&#xD;
&#xD;
          7. Severe cardiovascular disease, such as NYHA class III or IV congestive heart failure.&#xD;
             A history of myocardial infarction, poorly controlled arrhythmias (including QTc&#xD;
             interphase ≥450 ms in men and ≥470 ms in women, as calculated by the Fridericia&#xD;
             formula), or cerebrovascular accidents (including temporary ischemic attacks), deep&#xD;
             vein thrombosis, and pulmonary embolism in the 6 months prior to screening.&#xD;
&#xD;
          8. Uncontrolled hypertension (systolic blood pressure &gt;150 mmHg and diastolic blood&#xD;
             pressure &gt; 100 mmHg), a history of hypertension crisis, or a history of hypertensive&#xD;
             encephalopathy.&#xD;
&#xD;
          9. Uncontrolled endocrine diseases (diabetes, thyroid disease, etc.).&#xD;
&#xD;
         10. Patients with active peptic ulcer or hemorrhagic disease.&#xD;
&#xD;
         11. Seriously infected persons who need to be treated with systemic antiviral or&#xD;
             antimicrobial treatment.&#xD;
&#xD;
         12. Pericardial effusion, pleural effusion and peritoneal effusion that remained&#xD;
             uncontrolled after intervention.&#xD;
&#xD;
         13. Patients with any other severe, acute or chronic disease that the investigator&#xD;
             considers to be likely to interfere with participation in the study or evaluation and&#xD;
             which the investigator determines to be inappropriate for participation in the&#xD;
             clinical trial.&#xD;
&#xD;
         14. HIV infection.&#xD;
&#xD;
         15. Active viral hepatitis patients are excluded. Patients with serologic evidence of&#xD;
             chronic HBV infection (defined by a positive hepatitis B surface antigen test and a&#xD;
             positive anti-hepatitis core antigen antibody test, and the HBV-DNA); HCV infection&#xD;
             (defined by positive HCV antibody and HCV-RNA test).&#xD;
&#xD;
         16. The history of other therapies against immune checkpoint, such as anti-PD-1,&#xD;
             anti-PD-L1, anti-CTLA-4 or anti-LAG-3.&#xD;
&#xD;
         17. Have received steroids or other systemic immunosuppressive therapy within 14 days&#xD;
             prior to the first dose, or have to be treated while on trial; except the following:&#xD;
             a) The use of topical or inhaled corticosteroids, b) Glucocorticoids are used in the&#xD;
             short term (continuous use≤7 days) to prevent or treat non-autoimmune allergic&#xD;
             diseases.&#xD;
&#xD;
         18. History of serious allergic reaction to treatment with another monoclonal antibody.&#xD;
&#xD;
         19. A history of alcohol, drug or substance abuse.&#xD;
&#xD;
         20. Major surgery within 4 weeks prior to screening or scheduled to undergo major surgery&#xD;
             during the trial.&#xD;
&#xD;
         21. Live virus vaccine or attenuated vaccine within 30 days prior to first dose.&#xD;
&#xD;
         22. Be in the other clinical studies now, or have participated in other intervention&#xD;
             clinical trials in the previous 4 weeks.&#xD;
&#xD;
         23. Pregnant or breast-feeding females.&#xD;
&#xD;
         24. Any condition that the investigator believes may not be appropriate for participating&#xD;
             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>
  <overall_contact>
    <last_name>Guanwen Zeng, PhD</last_name>
    <phone>8610-85187670</phone>
    <email>kevintseng@tayubiotech.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>Cancer Hospital Chinese Academy of Medical Science</name>
      <address>
        <city>Beijing</city>
        <state>Beijing</state>
        <zip>100021</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Yuankai Shi, PhD.MD</last_name>
      <phone>010-87788701</phone>
      <email>syuankaipumc@126.com</email>
    </contact>
    <investigator>
      <last_name>Yuankai Shi, PhD.MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>The Fifth Medical Center of PLA General Hospital</name>
      <address>
        <city>Beijing</city>
        <state>Beijing</state>
        <zip>100071</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Hong Wang, PhD, MD</last_name>
      <phone>010-66947163</phone>
      <email>18611707961@163.com</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>West China Hospital, Sichuan University</name>
      <address>
        <city>Chengdu</city>
        <state>Sichuan</state>
        <zip>610041</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Yongsheng Wang, PhD.MD</last_name>
      <phone>18980602258</phone>
      <email>wangy756@163.com</email>
    </contact>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>May 2021</verification_date>
  <study_first_submitted>July 1, 2020</study_first_submitted>
  <study_first_submitted_qc>July 1, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 7, 2020</study_first_posted>
  <last_update_submitted>August 12, 2021</last_update_submitted>
  <last_update_submitted_qc>August 12, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">August 13, 2021</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>Lymphoma</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <!-- 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/NCT04458389
org study id: TY101-001
nct id: NCT04458389
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
A multicenter, open-label, dose-escalation and dose-expansion phase 1/2 study, to evaluate
      TY101 safety, tolerability, pharmacokinetic characteristics, effectiveness and immunogenicity
      in patients with Locally Advanced /Metastatic Solid Tumors and Relapsed or Refractory
      Lymphomas. The study includes two parts: dose escalation and expansion cohort to evaluate the
      tolerability and efficacy.
allocation: N/A
intervention model: Single Group Assignment
intervention model description: TY101 injection
primary purpose: Treatment
masking: None (Open Label)
measure: Safety and Tolerability measured
time frame: 90 days after the last dose.
description: Number of Participants with treatment-related Adverse Events (AEs) by CTCAE v5.0.
measure: Dose-limiting toxicity(DLT)
time frame: 3 weeks after first dose for each dose group.
description: DLT is the primary endpoint for safety in the dose escalation phase and will be used to determine the maximum tolerated dose (MTD).
measure: Pharmacokinetics(Cmax)
time frame: Up to approximately 12 months
description: Maximum Concentration(Cmax)
measure: Pharmacokinetics(Tmax)
time frame: Up to approximately 12 months
description: Dose escalation: Peak time(Tmax)
measure: Pharmacokinetics(AUC)
time frame: Up to approximately 12 months
description: Dose escalation: Area Under Curve(AUC)
measure: Pharmacokinetics(t1/2)
time frame: Up to approximately 12 months
description: Dose escalation: half life(t1/2)
measure: Pharmacokinetics(PPK)
time frame: The PPK evaluation will be further designed based on the results of the dose escalation phase.
description: Dose escalation: Population pharmacokinetics(PPK)
measure: Objective response rate(ORR)
time frame: Up to approximately 12 months
description: Efficacy observation
measure: Overall Survival(OS)
time frame: Up to approximately 12 months
description: Efficacy observation
measure: Progression-free survival(PFS)
time frame: Up to approximately 12 months
description: Efficacy observation
arm group label: TY101
arm group type: Experimental
description: Dose escalation：Humanized anti-PD-1 monoclonal antibody is to be injected intravenously 0.3mg/kg or 1mg/kg or 3mg/kg or 10mg/kg 200mg (fix dose) until disease progresses or unacceptable tolerability occurs.
Dose expansion：After completion of the DLT observation, the sponsor and principal investigator will select a possible dose（RP2D）for dose expansion to further confirm the efficacy and safety of RP2D.
intervention type: Drug
intervention name: TY101
description: Dose escalation: TY101 0.3mg/kg or 1mg/kg or 3mg/kg or 10mg/kg 200mg Intravenous Q3W, 2 years depending on response.
Dose expansion: Subjects received TY101 injection for a maximum of 2 years until progressive disease, intolerant toxicity, death, or withdrawal from the study occurred.
arm group label: TY101
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Guanwen Zeng, PhD
phone: 8610-85187670
email: kevintseng@tayubiotech.com
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
country: China
responsible party type: Sponsor
mesh term: Lymphoma
sharing ipd: Undecided