<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/NCT04481607</url>
  </required_header>
  <id_info>
    <org_study_id>TQB3454-I-02</org_study_id>
    <nct_id>NCT04481607</nct_id>
  </id_info>
  <brief_title>A Study to Evaluate the Tolerance, Efficacy and Pharmacokinetics of TQB3454 Tablets</brief_title>
  <official_title>A Phase I, Open-label, Dose Escalation and Expansion Study to Evaluate the Tolerance, Efficacy and Pharmacokinetics of TQB3454 Tablets</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Chia Tai Tianqing Pharmaceutical Group Co., Ltd.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Chia Tai Tianqing Pharmaceutical Group 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 open-label, multicenter, phase I study to evaluate tolerance and pharmacokinetics&#xD;
      of TQB3454 tablets in subjects with advanced solid tumor or hematologic tumor.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">August 24, 2020</start_date>
  <completion_date type="Anticipated">December 31, 2022</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2022</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>Maximum tolerated dose (MTD)</measure>
    <time_frame>Baseline up to 28 days</time_frame>
    <description>MTD was defined as the dose in which more than 2 of up to 6 patients developed a DLT.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Cmax</measure>
    <time_frame>Hour 0(pre-dose), 0.5, 1, 2, 3, 5, 8, 10, 24, 48, 72, 120, 168 hours post-dose on single dose;</time_frame>
    <description>Cmax is the maximum plasma concentration of TQB3454 or metabolite(s).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Tmax</measure>
    <time_frame>Hour 0(pre-dose), 0.5, 1, 2, 3, 5, 8, 10, 24, 48, 72, 120, 168 hours post-dose on single dose;</time_frame>
    <description>To characterize the pharmacokinetics of TQB3454 by assessment of time to reach maximum plasma concentration.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUC0-t</measure>
    <time_frame>Hour 0(pre-dose), 0.5, 1, 2, 3, 5, 8, 10, 24, 48, 72, 120, 168 hours post-dose on single dose;</time_frame>
    <description>To characterize the pharmacokinetics of TQB3454 by assessment of area under the plasma concentration time curve from zero to infinity.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Objective response rate (ORR)</measure>
    <time_frame>up to 60 weeks</time_frame>
    <description>Percentage of participants achieving complete response (CR) and partial response (PR).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression-free survival (PFS)</measure>
    <time_frame>Up to 60 weeks</time_frame>
    <description>PFS defined as the time from first dose to the first documented progressive disease (PD) or death from any cause.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>2-hydroxyglutaric acid</measure>
    <time_frame>Hour 0(pre-dose) on single dose; Hour 0(pre-dose) of day1, day8, day15, day28 on multiple dose of first cycle; hour 0(pre-dose) of day15, day28 of second and third cycle; hour 0(pre-dose) of day28 of fourth to eighth cycle.Each cycle is 28 days.</time_frame>
    <description>Correlation between 2-hydroxyglutaric acid and efficacy</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">96</enrollment>
  <condition>Advanced Solid Tumor or Hematologic Tumor</condition>
  <arm_group>
    <arm_group_label>TQB3454 tablets</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>TQB3454 tablets administered orally once. Then TQB3454 tablets administered orally, once daily in 28-day cycle after 7 days of first administration.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>TQB3454</intervention_name>
    <description>TQB3454 tablets is a small molecule oral drug.</description>
    <arm_group_label>TQB3454 tablets</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        - 1. Eastern Cooperative Oncology Group (ECOG) performance status score of 0 to 1; Life&#xD;
        expectancy ≥12 weeks.&#xD;
&#xD;
        2. Advanced solid tumors or hematological malignancy. 3. Adequate laboratory indicators. 4.&#xD;
        No pregnant or breastfeeding women, and a negative pregnancy test. 5. Understood and Signed&#xD;
        an informed consent form.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  1. Has central nervous system metastasis or system leukemia. 2.Previous anti-tumor&#xD;
             treatment:&#xD;
&#xD;
               1. Has received IDH1 mutation inhibitor.&#xD;
&#xD;
               2. Has received systemic anti-tumor therapy or radiotherapy within 14 days before&#xD;
                  the first dose.&#xD;
&#xD;
               3. Has received oral targeted drugs, less than 5 drug half-lives from first dose.&#xD;
&#xD;
               4. The related toxicity of previous anti-tumor therapy has not recovered to CTCAE ≤&#xD;
                  grade 2, except for hair loss.&#xD;
&#xD;
                  3.Complicated disease and medical history:&#xD;
&#xD;
               1. Active hepatitis B or hepatitis C.&#xD;
&#xD;
               2. Abnormal kidney.&#xD;
&#xD;
               3. Abnormal cardiovascular and cerebrovascular.&#xD;
&#xD;
               4. Abnormal gastrointestinal.&#xD;
&#xD;
               5. Has medical history of immunodeficiency.&#xD;
&#xD;
               6. Has bleeding (hemoptysis), coagulopathy, or been using warfarin, aspirin, and&#xD;
                  other antiplatelet agglutination drugs.&#xD;
&#xD;
               7. Has uncontrollable systemic bacterial, fungal or viral active infections.&#xD;
&#xD;
               8. Has medical history of idiopathic pulmonary fibrosis,or tissue pneumonia.&#xD;
&#xD;
               9. Has allergic constitution or previous severe allergy; or known allergy to&#xD;
                  ingredients of study drug.&#xD;
&#xD;
              10. Has neurological or mental disorders.&#xD;
&#xD;
              11. Has a history of drug abuse or drug addict.&#xD;
&#xD;
              12. Has received major surgery, open biopsy, or obvious traumatic injury within 4&#xD;
                  weeks before the first dose.&#xD;
&#xD;
              13. According to the judgement of the researchers, there are other factors that&#xD;
                  subjects are not suitable for the study.&#xD;
&#xD;
                  4. Has participated in other clinical trials within 30 days before participating&#xD;
                  in this trial.&#xD;
&#xD;
                  5. Female patients during pregnancy or lactation. 6. According to the judgement&#xD;
                  of the researchers, there are other factors that subjects are not suitable for&#xD;
                  the study.&#xD;
&#xD;
                  7. criteria for solid tumors:&#xD;
&#xD;
               1. Has any signs of bleeding constitution.&#xD;
&#xD;
               2. Has any CTCAE ≥ grade 3 bleeding or bleeding event,within 4 weeks before the&#xD;
                  first dose.&#xD;
&#xD;
               3. Has unhealed wounds, fractures, active ulcers of the stomach and duodenum,&#xD;
                  ulcerative colitis and other digestive tract diseases.&#xD;
&#xD;
               4. Imaging (CT or MRI) shows that the tumor has invaded the circumference of&#xD;
                  important blood vessels.&#xD;
&#xD;
               5. Has uncontrollable pleural effusion, pericardial effusion or ascites that still&#xD;
                  need repeated drainage.&#xD;
&#xD;
        criteria for blood tumor:&#xD;
&#xD;
        a) Has severe life-threatening leukemia complications.&#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_contact>
    <last_name>Lin Shen, Doctor</last_name>
    <phone>010-88196340</phone>
    <email>doctorshenlin@sina.cn</email>
  </overall_contact>
  <location>
    <facility>
      <name>Beijing Cancer Hospital</name>
      <address>
        <city>Beijing</city>
        <state>Beijing</state>
        <zip>100089</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Lin Shen, Doctor</last_name>
      <phone>010-88196340</phone>
      <email>doctorshenlin@sina.cn</email>
    </contact>
    <investigator>
      <last_name>Lin Shen, Doctor</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>The Affiliated Hosptial of Xuzhou Medical University</name>
      <address>
        <city>Xuzhou</city>
        <state>Jiangsu</state>
        <zip>221000</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Kailin Xu, doctor</last_name>
      <phone>0516-85609999</phone>
      <email>lihmd@163.com</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Tianjing Medical University Cancer Institute&amp;Hospital</name>
      <address>
        <city>Tianjin</city>
        <state>Tianjin</state>
        <zip>300020</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Yi Ba, Doctor</last_name>
      <phone>022-23909999</phone>
      <email>bayi@tjmuch.com</email>
    </contact>
    <contact_backup>
      <last_name>Yafei Wang</last_name>
      <phone>022-23909999</phone>
      <email>Drwang2005@163.com</email>
    </contact_backup>
  </location>
  <location>
    <facility>
      <name>Hematology Hospital of Chinese Academy of Medical Sciences</name>
      <address>
        <city>Tianjin</city>
        <state>Tianjin</state>
        <zip>300041</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jianxiang Wang, Doctor</last_name>
      <phone>022-23909278</phone>
      <email>wangjx@ihcams.ac.cn</email>
    </contact>
    <contact_backup>
      <last_name>Junyuan Qi, Doctor</last_name>
      <phone>022-23909067</phone>
      <email>qijy@ihcams.ac.cn</email>
    </contact_backup>
  </location>
  <location>
    <facility>
      <name>The First Affiliated Hosptial Zhejiang University School of Medical</name>
      <address>
        <city>Hangzhou</city>
        <state>Zhejiang</state>
        <zip>311100</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Yi Zheng, Doctor</last_name>
      <phone>0571-87235114</phone>
      <email>oncologist@zju.edu.cn</email>
    </contact>
    <contact_backup>
      <last_name>Jian Liu, Master</last_name>
      <phone>0571-87235114</phone>
      <email>lindaliu87@zju.edu.cn</email>
    </contact_backup>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>January 2022</verification_date>
  <study_first_submitted>July 19, 2020</study_first_submitted>
  <study_first_submitted_qc>July 19, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 22, 2020</study_first_posted>
  <last_update_submitted>January 6, 2022</last_update_submitted>
  <last_update_submitted_qc>January 6, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">January 10, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <!-- 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/NCT04481607
org study id: TQB3454-I-02
nct id: NCT04481607
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
This is a open-label, multicenter, phase I study to evaluate tolerance and pharmacokinetics
      of TQB3454 tablets in subjects with advanced solid tumor or hematologic tumor.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Maximum tolerated dose (MTD)
time frame: Baseline up to 28 days
description: MTD was defined as the dose in which more than 2 of up to 6 patients developed a DLT.
measure: Cmax
time frame: Hour 0(pre-dose), 0.5, 1, 2, 3, 5, 8, 10, 24, 48, 72, 120, 168 hours post-dose on single dose;
description: Cmax is the maximum plasma concentration of TQB3454 or metabolite(s).
measure: Tmax
time frame: Hour 0(pre-dose), 0.5, 1, 2, 3, 5, 8, 10, 24, 48, 72, 120, 168 hours post-dose on single dose;
description: To characterize the pharmacokinetics of TQB3454 by assessment of time to reach maximum plasma concentration.
measure: AUC0-t
time frame: Hour 0(pre-dose), 0.5, 1, 2, 3, 5, 8, 10, 24, 48, 72, 120, 168 hours post-dose on single dose;
description: To characterize the pharmacokinetics of TQB3454 by assessment of area under the plasma concentration time curve from zero to infinity.
measure: Objective response rate (ORR)
time frame: up to 60 weeks
description: Percentage of participants achieving complete response (CR) and partial response (PR).
measure: Progression-free survival (PFS)
time frame: Up to 60 weeks
description: PFS defined as the time from first dose to the first documented progressive disease (PD) or death from any cause.
measure: 2-hydroxyglutaric acid
time frame: Hour 0(pre-dose) on single dose; Hour 0(pre-dose) of day1, day8, day15, day28 on multiple dose of first cycle; hour 0(pre-dose) of day15, day28 of second and third cycle; hour 0(pre-dose) of day28 of fourth to eighth cycle.Each cycle is 28 days.
description: Correlation between 2-hydroxyglutaric acid and efficacy
arm group label: TQB3454 tablets
arm group type: Experimental
description: TQB3454 tablets administered orally once. Then TQB3454 tablets administered orally, once daily in 28-day cycle after 7 days of first administration.
intervention type: Drug
intervention name: TQB3454
description: TQB3454 tablets is a small molecule oral drug.
arm group label: TQB3454 tablets
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Lin Shen, Doctor
phone: 010-88196340
email: doctorshenlin@sina.cn
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
contact backup: 
facility: 
status: Recruiting
contact: 
contact backup: 
facility: 
status: Recruiting
contact: 
contact backup: 
country: China
responsible party type: Sponsor