<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/NCT04433494</url>
  </required_header>
  <id_info>
    <org_study_id>TYKM1602101</org_study_id>
    <nct_id>NCT04433494</nct_id>
  </id_info>
  <brief_title>A Study of TY-302 in Patients With Advanced Solid Tumors</brief_title>
  <official_title>A Phase I Study to Evaluate the Safety, Tolerability and Pharmacokinetic Characteristics of TY-302 Capsules in Patients With Advanced Solid Tumors in China</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>TYK Medicines, Inc</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>TYK Medicines, Inc</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The primary objective of this study is to evaluate the safety and tolerability of TY-302&#xD;
      single and the combination with Tamoxifen in dose-escalation and dose-expansion study.The&#xD;
      drugs involved in this study are:&#xD;
&#xD;
        -  TY-302&#xD;
&#xD;
        -  Tamoxifen&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is an open-label, single-arm, phase I trial. The purpose of this study is to :&#xD;
&#xD;
        -  Test a safe and tolerable dose of TY-302 single and the combination with Tamoxifen&#xD;
&#xD;
        -  Determine the response rate of the combination&#xD;
&#xD;
        -  Further evaluate the safety and side effect profile for the combination of TY-302 and&#xD;
           Tamoxifen.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">December 7, 2020</start_date>
  <completion_date type="Anticipated">December 2023</completion_date>
  <primary_completion_date type="Anticipated">May 2023</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) and Recommended Phase 2 Dose (RP2D) of TY-302</measure>
    <time_frame>1 year</time_frame>
    <description>To determine the MTD and RP2D of TY-302 in subjects with solid tumors</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Dose Limiting Toxicity (DLT) of TY-302</measure>
    <time_frame>First 35 days of dosing</time_frame>
    <description>Incidence of Dose Limiting Toxicity (DLT) of TY-302</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D) of TY-302 combine with Tamoxifen</measure>
    <time_frame>1 year</time_frame>
    <description>To determine the MTD and RP2D of TY-302 and Tamoxifen on the combination in subjects with breast cancer</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Dose Limiting Toxicity (DLT) of TY-302 combine with Tamoxifen</measure>
    <time_frame>First 28 days of dosing</time_frame>
    <description>Incidence of Dose Limiting Toxicity (DLT) of TY-302 and Tamoxifen on the combination</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Overall Response Rate (ORR) of TY-302 combine with Tamoxifen</measure>
    <time_frame>6 months</time_frame>
    <description>To assess the effect of TY-302 combine with Tamoxifen on ORR( the proportion of patients with a best overall response of complete response (CR) or partial response (PR) assessment in accordance to Response Evaluation Criteria in Solid Tumors (RECIST 1.1) ) in the treatment of ER+/HER2- advanced breast cancer.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Disease Control Rate(DCR) of TY-302 combine with Tamoxifen</measure>
    <time_frame>9 months</time_frame>
    <description>To assess the effect of TY-302 combine with Tamoxifen on DCR(the proportion of patients with CR, PR, or stable disease(SD) assessment in accordance to RECIST 1.1) in the treatment of ER+/HER2- advanced breast cancer.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Duration of Response (DOR) of TY-302 combine with Tamoxifen</measure>
    <time_frame>9 months</time_frame>
    <description>To assess the effect of TY-302 combine with Tamoxifen on DOR( the time from first documented response (PR or CR) to the date of first documented disease progression or death due to any cause determined by Investigator assessment in accordance to RECIST 1.1) in the treatment of ER+/HER2- advanced breast cancer.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Progression-free Survival (PFS) of TY-302 combine with Tamoxifen</measure>
    <time_frame>12 months</time_frame>
    <description>To assess the effect of TY-302 combine with Tamoxifen on PFS(time from date of first dose of study treatment to date of first documented disease progression or death due to any cause determined by Investigator assessment in accordance to RECIST 1.1) in the treatment of ER+/HER2- advanced breast cancer.</description>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">60</enrollment>
  <condition>Breast Cancer</condition>
  <condition>Solid Tumor</condition>
  <arm_group>
    <arm_group_label>TY-302 ; TY-302 combine with Tamoxifen</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>TY-302&#xD;
Find the maximum tolerated dose(MTD) and the recommended phase 2 dose (RP2D) of TY-302, given orally.&#xD;
Increased dose cohorts from low dose to MTD, starting at 25mg daily.&#xD;
TY-302 combine withTamoxifen in dose-escalation stage&#xD;
TY-302: RP2D-1to RP2D daily for 28 days of each 28 day cycle.&#xD;
Tamoxifen: 20mg twice daily for 28 days of each 28 day cycle.&#xD;
TY-302 combine withTamoxifen in dose-expansion stage&#xD;
TY-302: RP2D daily for 28 days of each 28 day cycle.&#xD;
Tamoxifen: 20mg twice daily for 28 days of each 28 day cycle.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>TY-302: capsule, 25mg/50mg ; Tamoxifen: tablet,10mg</intervention_name>
    <description>TY-302 is taken orally. Tamoxifen is taken orally.</description>
    <arm_group_label>TY-302 ; TY-302 combine with Tamoxifen</arm_group_label>
    <other_name>TY-302</other_name>
    <other_name>Tamoxifen Citrate</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. 18-70years old, male or female with solid tumors, female with breast cancer&#xD;
&#xD;
          2. Histological or cytological confirmation diagnosis of advanced solid tumors (except&#xD;
             small cell lung cancer and eye cancer) in TY-302 alone study; and advanced breast&#xD;
             cancer in the combination study.&#xD;
&#xD;
          3. Biopsy proven diagnosis of ER and/or PR positive, HER2 negative.&#xD;
&#xD;
          4. At least one measurable lesion according to Response Evaluation Criteria in Solid&#xD;
             Tumours (RECIST) version 1.1.&#xD;
&#xD;
          5. Eastern Cooperative Oncology Group (ECOG) performance score 0 or 1.&#xD;
&#xD;
          6. Life expectancy of at least 3 month.&#xD;
&#xD;
          7. Adequate organ function as defined by the following criteria:&#xD;
&#xD;
             Serum aspartate transaminase (AST) and serum alanine transaminase (ALT) ≤2.5 x upper&#xD;
             limit of normal (ULN), or AST and ALT ≤5 x ULN if liver function abnormalities are due&#xD;
             to underlying malignancy; total serum bilirubin ≤1.5 x ULN; Absolute neutrophil count&#xD;
             (ANC) ≥1.5×109/L; platelets(PLT)≥75×109/L ; Hemoglobin(Hb) ≥ 90g/L; Serum creatinine&#xD;
             ≤1.5 x ULN; Left ejection fraction (LVEF)≥50%; QTc≤470 msec (based on the mean value&#xD;
             of the triplicate ECGs).&#xD;
&#xD;
          8. Female subjects have a negative urine or serum pregnancy.&#xD;
&#xD;
          9. Provision of signed and dated, written informed consent prior to any study specific&#xD;
             procedures, sampling and analyses.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Subjects presenting with any of the following were not to be included in the study:&#xD;
&#xD;
          1. Previously treated by other CDK4/6 inhibitor.&#xD;
&#xD;
          2. Hypersensitivity to TY-302(or Tamoxifen in the combination study) or to any of its&#xD;
             excipients.&#xD;
&#xD;
          3. Ocular fundus diseases in the combination study.&#xD;
&#xD;
          4. Uncontrolled intercurrent illness including active infection, human immunodeficiency&#xD;
             virus infection, active hepatitis or other severe acute or chronic medical or&#xD;
             psychiatric condition.&#xD;
&#xD;
          5. Current alcohol/drug abuse or dependence.&#xD;
&#xD;
          6. Any of the following in the previous 6 months: myocardial infarction, severe/unstable&#xD;
             angina, ongoing cardiac dysrhythmias of NCI CTCAE grade≥2, atrial fibrillation of any&#xD;
             grade, coronary/peripheral artery bypass graft, symptomatic congestive heart failure&#xD;
             of NCI CTCAE grade≥2, cerebrovascular accident.&#xD;
&#xD;
          7. Presence of a condition that would interfere with enteric absorption of TY-302 and/or&#xD;
             Tamoxifen.&#xD;
&#xD;
          8. Any cytotoxic chemotherapy, investigational agents or anticancer drugs for the&#xD;
             treatment from a previous treatment regimen within 4 weeks of the first dose.&#xD;
&#xD;
          9. Spinal cord compression or brain metastases unless asymptomatic.&#xD;
&#xD;
         10. Major surgery within 8 weeks of first study treatment.&#xD;
&#xD;
         11. Current use or anticipated need for drugs that are known strong CYP3A4 inhibitors,&#xD;
             strong CYP3A4 inducers, Narrow therapeutic index for CYP3A sensitive substrates,&#xD;
             CYP2D6 inhibitors, CYP2D6 inducers.&#xD;
&#xD;
         12. Patients on chronic anticoagulation.&#xD;
&#xD;
         13. The subject inappropriate for entry into this study in the judgment of the&#xD;
             investigator.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <gender_based>Yes</gender_based>
    <gender_description>Only femal can be included in breast cancer on the combination study.</gender_description>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Binghe Xu, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Chinese Academy of Medical Sciences and Peking Union Medical Colledge</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Fei Ma, MD</last_name>
    <phone>+86 13910217780</phone>
    <email>maifei2011@139.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>Chinese Academy of Medical Sciences and Peking Union Medical Colledge</name>
      <address>
        <city>Beijing</city>
        <state>Beijing</state>
        <zip>100021</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Fei Ma</last_name>
      <phone>+86 13910217780</phone>
      <email>maifei2011@139.com</email>
    </contact>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>April 2022</verification_date>
  <study_first_submitted>June 9, 2020</study_first_submitted>
  <study_first_submitted_qc>June 15, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 16, 2020</study_first_posted>
  <last_update_submitted>December 6, 2022</last_update_submitted>
  <last_update_submitted_qc>December 6, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">December 7, 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>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Tamoxifen</mesh_term>
  </intervention_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/NCT04433494
org study id: TYKM1602101
nct id: NCT04433494
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The primary objective of this study is to evaluate the safety and tolerability of TY-302
      single and the combination with Tamoxifen in dose-escalation and dose-expansion study.The
      drugs involved in this study are:

        -  TY-302

        -  Tamoxifen
This is an open-label, single-arm, phase I trial. The purpose of this study is to :

        -  Test a safe and tolerable dose of TY-302 single and the combination with Tamoxifen

        -  Determine the response rate of the combination

        -  Further evaluate the safety and side effect profile for the combination of TY-302 and
           Tamoxifen.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D) of TY-302
time frame: 1 year
description: To determine the MTD and RP2D of TY-302 in subjects with solid tumors
measure: Dose Limiting Toxicity (DLT) of TY-302
time frame: First 35 days of dosing
description: Incidence of Dose Limiting Toxicity (DLT) of TY-302
measure: Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D) of TY-302 combine with Tamoxifen
time frame: 1 year
description: To determine the MTD and RP2D of TY-302 and Tamoxifen on the combination in subjects with breast cancer
measure: Dose Limiting Toxicity (DLT) of TY-302 combine with Tamoxifen
time frame: First 28 days of dosing
description: Incidence of Dose Limiting Toxicity (DLT) of TY-302 and Tamoxifen on the combination
measure: Overall Response Rate (ORR) of TY-302 combine with Tamoxifen
time frame: 6 months
description: To assess the effect of TY-302 combine with Tamoxifen on ORR( the proportion of patients with a best overall response of complete response (CR) or partial response (PR) assessment in accordance to Response Evaluation Criteria in Solid Tumors (RECIST 1.1) ) in the treatment of ER+/HER2- advanced breast cancer.
measure: Disease Control Rate(DCR) of TY-302 combine with Tamoxifen
time frame: 9 months
description: To assess the effect of TY-302 combine with Tamoxifen on DCR(the proportion of patients with CR, PR, or stable disease(SD) assessment in accordance to RECIST 1.1) in the treatment of ER+/HER2- advanced breast cancer.
measure: Duration of Response (DOR) of TY-302 combine with Tamoxifen
time frame: 9 months
description: To assess the effect of TY-302 combine with Tamoxifen on DOR( the time from first documented response (PR or CR) to the date of first documented disease progression or death due to any cause determined by Investigator assessment in accordance to RECIST 1.1) in the treatment of ER+/HER2- advanced breast cancer.
measure: Progression-free Survival (PFS) of TY-302 combine with Tamoxifen
time frame: 12 months
description: To assess the effect of TY-302 combine with Tamoxifen on PFS(time from date of first dose of study treatment to date of first documented disease progression or death due to any cause determined by Investigator assessment in accordance to RECIST 1.1) in the treatment of ER+/HER2- advanced breast cancer.
arm group label: TY-302 ; TY-302 combine with Tamoxifen
arm group type: Experimental
description: TY-302
Find the maximum tolerated dose(MTD) and the recommended phase 2 dose (RP2D) of TY-302, given orally.
Increased dose cohorts from low dose to MTD, starting at 25mg daily.
TY-302 combine withTamoxifen in dose-escalation stage
TY-302: RP2D-1to RP2D daily for 28 days of each 28 day cycle.
Tamoxifen: 20mg twice daily for 28 days of each 28 day cycle.
TY-302 combine withTamoxifen in dose-expansion stage
TY-302: RP2D daily for 28 days of each 28 day cycle.
Tamoxifen: 20mg twice daily for 28 days of each 28 day cycle.
intervention type: Drug
intervention name: TY-302: capsule, 25mg/50mg ; Tamoxifen: tablet,10mg
description: TY-302 is taken orally. Tamoxifen is taken orally.
arm group label: TY-302 ; TY-302 combine with Tamoxifen
other name: TY-302
other name: Tamoxifen Citrate
criteria: 
gender: All
gender based: Yes
gender description: Only femal can be included in breast cancer on the combination study.
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Binghe Xu, MD
role: Principal Investigator
affiliation: Chinese Academy of Medical Sciences and Peking Union Medical Colledge
last name: Fei Ma, MD
phone: +86 13910217780
email: maifei2011@139.com
facility: 
status: Recruiting
contact: 
country: China
responsible party type: Sponsor
mesh term: Neoplasms
mesh term: Tamoxifen