xml: <clinical_study>
    <!-- This xml conforms to an XML Schema at:
      https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
    <required_header>
      <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
      <link_text>Link to the current ClinicalTrials.gov record.</link_text>
      <url>https://clinicaltrials.gov/ct2/show/NCT06031558</url>
    </required_header>
    <id_info>
      <org_study_id>SY-5007-III-01</org_study_id>
      <nct_id>NCT06031558</nct_id>
    </id_info>
    <brief_title>Phase III Study of SY-5007, a RET Inhibitor, in Patients With Locally Advanced or Metastatic RET Fusion-positive NSCLC</brief_title>
    <official_title>A Phase III, Open-Label, Single-arm, Multicenter Study to Evaluate the Efficacy and Safety of SY-5007, a RET Inhibitor, in Patients With Locally Advanced or Metastatic RET Fusion-positive NSCLC.</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Shouyao Holdings (Beijing) Co. LTD</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Shouyao Holdings (Beijing) Co. LTD</source>
    <oversight_info>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        This is a phase III, open-label, single-arm, multicenter study designed to evaluate the&#xD;
        anti-tumor activity and safety of SY-5007 administered orally to participants with locally&#xD;
        advanced or metastatic RET-positive NSCLC.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        This study will enroll patients with locally advanced or metastatic RET-positive NSCLC.&#xD;
        SY-5007 will be administered orally 160 mg twice daily in 28-day cycle continuously until&#xD;
        disease progression, death, unacceptable toxicity, withdrawal of consent, or&#xD;
        protocol-specified parameters. This study is designed to evaluate the antitumor activity&#xD;
        (ORR, DCR, DOR, PFS and OS) and safety of SY-5007 in patients.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Recruiting</overall_status>
    <start_date type="Actual">June 20, 2023</start_date>
    <completion_date type="Anticipated">June 20, 2026</completion_date>
    <primary_completion_date type="Anticipated">September 20, 2024</primary_completion_date>
    <phase>Phase 3</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>Single Group Assignment</intervention_model_description>
      <primary_purpose>Treatment</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Assessment of overall response rate (ORR) by independent review committee (IRC).</measure>
      <time_frame>Tumor scans performed at baseline then every 8 weeks up to 1 year, then every 12 weeks thereafter; up to 3 years.</time_frame>
      <description>Defined as the number (%) of patients with measurable disease with response of CR or PR assessed by IRC according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>ORR as assessed by investigators.</measure>
      <time_frame>Up to 3 years.</time_frame>
      <description>Defined as the number (%) of patients with measurable disease with response of CR or PR assessed by investigators according to RECIST version 1.1.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Disease control rate (DCR) as assessed by investigators and IRC.</measure>
      <time_frame>Up to 3 years.</time_frame>
      <description>Defined as the number (%) of patients who have a best overall response of CR or PR or SD according to RECIST 1.1.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Progression free survival (PFS) as assessed by investigators and IRC.</measure>
      <time_frame>Up to 3 years.</time_frame>
      <description>PFS is defined as the time from the date of randomization to progression of tumor as assessed by investigators or death from any cause on study.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Time to response (TTR) as assessed by investigators and IRC.</measure>
      <time_frame>Up to 3 years.</time_frame>
      <description>TTR is defined as the time from the date of randomization to the first response of CR or PR.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Duration of response (DoR) as assessed by investigators and IRC.</measure>
      <time_frame>Up to 3 years.</time_frame>
      <description>DoR is defined as the time from first response until disease progression or death, whichever occurs first.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Overall survival (OS).</measure>
      <time_frame>Up to 3 years.</time_frame>
      <description>OS is defined as the time from the date of randomization until death due to any cause.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Incidence of adverse events (AEs) and serious adverse events (SAEs).</measure>
      <time_frame>From the screening period to 28 days after treatment completion, up to a maximum of approximately 3 years.</time_frame>
      <description>AEs are graded according to CTCAE v 5.0.</description>
    </secondary_outcome>
    <number_of_arms>1</number_of_arms>
    <enrollment type="Anticipated">120</enrollment>
    <condition>Non-Small Cell Lung Cancer</condition>
    <arm_group>
      <arm_group_label>SY-5007</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>SY-5007 will be given orally 160 mg twice daily in 28-day cycle continuously until disease progression, death, unacceptable toxicity, or withdraw consent in this study.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>SY-5007</intervention_name>
      <description>a RET selective Inhibitor</description>
      <arm_group_label>SY-5007</arm_group_label>
      <other_name>SY-5007 Tabletes</other_name>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. Male or female, at least 18 years old.&#xD;
  &#xD;
            2. Histologically or cytologically confirmed diagnosis of locally advanced (with a tumor&#xD;
               lesion that cannot be eradicated by surgery or radiotherapy as assessed by the&#xD;
               investigators) or metastatic NSCLC.&#xD;
  &#xD;
            3. No prior systemic antitumor therapy for locally advanced or metastatic NSCLC (Note:&#xD;
               enrollment is permitted in the following 2 situations: 1) received only adjuvant&#xD;
               therapy and the end of treatment was ≥ 6 months prior to the first dose; 2) received&#xD;
               only radical radiotherapy and the end of treatment was ≥ 6 months prior to the first&#xD;
               dose).&#xD;
  &#xD;
            4. The patient's tumor tissue or blood sample test result meets 1 of the following two&#xD;
               criteria: a. Previous tumor tissue or blood samples are confirmed as RET fusion&#xD;
               positive by local laboratory testing. b. If there is no previous RET fusion positive&#xD;
               test report, a compliant tumor tissue or blood sample is required to be provided at&#xD;
               the central laboratory, using a next-generation sequencing (NGS)-based assay to&#xD;
               confirm RET fusion positive.&#xD;
  &#xD;
            5. Patients have at least one measurable lesion per RECIST version 1.1. (except for&#xD;
               patients with measurable lesions in the brain only) (Note: a lesion that has been&#xD;
               treated with radiotherapy or localized therapy is generally not considered a&#xD;
               measurable lesion unless there is definitive progression of that lesion).&#xD;
  &#xD;
            6. Eastern Cooperative Oncology Group (ECOG) performance status score of 0 to 1;&#xD;
  &#xD;
            7. Life expectancy of at least 3 months.&#xD;
  &#xD;
            8. Patients must have adequate organ function as defined in the below:&#xD;
  &#xD;
               Bone marrow function:&#xD;
  &#xD;
               patients must not have received any blood products, hematopoietic cell growth factors&#xD;
               or other blood medications for at least 7 days prior to the first dose, and have a&#xD;
               blood count: absolute neutrophil count (ANC) ≥ 1.5 x 10^9 /L, platelet (PLT) count ≥&#xD;
               75 x 10^9 /L, and hemoglobin (Hb) ≥ 90 g/L;&#xD;
  &#xD;
               Liver function:&#xD;
  &#xD;
               total bilirubin (TBIL) ≤ 1.5 times upper limit of normal (ULN) and both aspartate&#xD;
               aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 times ULN in the&#xD;
               absence of liver metastases; in the presence of liver metastases, both AST and ALT ≤&#xD;
               5.0 times ULN and TBIL ≤ 3 times ULN;&#xD;
  &#xD;
               Renal function:&#xD;
  &#xD;
               creatinine clearance (Ccr) ≥ 50 mL/min.&#xD;
  &#xD;
               Coagulation function:&#xD;
  &#xD;
               prothrombin time (PT) or International Normalized Ratio (INR) ≤ 1.5 times ULN.&#xD;
  &#xD;
            9. Patients can swallow the drug orally and are able to comply with follow-up visit&#xD;
               requirements.&#xD;
  &#xD;
           10. Male and female patients of childbearing potential must be willing to abstain&#xD;
               completely or agree to use an appropriate method of contraception for the duration of&#xD;
               the study and for at least 3 months after the last dose of study medication.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. Patients carried known major driver genetic alterations other than RET. e.g. EGFR,&#xD;
               MET, ALK, ROS1, NTRK, BRAF V600, KRAS G12C, etc. (If a patient has a co-mutation,&#xD;
               discuss with the investigators whether enrollment is possible).&#xD;
  &#xD;
            2. History of allergy to any components or excipients of SY-5007 tablets.&#xD;
  &#xD;
            3. Patients with malignancies other than NSCLC treated in this study (except:&#xD;
               malignancies that are cured and have not recurred within 2 years prior to study entry;&#xD;
               completely resected basal cell and squamous cell skin cancer; completely resected&#xD;
               carcinoma in situ of the cervix or breast).&#xD;
  &#xD;
            4. Patient has clinically symptomatic primary central nervous system (CNS) tumor,&#xD;
               symptomatic CNS metastases, molluscum contagiosum, or untreated spinal cord&#xD;
               compression; exclusion: patient has stable CNS disease (no evidence of progression as&#xD;
               determined by imaging for at least 4 weeks prior to the first dose and all&#xD;
               neurological symptoms have returned to baseline levels), no evidence of new or&#xD;
               enlarging brain metastases, and has not had CNS surgery or radiotherapy within 4 weeks&#xD;
               prior to the first dose, has not undergone stereotactic radiosurgery within 2 weeks,&#xD;
               and has discontinued or stablized steroid dosing within 2 weeks.&#xD;
  &#xD;
            5. Comorbidities of the following symptoms or conditions prior to the first dose that&#xD;
               remain poorly controlled with optimal therapy:&#xD;
  &#xD;
               active uncontrolled systemic bacterial, viral, or fungal infections; pleural,&#xD;
               abdominal, or pericardial effusions that are poorly controlled with interventions&#xD;
               (e.g., drainage) (poorly controlled is defined as growth that is significant and&#xD;
               symptomatic within 2 weeks of fluid collection and requires re-puncturing or other&#xD;
               interventions); poorly controlled diabetes mellitus [fasting blood glucose ≥ 10 mmol/L&#xD;
               and/or glycated hemoglobin (HbA1c) ≥ 8%]; uncontrolled symptomatic hyperthyroidism or&#xD;
               hypothyroidism as assessed by the investigators; uncontrolled electrolyte disorders&#xD;
               (e.g., hyper/hypocalcemia, hyper/hypomagnesemia, hyper/hypokalemia) as assessed by the&#xD;
               investigators; clinically significant severe gastrointestinal disorders as assessed by&#xD;
               the investigators, including active ulcerative colitis Crohn's disease, peptic ulcers,&#xD;
               or previous surgical procedures that may have significantly interfered with the&#xD;
               absorption of the drug.&#xD;
  &#xD;
            6. Presence of serious cardiovascular disease/abnormalities as indicated by any of the&#xD;
               following:&#xD;
  &#xD;
               a QTcF &gt; 470 msec (females) or &gt; 450 msec (males) using the Fridericia formula for&#xD;
               heart rate correction at screening, (If drug-induced prolongation of the QTcF is&#xD;
               suspected, it is assessed by the investigators to be safe and manageable and may be&#xD;
               corrected with medication and then enrolled.); left ventricular ejection fraction&#xD;
               (LVEF) &lt; 45%; myocardial infarction or unstable angina pectoris or clinically&#xD;
               significant uncontrolled arrhythmia within 6 months prior to the first dose of the&#xD;
               drug, including bradyarrhythmias (e.g., type II second or third-degree heart block)&#xD;
               that may result in prolongation of the QTcF; classified as class III or IV according&#xD;
               to New York Heart Association (NYHA) criteria Congestive heart failure; poorly&#xD;
               controlled hypertension (systolic blood pressure &gt;150 mmHg or diastolic blood pressure&#xD;
               &gt;100 mmHg), history of unstable hypertension, or history of poor compliance with&#xD;
               antihypertensive therapy.&#xD;
  &#xD;
            7. Presence of active viral infection or history of:&#xD;
  &#xD;
               Hepatitis B (Hepatitis B surface antigen [HBsAg] positive with HBV DNA test &gt; 2 x 10^3&#xD;
               IU/mL, eligible for enrollment if re-tested to less than 2 x 10^3 IU/mL with regular&#xD;
               antiviral therapy); positive test for Human Immunodeficiency Virus (HIV) at screening&#xD;
               or a known history of other immune deficient disorders; a history of prior organ&#xD;
               transplantation, hematopoietic stem cell or bone marrow transplantation therapy.&#xD;
  &#xD;
            8. Presence of other lung diseases that require systemic treatment or are serious, such&#xD;
               as active tuberculosis, interstitial lung disease, etc., which in the opinion of the&#xD;
               investigators may influence the interpretation of the study results or put the patient&#xD;
               at high risk.&#xD;
  &#xD;
            9. Patients who had used or were unable to discontinue the following potent inhibitors or&#xD;
               inducers of CYP3A4 during the study period within 2 weeks prior to the first dose.&#xD;
               CYP3A4 potent inhibitors: atazanavir, clarithromycin, indinavir, itraconazole,&#xD;
               ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin,&#xD;
               vinpocetine, voriconazole; and CYP3A4 potent inducers: carbamazepine, phenobarbital,&#xD;
               phenytoin, rifabutin, rifampin.&#xD;
  &#xD;
           10. Palliative radiotherapy within 1 week prior to the first dose, or any lung&#xD;
               radiotherapy with more than 30 Gy of radiation within 6 months prior to the first&#xD;
               dose.&#xD;
  &#xD;
           11. Major surgical procedure (except central venous catheterization, tumor puncture&#xD;
               biopsy, and gastric tube placement) or significant trauma within 4 weeks prior to the&#xD;
               first dose.&#xD;
  &#xD;
           12. Participation in another clinical trial within 4 weeks prior to the first dose (note:&#xD;
               except for those who are not using the investigational drug or investigational medical&#xD;
               device; or those who have discontinued treatment from another clinical trial and are&#xD;
               only being followed for subsequent survival) or are planning to participate in another&#xD;
               clinical trial during the study period.&#xD;
  &#xD;
           13. Serious arterial/venous thrombotic event within 1 year prior to the first dose, such&#xD;
               as cerebrovascular accident, deep vein thrombosis, pulmonary embolism, or bleeding&#xD;
               tendency within 30 days prior to the first dose, or risk of gastrointestinal bleeding&#xD;
               as judged by the investigators.&#xD;
  &#xD;
           14. Female patients who are pregnant or breastfeeding.&#xD;
  &#xD;
           15. Any other conditions that, in the opinion of the investigators, makes participation in&#xD;
               this clinical trial inappropriate.&#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>Yinghui Sun, PhD</last_name>
      <role>Study Director</role>
      <affiliation>Shouyao Holdings (Beijing) Co. LTD</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Yinghui Sun, PhD</last_name>
      <phone>86-10-88858616</phone>
      <email>yhsun@centaurusbio.com</email>
    </overall_contact>
    <location>
      <facility>
        <name>Shanghai Pulmonary Hospital</name>
        <address>
          <city>Shanghai</city>
          <state>Shanghai</state>
          <zip>200433</zip>
          <country>China</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Caicun Zhou, PhD</last_name>
        <phone>13301825532</phone>
        <email>caicunzhoudr@163.com</email>
      </contact>
      <investigator>
        <last_name>Caicun Zhou, phD</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location_countries>
      <country>China</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 31, 2023</study_first_submitted>
    <study_first_submitted_qc>September 4, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">September 11, 2023</study_first_posted>
    <last_update_submitted>September 4, 2023</last_update_submitted>
    <last_update_submitted_qc>September 4, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 11, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>SY-5007</keyword>
    <keyword>RET-positive NSCLC</keyword>
    <keyword>Locally advanced RET-positive NSCLC</keyword>
    <keyword>Metastatic RET-positive NSCLC</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Carcinoma, Non-Small-Cell Lung</mesh_term>
    </condition_browse>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: download date: ClinicalTrials.gov processed this data on September 20, 2023
  link text: Link to the current ClinicalTrials.gov record.
  url: https://clinicaltrials.gov/ct2/show/NCT06031558
  org study id: SY-5007-III-01
  nct id: NCT06031558
  lead sponsor: 
  is fda regulated drug: No
  is fda regulated device: No
  This is a phase III, open-label, single-arm, multicenter study designed to evaluate the
        anti-tumor activity and safety of SY-5007 administered orally to participants with locally
        advanced or metastatic RET-positive NSCLC.
  This study will enroll patients with locally advanced or metastatic RET-positive NSCLC.
        SY-5007 will be administered orally 160 mg twice daily in 28-day cycle continuously until
        disease progression, death, unacceptable toxicity, withdrawal of consent, or
        protocol-specified parameters. This study is designed to evaluate the antitumor activity
        (ORR, DCR, DOR, PFS and OS) and safety of SY-5007 in patients.
  allocation: N/A
  intervention model: Single Group Assignment
  intervention model description: Single Group Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Assessment of overall response rate (ORR) by independent review committee (IRC).
  time frame: Tumor scans performed at baseline then every 8 weeks up to 1 year, then every 12 weeks thereafter; up to 3 years.
  description: Defined as the number (%) of patients with measurable disease with response of CR or PR assessed by IRC according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
  measure: ORR as assessed by investigators.
  time frame: Up to 3 years.
  description: Defined as the number (%) of patients with measurable disease with response of CR or PR assessed by investigators according to RECIST version 1.1.
  measure: Disease control rate (DCR) as assessed by investigators and IRC.
  time frame: Up to 3 years.
  description: Defined as the number (%) of patients who have a best overall response of CR or PR or SD according to RECIST 1.1.
  measure: Progression free survival (PFS) as assessed by investigators and IRC.
  time frame: Up to 3 years.
  description: PFS is defined as the time from the date of randomization to progression of tumor as assessed by investigators or death from any cause on study.
  measure: Time to response (TTR) as assessed by investigators and IRC.
  time frame: Up to 3 years.
  description: TTR is defined as the time from the date of randomization to the first response of CR or PR.
  measure: Duration of response (DoR) as assessed by investigators and IRC.
  time frame: Up to 3 years.
  description: DoR is defined as the time from first response until disease progression or death, whichever occurs first.
  measure: Overall survival (OS).
  time frame: Up to 3 years.
  description: OS is defined as the time from the date of randomization until death due to any cause.
  measure: Incidence of adverse events (AEs) and serious adverse events (SAEs).
  time frame: From the screening period to 28 days after treatment completion, up to a maximum of approximately 3 years.
  description: AEs are graded according to CTCAE v 5.0.
  arm group label: SY-5007
  arm group type: Experimental
  description: SY-5007 will be given orally 160 mg twice daily in 28-day cycle continuously until disease progression, death, unacceptable toxicity, or withdraw consent in this study.
  intervention type: Drug
  intervention name: SY-5007
  description: a RET selective Inhibitor
  arm group label: SY-5007
  other name: SY-5007 Tabletes
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Yinghui Sun, PhD
  role: Study Director
  affiliation: Shouyao Holdings (Beijing) Co. LTD
  last name: Yinghui Sun, PhD
  phone: 86-10-88858616
  email: yhsun@centaurusbio.com
  facility: 
  status: Recruiting
  contact: 
  investigator: 
  country: China
  responsible party type: Sponsor
  mesh term: Carcinoma, Non-Small-Cell Lung