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/NCT06006793</url>
    </required_header>
    <id_info>
      <org_study_id>SY-5933-I-01</org_study_id>
      <nct_id>NCT06006793</nct_id>
    </id_info>
    <brief_title>A Study of SY-5933 in Patients With Advanced Solid Tumors Harboring the KRAS p.G12C Mutation</brief_title>
    <official_title>A Phase I, Dose-escalation/Dose-expansion Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Anti-Tumor Activity of SY-5933 Tablets in Patients With Advanced KRAS p.G12C Mutant Solid Tumors</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 single-arm, open-label, phase 1 study to evaluate the safety, tolerability,&#xD;
        pharmacokinetics (PK), and anti-tumor activity of SY-5933 in patients with KRAS p.G12C mutant&#xD;
        advanced solid tumors.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        The study will be conducted in 2 parts: Part 1 - Dose Escalation and Part 2 - Dose Expansion.&#xD;
        Part 1 is aimed at evaluating the safety, tolerability, PK and pharmacodynamics of SY-5933&#xD;
        and determining the recommended phase II dose (RP2D) of repeat daily (QD) dosing schedule in&#xD;
        subjects with advanced KRAS p.G12C mutant solid tumors using accelerated titration and 3+3&#xD;
        design. The dose escalation part of the study will consist of 7-13 subjects and the dose&#xD;
        expansion part will consist of 30-60 additional subjects, comprising 2 cohorts. Cohort A&#xD;
        includes patients with non-small cell lung cancer (NSCLC) harboring KRAS p.G12C mutations and&#xD;
        Cohort B includes patients with other advanced solid tumors (colorectal, pancreatic cancers,&#xD;
        etc.). Patients in dose expansion study will receive SY-5933 tablets QD, oral administration,&#xD;
        28 days as a dosing cycle, to further evaluate the safety, PK profile, and efficacy of&#xD;
        SY-5933, and to further define RP2D. Administration of SY-5933 may continue until evidence of&#xD;
        disease progression, intolerance to SY-5933, or withdrawal of consent.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Recruiting</overall_status>
    <start_date type="Actual">August 10, 2023</start_date>
    <completion_date type="Anticipated">August 15, 2025</completion_date>
    <primary_completion_date type="Anticipated">February 15, 2025</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>Incidence of Dose-limiting toxicities (DLTs)</measure>
      <time_frame>31 days after the first dose (single dose for 3 days and dose-escalation cycle 1 for 28 days)</time_frame>
      <description>Number of participants with DLTs</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Number of participants with adverse events</measure>
      <time_frame>Up to 18 months</time_frame>
      <description>Patients will be assessed for incidence and severity of adverse events (AEs) according to NCI-CTCAE v5.0 criteria</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Pharmacokinetics (Cmax) for SY-5933</measure>
      <time_frame>Protocol-defined time points during 3 days after the first dose and cycle 1 (each cycle is 28 days)</time_frame>
      <description>Defined as maximum observed plasma concentration</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Pharmacokinetics (Tmax) for SY-5933</measure>
      <time_frame>Protocol-defined time points during 3 days after the first dose and cycle 1 (each cycle is 28 days)</time_frame>
      <description>Defined as time to maximum plasma concentration</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Pharmacokinetics (AUC0-t) for SY-5933</measure>
      <time_frame>Protocol-defined time points during 3 days after the first dose and cycle 1 (each cycle is 28 days)</time_frame>
      <description>Defined as area under the single-dose plasma concentration-time curve from Hour 0 to the last quantifiable measurable plasma concentration</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Pharmacokinetics (t½) for SY-5933</measure>
      <time_frame>Protocol-defined time points during 3 days after the first dose and cycle 1 (each cycle is 28 days)</time_frame>
      <description>Defined as the apparent plasma terminal phase disposition half-life</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Overall Response Rate (ORR) as assessed by RECIST 1.1 criteria</measure>
      <time_frame>Up to 24 months</time_frame>
      <description>Preliminary measure of anti-tumor activity of SY-5933 in patients with KRAS p.G12C mutant advanced tumor</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Disease control rate (DCR) as assessed by RECIST 1.1 criteria</measure>
      <time_frame>Up to 24 months</time_frame>
      <description>Preliminary measure of anti-tumor activity of SY-5933 in patients with KRAS p.G12C mutant advanced tumor</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Duration of response (DOR)</measure>
      <time_frame>Up to 24 months</time_frame>
      <description>Preliminary measure of anti-tumor activity of SY-5933 in patients with KRAS p.G12C mutant advanced tumor</description>
    </secondary_outcome>
    <number_of_arms>1</number_of_arms>
    <enrollment type="Anticipated">50</enrollment>
    <condition>Advanced Solid Tumor</condition>
    <arm_group>
      <arm_group_label>Dose-escalation and Dose-expansion</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>In dose-escalation phase, SY-5933 tablets will be administrated orally, repeat daily, 28 days as a dosing cycle, in ascending doses.&#xD;
  In dose-expansion phase, RP2D of SY-5933 determined in dose-escalation phase will be administrated orally, repeat daily, 28 days as a dosing cycle.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>SY-5933</intervention_name>
      <description>KRAS p.G12C inhibitor</description>
      <arm_group_label>Dose-escalation and Dose-expansion</arm_group_label>
      <other_name>SY-5933 tablet</other_name>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. Men or women ≥ 18 years old&#xD;
  &#xD;
            2. Eastern Collaboration Oncology Group (ECOG) performance status (PS) scored of 0-1.&#xD;
  &#xD;
            3. Estimated life expectancy &gt;12 weeks.&#xD;
  &#xD;
            4. Patients must have at least one assessable lesion in the dose-escalation part and one&#xD;
               measurable lesion in the dose-expansion part per Response Evaluation Criteria in Solid&#xD;
               Tumors (RECIST) version 1.1.&#xD;
  &#xD;
            5. In the dose-escalation part, patients must have histologically or cytologically&#xD;
               confirmed advanced solid tumors harboring the KRAS p.G12C mutation and have progressed&#xD;
               after standard therapy, or standard therapy is inappropriate or unavailable.&#xD;
  &#xD;
               In the dose-expansion part, patients must have histologically or cytologically&#xD;
               confirmed advanced KRAS p.G12C mutant NSCLCs (cohort A) and CRCs, PDACs, and other&#xD;
               solid tumors (Cohort B) and have progressed after standard therapy, or standard&#xD;
               therapy is inappropriate or unavailable.&#xD;
  &#xD;
            6. Adequate organ function as defined in the below:&#xD;
  &#xD;
               Hepatic function Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3 times&#xD;
               upper limit of normal (ULN), or ≤ 5 times ULN in the presence of liver metastases.&#xD;
               Total serum bilirubin (TBIL) ≤ 1.5 times ULN; TBIL≤3×ULN and direct&#xD;
               bilirubin（DBIL）≤1.5×ULN in the presence of liver metastases or with Gilbert's&#xD;
               syndrome.&#xD;
  &#xD;
               Bone marrow function No blood transfusion or hematopoietic stimulator treatment within&#xD;
               7 days; absolute neutrophil count (ANC) ≥1.5×10^9/L; platelets (PLT) count ≥75×10^9/L;&#xD;
               hemoglobin (Hb) ≥ 90 g/L.&#xD;
  &#xD;
               Renal function Creatinine clearance ≥ 50 mL/min. Coagulation function International&#xD;
               normalized ratio (INR) or prothrombin time (PT) ≤ 1.5 times ULN.&#xD;
  &#xD;
            7. Female patients with reproductive potential must have a negative serum pregnancy test&#xD;
               within 7 days prior to the first dose. Both male and female patients of reproductive&#xD;
               potential must be willing to abstain completely or agree to use an appropriate method&#xD;
               of contraception during the entire study duration and for at least 3 months after the&#xD;
               last dose of study medication.&#xD;
  &#xD;
            8. Willingness and ability to give informed consent and follow protocol procedures, and&#xD;
               comply with follow-up visit requirements.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. Dose-escalation phase: patients with known driver alterations other than KRAS p.G12C,&#xD;
               e.g., EGFR, ALK, ROS1, RET, TRK, etc. (Enrollment of patients with co-mutations may be&#xD;
               discussed with the investigator).&#xD;
  &#xD;
            2. Dose-expansion phase: prior use of selective KRAS inhibitors.&#xD;
  &#xD;
            3. Patients who received chemotherapy, radiotherapy, biological therapy, endocrine&#xD;
               therapy, immunotherapy, and other anti-tumor treatment within 3 weeks before the first&#xD;
               administration, except for the following: Nitrosourea or mitomycin C was received&#xD;
               within 6 weeks before the first administration; Oral fluoropyrimidines and small&#xD;
               molecule targeted drugs within 2 weeks or 5 half-lives of the drug (whichever is&#xD;
               longer) prior to the first administration; Chinese proprietary medicines with&#xD;
               anti-tumor indications were received within 2 weeks before the first administration.&#xD;
  &#xD;
            4. Received other unapproved investigational drugs or treatments within 4 weeks prior to&#xD;
               the first administration.&#xD;
  &#xD;
            5. Have undergone major organ surgery (excluding needle biopsy) or had significant trauma&#xD;
               within 4 weeks prior to the first administration.&#xD;
  &#xD;
            6. Unresolved toxicities from prior anti-tumor therapy, defined as not having resolved to&#xD;
               Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 grade ≤&#xD;
               1(exceptions for toxicities judged by the investigator to be of no safety concern,&#xD;
               e.g. alopecia, grade 2 peripheral neurotoxicity, etc.).&#xD;
  &#xD;
            7. Presence of spinal cord compression, meningeal metastases, clinically symptomatic&#xD;
               brain metastases, or need for increased steroid doses to control central nervous&#xD;
               system (CNS) disease; patients with symptomatic CNS metastases that are already under&#xD;
               control may be eligible for this study.&#xD;
  &#xD;
            8. Patients with active infection who need systematic anti-infective therapy within 2&#xD;
               weeks prior to the first administration.&#xD;
  &#xD;
            9. Active hepatitis (Hepatitis B: Hepatitis B virus surface antigen [HBsAg] positive with&#xD;
               HBV DNA ≥2000 IU/mL; Hepatitis C: Hepatitis C virus antibody positive with HCV RNA&#xD;
               ≥1000 IU/mL), HIV antibody positive, active syphilis (double positive for syphilis&#xD;
               non-specific and syphilis specific antibodies) that is uncontrolled by treatment and&#xD;
               inappropriate for enrollment as determined by the investigator.&#xD;
  &#xD;
           10. Presence of other lung diseases requiring systemic treatment or severe lung diseases&#xD;
               such as active tuberculosis, interstitial lung disease, etc., which in the opinion of&#xD;
               the investigator may affect the interpretation of the study results or place the&#xD;
               patient at high risk;&#xD;
  &#xD;
           11. A history of serious cardiovascular and cerebrovascular disease, including but not&#xD;
               limited to severe cardiac rhythm and conduction abnormalities, such as ventricular&#xD;
               arrhythmias and degree II-III atrioventricular block requiring clinical intervention;&#xD;
               Longer QT interval at rest (QTc &gt; 470 msec for women or &gt; 450 msec for men); Acute&#xD;
               coronary syndrome, congestive heart failure, aortic dissection, stroke, or other grade&#xD;
               3 or higher cardiovascular and cerebrovascular events occurred within 6 months prior&#xD;
               to first administration; Heart failure with the New York Heart Association (NYHA)&#xD;
               Heart function rating ≥ II or left ventricular ejection fraction (LVEF) &lt; 50%;&#xD;
               Clinically uncontrolled hypertension.&#xD;
  &#xD;
           12. Strong inhibitor or inducer of CYP3A, P-glycoprotein inducer or inhibitor used within&#xD;
               1 week or 5 half-lives (whichever is longer) prior to the first administration or&#xD;
               expected to be used during the study period.&#xD;
  &#xD;
           13. Patients with malignancies other than tumors treated in this study (except&#xD;
               malignancies that are cured and have not recurred within 2 years prior to study&#xD;
               enrollment; completely resected basal cell and squamous cell skin cancer; completely&#xD;
               resected carcinoma in situ of any type).&#xD;
  &#xD;
           14. Severe gastrointestinal disease of clinical significance as determined by the&#xD;
               investigator, including active ulcerative colitis, Crohn's disease, peptic ulcer&#xD;
               disease, or previous surgical procedures that may have significantly affected drug&#xD;
               absorption.&#xD;
  &#xD;
           15. History of allergy to study drug components or adjuvants.&#xD;
  &#xD;
           16. Pleural, abdominal, or pericardial effusions that are poorly controlled despite&#xD;
               intervention (defined as effusion that has grown significantly within 2 weeks of&#xD;
               removal and is symptomatic requiring re-puncture or other intervention).&#xD;
  &#xD;
           17. Uncontrolled diabetes mellitus [fasting blood glucose ≥10 mmol/L and/or glycated&#xD;
               hemoglobin (HbA1c) ≥8%], uncontrolled symptomatic hyperthyroidism or hypothyroidism,&#xD;
               uncontrolled symptomatic hypercalcemia or hypocalcemia.&#xD;
  &#xD;
           18. Have a coagulation disorder or bleeding tendency, including an arterial or venous&#xD;
               thromboembolic event or any life-threatening bleeding event within 6 months prior to&#xD;
               first administration, or have a lesion involving a major blood vessel, or have a&#xD;
               bleeding tendency as determined by the investigator.&#xD;
  &#xD;
           19. Pregnant or lactating women.&#xD;
  &#xD;
           20. Presence of any condition that may increase the risks associated with the&#xD;
               administration of the study drug or that may affect the interpretation of the study&#xD;
               results, or poor patient compliance, or any other condition that, in the opinion of&#xD;
               the investigator, makes the enrollment inappropriate.&#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_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>
          <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>
    </location>
    <location_countries>
      <country>China</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 10, 2023</study_first_submitted>
    <study_first_submitted_qc>August 16, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 23, 2023</study_first_posted>
    <last_update_submitted>August 29, 2023</last_update_submitted>
    <last_update_submitted_qc>August 29, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 1, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>KRAS p.G12C Mutation</keyword>
    <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>
  
  
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/NCT06006793
  org study id: SY-5933-I-01
  nct id: NCT06006793
  lead sponsor: 
  is fda regulated drug: No
  is fda regulated device: No
  This is a single-arm, open-label, phase 1 study to evaluate the safety, tolerability,
        pharmacokinetics (PK), and anti-tumor activity of SY-5933 in patients with KRAS p.G12C mutant
        advanced solid tumors.
  The study will be conducted in 2 parts: Part 1 - Dose Escalation and Part 2 - Dose Expansion.
        Part 1 is aimed at evaluating the safety, tolerability, PK and pharmacodynamics of SY-5933
        and determining the recommended phase II dose (RP2D) of repeat daily (QD) dosing schedule in
        subjects with advanced KRAS p.G12C mutant solid tumors using accelerated titration and 3+3
        design. The dose escalation part of the study will consist of 7-13 subjects and the dose
        expansion part will consist of 30-60 additional subjects, comprising 2 cohorts. Cohort A
        includes patients with non-small cell lung cancer (NSCLC) harboring KRAS p.G12C mutations and
        Cohort B includes patients with other advanced solid tumors (colorectal, pancreatic cancers,
        etc.). Patients in dose expansion study will receive SY-5933 tablets QD, oral administration,
        28 days as a dosing cycle, to further evaluate the safety, PK profile, and efficacy of
        SY-5933, and to further define RP2D. Administration of SY-5933 may continue until evidence of
        disease progression, intolerance to SY-5933, or withdrawal of consent.
  allocation: N/A
  intervention model: Single Group Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Incidence of Dose-limiting toxicities (DLTs)
  time frame: 31 days after the first dose (single dose for 3 days and dose-escalation cycle 1 for 28 days)
  description: Number of participants with DLTs
  measure: Number of participants with adverse events
  time frame: Up to 18 months
  description: Patients will be assessed for incidence and severity of adverse events (AEs) according to NCI-CTCAE v5.0 criteria
  measure: Pharmacokinetics (Cmax) for SY-5933
  time frame: Protocol-defined time points during 3 days after the first dose and cycle 1 (each cycle is 28 days)
  description: Defined as maximum observed plasma concentration
  measure: Pharmacokinetics (Tmax) for SY-5933
  time frame: Protocol-defined time points during 3 days after the first dose and cycle 1 (each cycle is 28 days)
  description: Defined as time to maximum plasma concentration
  measure: Pharmacokinetics (AUC0-t) for SY-5933
  time frame: Protocol-defined time points during 3 days after the first dose and cycle 1 (each cycle is 28 days)
  description: Defined as area under the single-dose plasma concentration-time curve from Hour 0 to the last quantifiable measurable plasma concentration
  measure: Pharmacokinetics (t½) for SY-5933
  time frame: Protocol-defined time points during 3 days after the first dose and cycle 1 (each cycle is 28 days)
  description: Defined as the apparent plasma terminal phase disposition half-life
  measure: Overall Response Rate (ORR) as assessed by RECIST 1.1 criteria
  time frame: Up to 24 months
  description: Preliminary measure of anti-tumor activity of SY-5933 in patients with KRAS p.G12C mutant advanced tumor
  measure: Disease control rate (DCR) as assessed by RECIST 1.1 criteria
  time frame: Up to 24 months
  description: Preliminary measure of anti-tumor activity of SY-5933 in patients with KRAS p.G12C mutant advanced tumor
  measure: Duration of response (DOR)
  time frame: Up to 24 months
  description: Preliminary measure of anti-tumor activity of SY-5933 in patients with KRAS p.G12C mutant advanced tumor
  arm group label: Dose-escalation and Dose-expansion
  arm group type: Experimental
  description: In dose-escalation phase, SY-5933 tablets will be administrated orally, repeat daily, 28 days as a dosing cycle, in ascending doses.
  In dose-expansion phase, RP2D of SY-5933 determined in dose-escalation phase will be administrated orally, repeat daily, 28 days as a dosing cycle.
  intervention type: Drug
  intervention name: SY-5933
  description: KRAS p.G12C inhibitor
  arm group label: Dose-escalation and Dose-expansion
  other name: SY-5933 tablet
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 75 Years
  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: 
  country: China
  responsible party type: Sponsor
  mesh term: Neoplasms