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/NCT06041035</url>
    </required_header>
    <id_info>
      <org_study_id>QLS31905-201</org_study_id>
      <nct_id>NCT06041035</nct_id>
    </id_info>
    <brief_title>A Study of QLS31905 Combination Chemotherapy as First-Line Treatment in Patients With Advanced Solid Tumors</brief_title>
    <official_title>A Phase IB/II Clinical Study to Assess the Efficacy and Safety of QLS31905 in Combination With Chemotherapy as First-line Treatment in Patients With Claudin 18.2 (CLDN18.2) Positive Advanced Malignant Solid Tumors</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Qilu Pharmaceutical Co., Ltd.</agency>
        <agency_class>Industry</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Qilu Pharmaceutical Co., Ltd.</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>
        This study aims to evaluate the efficacy and safety of QLS31905 plus chemotherapy in patients&#xD;
        with Claudin18.2-positive advanced solid tumors.&#xD;
      </textblock>
    </brief_summary>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">October 2023</start_date>
    <completion_date type="Anticipated">October 2025</completion_date>
    <primary_completion_date type="Anticipated">October 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>Non-Randomized</allocation>
      <intervention_model>Parallel Assignment</intervention_model>
      <primary_purpose>Treatment</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Maximum Tolerated Dose (MTD) (Part A)</measure>
      <time_frame>Approximately 12 months</time_frame>
      <description>As measured by number of participants experiencing dose related toxicity (DLT) in each escalating cohort.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Phase 2 Recommended Dose（RP2D)(Part A)</measure>
      <time_frame>Approximately 12 months</time_frame>
      <description>Monitor for MTD, and minimal efficacious dose by monitoring responses at different dose levels.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Objective response rate (ORR)(Part B)</measure>
      <time_frame>Approximately 12 months</time_frame>
      <description>ORR is defined as the proportion of participants who have a best overall response of Complete Response (CR) or Partial Response (PR) as assessed by investigator evaluation per RECIST 1.1.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Safety assessed by Adverse Events (AEs)</measure>
      <time_frame>Approximately 12 months</time_frame>
      <description>An AE is any untoward medical occurrence in a subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom,or disease (new or exacerbated) temporally associated with the use of a medicinal product.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Safety assessed by incidence of serious adverse events (SAE)</measure>
      <time_frame>Approximately 12 months</time_frame>
      <description>Adverse Event (AE) is considered &quot;serious&quot; if the investigator or sponsor view any of the following outcomes: Death, life-threatening, persistent or significant disability/incapacity, congenital anomaly or birth defect,hospitalization, or medically important event.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Number of participants with laboratory value abnormalities and/or adverse events (AEs)</measure>
      <time_frame>Approximately 12 months</time_frame>
      <description>Number of participants with potentially clinically significant laboratory values.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Progression Free Survival(PFS)</measure>
      <time_frame>Approximately 12 months</time_frame>
      <description>PFS is defined as the duration from the subject's first dose of the investigational product to the first imaging confirmation of progressive disease per RECIST 1.1 by investigator evaluation or death due to any cause (whichever occurs first).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Duration Of Response (DOR)</measure>
      <time_frame>Approximately 12 months</time_frame>
      <description>DOR is defined as the time from the date of the first response (CR/PR) until the date of progressive disease as assessed by investigator evaluation per RECIST 1.1 or death due to any cause (whichever occurs first).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Overall Survival (OS)</measure>
      <time_frame>Approximately 12 months</time_frame>
      <description>OS is defined as the duration from the first dose of the investigational product to the time point when death occurs due to any cause.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Pharmacokinetics(PK) of QLS31905: Maximum concentration (Cmax)</measure>
      <time_frame>Approximately 12 months</time_frame>
      <description>Cmax will be derived from the PK serum samples collected.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>PK of QLS31905: Time of the maximum concentration (Tmax)</measure>
      <time_frame>Approximately 12 months</time_frame>
      <description>Tmax will be derived from the PK serum samples collected.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>PK of QLS31905: Terminal elimination half-life (T1/2)</measure>
      <time_frame>Approximately 12 months</time_frame>
      <description>T1/2 will be derived from the PK serum samples collected.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>PK of QLS31905: Clearance (CL)</measure>
      <time_frame>Approximately 12 months</time_frame>
      <description>CL will be derived from the PK serum samples collected.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>PK of QLS31905: Apparent volume of distribution during the terminal phase (Vz)</measure>
      <time_frame>Approximately 12 months</time_frame>
      <description>Vz will be derived from the PK serum samples collected.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Number of anti-drug antibody (ADA) Positive Participants</measure>
      <time_frame>Approximately 12 months</time_frame>
      <description>Immunogenicity will be measured by the number of participants that are ADA positive.</description>
    </secondary_outcome>
    <number_of_arms>3</number_of_arms>
    <enrollment type="Anticipated">115</enrollment>
    <condition>Solid Tumor</condition>
    <arm_group>
      <arm_group_label>QLS31905 + nab-paclitaxel + gemcitabine (Part A/B)</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Pancreatic cancer participants will be treated with QLS31905 in combination with nab-paclitaxel and gemcitabine for part A of the study to establish the recommended dose of QLS31905 for part B. In part B, the participants will be treated with QLS31905 at a dose determined by the part A of the study in combination with nab-paclitaxel and gemcitabine.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>QLS31905 + oxaliplatin + capecitabine (Part B)</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>In part B, gastric/gastroesophageal junction cancer participants will be treated with QLS31905 at dose determined by part A of the study in combination with oxaliplatin and capecitabine.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>QLS31905 + gemcitabine+cisplatin(Part B)</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>In part B, other solid tumor participants including but not limited to biliary tract cancer will be treated with QLS31905 at dose determined by part A in combination with standard chemotherapy recommended by guidelines.QLS31905 plus gemcitabine+ cisplatin as the first-line treatment of advanced biliary tract cancer.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>QLS31905</intervention_name>
      <description>Administered as an intravenous infusion.</description>
      <arm_group_label>QLS31905 + gemcitabine+cisplatin(Part B)</arm_group_label>
      <arm_group_label>QLS31905 + nab-paclitaxel + gemcitabine (Part A/B)</arm_group_label>
      <arm_group_label>QLS31905 + oxaliplatin + capecitabine (Part B)</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Nab paclitaxel</intervention_name>
      <description>125 mg/m2 administered as IV infusion on D1/D8/D15 of each cycle.</description>
      <arm_group_label>QLS31905 + nab-paclitaxel + gemcitabine (Part A/B)</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Gemcitabine</intervention_name>
      <description>1000 mg/m2 administered as IV infusion on D1/D8/D15 of each cycle.</description>
      <arm_group_label>QLS31905 + gemcitabine+cisplatin(Part B)</arm_group_label>
      <arm_group_label>QLS31905 + nab-paclitaxel + gemcitabine (Part A/B)</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Oxaliplatin</intervention_name>
      <description>85 mg/m2, intravenous infusion, D1/D15, up to 6 cycles.</description>
      <arm_group_label>QLS31905 + oxaliplatin + capecitabine (Part B)</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Capecitabine</intervention_name>
      <description>1000 mg/m2, oral, bid, D1-D7,D15-D21, up to 6 cycles.</description>
      <arm_group_label>QLS31905 + oxaliplatin + capecitabine (Part B)</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Cisplatin</intervention_name>
      <description>25 mg/m2, intravenous infusion, D1/D15, up to 6 cycles.</description>
      <arm_group_label>QLS31905 + gemcitabine+cisplatin(Part B)</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Subjects voluntarily participate in the study and sign the informed consent form;&#xD;
  &#xD;
            -  Eastern Cooperative Oncology Group (ECOG) performance status score of 0-1;&#xD;
  &#xD;
            -  Expected survival time ≥ 3 months;&#xD;
  &#xD;
            -  Histologically or cytologically confirmed locally advanced unresectable or metastatic&#xD;
               solid tumors;&#xD;
  &#xD;
            -  No prior systemic anti-tumor treatment for locally advanced unresectable or metastatic&#xD;
               disease;&#xD;
  &#xD;
            -  Tumor tissue samples determined to have moderate-to-high Claudin18.2 expression by&#xD;
               immunohistochemistry (IHC);&#xD;
  &#xD;
            -  At least one measurable lesion per RECIST v1.1;&#xD;
  &#xD;
            -  Patients with adequate cardiac, liver, renal function, etc.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  History of malignancies other than the target cancer within 5 years prior to the first&#xD;
               dose of the investigational product ;&#xD;
  &#xD;
            -  Underwent major organ surgery (excluding needle biopsy) or had significant trauma&#xD;
               within 28 days prior to enrollment, or requires elective surgery during the study;&#xD;
  &#xD;
            -  Known central nervous system metastases;&#xD;
  &#xD;
            -  Patients with hepatitis B; patients with hepatitis C; patients who test positive for&#xD;
               syphilis, or patients with a known history of HIV or positive HIV screening test;&#xD;
  &#xD;
            -  Patients with a known history of psychoactive drug abuse, alcohol abuse, or substance&#xD;
               abuse;&#xD;
  &#xD;
            -  Patients with added risks associated with the study or may interfere with the&#xD;
               interpretation of study results as determined by the investigator, or deemed&#xD;
               unsuitable by the investigator and/or sponsor.&#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>Lin Shen, M.D</last_name>
      <phone>010-881965671</phone>
      <email>linshenpku@163.com</email>
    </overall_contact>
    <location>
      <facility>
        <name>Beijing Cancer Hospital</name>
        <address>
          <city>Beijing</city>
          <state>Beijing</state>
          <zip>100142</zip>
          <country>China</country>
        </address>
      </facility>
    </location>
    <location_countries>
      <country>China</country>
    </location_countries>
    <verification_date>September 2023</verification_date>
    <study_first_submitted>August 30, 2023</study_first_submitted>
    <study_first_submitted_qc>September 10, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">September 18, 2023</study_first_posted>
    <last_update_submitted>September 10, 2023</last_update_submitted>
    <last_update_submitted_qc>September 10, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 18, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>CLDN18.2</keyword>
    <keyword>QLS31905</keyword>
    <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>Paclitaxel</mesh_term>
      <mesh_term>Gemcitabine</mesh_term>
      <mesh_term>Capecitabine</mesh_term>
      <mesh_term>Oxaliplatin</mesh_term>
    </intervention_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/NCT06041035
  org study id: QLS31905-201
  nct id: NCT06041035
  lead sponsor: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  This study aims to evaluate the efficacy and safety of QLS31905 plus chemotherapy in patients
        with Claudin18.2-positive advanced solid tumors.
  allocation: Non-Randomized
  intervention model: Parallel Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Maximum Tolerated Dose (MTD) (Part A)
  time frame: Approximately 12 months
  description: As measured by number of participants experiencing dose related toxicity (DLT) in each escalating cohort.
  measure: Phase 2 Recommended Dose（RP2D)(Part A)
  time frame: Approximately 12 months
  description: Monitor for MTD, and minimal efficacious dose by monitoring responses at different dose levels.
  measure: Objective response rate (ORR)(Part B)
  time frame: Approximately 12 months
  description: ORR is defined as the proportion of participants who have a best overall response of Complete Response (CR) or Partial Response (PR) as assessed by investigator evaluation per RECIST 1.1.
  measure: Safety assessed by Adverse Events (AEs)
  time frame: Approximately 12 months
  description: An AE is any untoward medical occurrence in a subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom,or disease (new or exacerbated) temporally associated with the use of a medicinal product.
  measure: Safety assessed by incidence of serious adverse events (SAE)
  time frame: Approximately 12 months
  description: Adverse Event (AE) is considered "serious" if the investigator or sponsor view any of the following outcomes: Death, life-threatening, persistent or significant disability/incapacity, congenital anomaly or birth defect,hospitalization, or medically important event.
  measure: Number of participants with laboratory value abnormalities and/or adverse events (AEs)
  time frame: Approximately 12 months
  description: Number of participants with potentially clinically significant laboratory values.
  measure: Progression Free Survival(PFS)
  time frame: Approximately 12 months
  description: PFS is defined as the duration from the subject's first dose of the investigational product to the first imaging confirmation of progressive disease per RECIST 1.1 by investigator evaluation or death due to any cause (whichever occurs first).
  measure: Duration Of Response (DOR)
  time frame: Approximately 12 months
  description: DOR is defined as the time from the date of the first response (CR/PR) until the date of progressive disease as assessed by investigator evaluation per RECIST 1.1 or death due to any cause (whichever occurs first).
  measure: Overall Survival (OS)
  time frame: Approximately 12 months
  description: OS is defined as the duration from the first dose of the investigational product to the time point when death occurs due to any cause.
  measure: Pharmacokinetics(PK) of QLS31905: Maximum concentration (Cmax)
  time frame: Approximately 12 months
  description: Cmax will be derived from the PK serum samples collected.
  measure: PK of QLS31905: Time of the maximum concentration (Tmax)
  time frame: Approximately 12 months
  description: Tmax will be derived from the PK serum samples collected.
  measure: PK of QLS31905: Terminal elimination half-life (T1/2)
  time frame: Approximately 12 months
  description: T1/2 will be derived from the PK serum samples collected.
  measure: PK of QLS31905: Clearance (CL)
  time frame: Approximately 12 months
  description: CL will be derived from the PK serum samples collected.
  measure: PK of QLS31905: Apparent volume of distribution during the terminal phase (Vz)
  time frame: Approximately 12 months
  description: Vz will be derived from the PK serum samples collected.
  measure: Number of anti-drug antibody (ADA) Positive Participants
  time frame: Approximately 12 months
  description: Immunogenicity will be measured by the number of participants that are ADA positive.
  arm group label: QLS31905 + nab-paclitaxel + gemcitabine (Part A/B)
  arm group type: Experimental
  description: Pancreatic cancer participants will be treated with QLS31905 in combination with nab-paclitaxel and gemcitabine for part A of the study to establish the recommended dose of QLS31905 for part B. In part B, the participants will be treated with QLS31905 at a dose determined by the part A of the study in combination with nab-paclitaxel and gemcitabine.
  arm group label: QLS31905 + oxaliplatin + capecitabine (Part B)
  arm group type: Experimental
  description: In part B, gastric/gastroesophageal junction cancer participants will be treated with QLS31905 at dose determined by part A of the study in combination with oxaliplatin and capecitabine.
  arm group label: QLS31905 + gemcitabine+cisplatin(Part B)
  arm group type: Experimental
  description: In part B, other solid tumor participants including but not limited to biliary tract cancer will be treated with QLS31905 at dose determined by part A in combination with standard chemotherapy recommended by guidelines.QLS31905 plus gemcitabine+ cisplatin as the first-line treatment of advanced biliary tract cancer.
  intervention type: Drug
  intervention name: QLS31905
  description: Administered as an intravenous infusion.
  arm group label: QLS31905 + gemcitabine+cisplatin(Part B)
  arm group label: QLS31905 + nab-paclitaxel + gemcitabine (Part A/B)
  arm group label: QLS31905 + oxaliplatin + capecitabine (Part B)
  intervention type: Drug
  intervention name: Nab paclitaxel
  description: 125 mg/m2 administered as IV infusion on D1/D8/D15 of each cycle.
  arm group label: QLS31905 + nab-paclitaxel + gemcitabine (Part A/B)
  intervention type: Drug
  intervention name: Gemcitabine
  description: 1000 mg/m2 administered as IV infusion on D1/D8/D15 of each cycle.
  arm group label: QLS31905 + gemcitabine+cisplatin(Part B)
  arm group label: QLS31905 + nab-paclitaxel + gemcitabine (Part A/B)
  intervention type: Drug
  intervention name: Oxaliplatin
  description: 85 mg/m2, intravenous infusion, D1/D15, up to 6 cycles.
  arm group label: QLS31905 + oxaliplatin + capecitabine (Part B)
  intervention type: Drug
  intervention name: Capecitabine
  description: 1000 mg/m2, oral, bid, D1-D7,D15-D21, up to 6 cycles.
  arm group label: QLS31905 + oxaliplatin + capecitabine (Part B)
  intervention type: Drug
  intervention name: Cisplatin
  description: 25 mg/m2, intravenous infusion, D1/D15, up to 6 cycles.
  arm group label: QLS31905 + gemcitabine+cisplatin(Part B)
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Lin Shen, M.D
  phone: 010-881965671
  email: linshenpku@163.com
  facility: 
  country: China
  responsible party type: Sponsor
  mesh term: Neoplasms
  mesh term: Paclitaxel
  mesh term: Gemcitabine
  mesh term: Capecitabine
  mesh term: Oxaliplatin