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/NCT05985707</url>
    </required_header>
    <id_info>
      <org_study_id>HERCKER-01</org_study_id>
      <nct_id>NCT05985707</nct_id>
    </id_info>
    <brief_title>KN026 Plus Chemotherapy ± KN-046 in HER2 Positive Colorectal Cancer and Biliary Carcinoma</brief_title>
    <official_title>The Efficacy and Safety of KN026 Combination Chemotherapy ± KN046 in HER2-Positive Advanced Colorectal Cancer and Biliary Tract Cancer as First-Line Treatment： a Phase Ⅱ Study</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Peking University Cancer Hospital &amp; Institute</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Peking University Cancer Hospital &amp; Institute</source>
    <oversight_info>
      <has_dmc>Yes</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 goal of this Interventional clinical trial is to learn about the efficacy and safety of&#xD;
        KN026 and chemotherapy ± KN046 in HER2-positive metastatic colorectal cancer and biliary&#xD;
        tract cancer. Participants will receive standard first-line chemotherapy (capecitabine +&#xD;
        oxaliplatin) combined with KN026 (a HER2-targeted bispecific antibody) ± KN046 （a&#xD;
        PD-L1/CTLA-4 targeted bispecific antibody）.&#xD;
      </textblock>
    </brief_summary>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">August 15, 2023</start_date>
    <completion_date type="Anticipated">December 31, 2026</completion_date>
    <primary_completion_date type="Anticipated">December 31, 2026</primary_completion_date>
    <phase>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>Overall response rate</measure>
      <time_frame>Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever occurs first), up to 24 months post-dose</time_frame>
      <description>Objective response rate (defined as CR+PR) is reported based on investigator's evaluation.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Progression free survival</measure>
      <time_frame>Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever occurs first), up to 24 months post-dose</time_frame>
      <description>Progression-free survival (PFS) is defined as the time from the date of the first dose to the earlier of the dates of the first objective documentation of radiographic progressive disease (PD) or death due to any cause.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Duration of response</measure>
      <time_frame>Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever occurs first), up to 24 months post-dose</time_frame>
      <description>Duration of response (DOR) is defined as the time from the date of the first response to the first objective documentation of radiographic progressive disease (PD) or death due to any cause.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Disease control rate</measure>
      <time_frame>Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever occurs first), up to 24 months post-dose</time_frame>
      <description>Disease control rate (defined as CR+PR+SD) is reported based on investigator's evaluation.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Time to response</measure>
      <time_frame>Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever occurs first), up to 24 months post-dose</time_frame>
      <description>Time to response (TOR) is defined as the time from the date of the first dose to the first objective documentation of radiographic objective response.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Overall survival</measure>
      <time_frame>Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever occurs first), up to 24 months post-dose</time_frame>
      <description>Overall survival (OS) is defined as the time from the date of first dose to the date of death from any cause.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Frequency of adverse events</measure>
      <time_frame>From the date of signing the informed consent form up to 30 (+7) days after last dose.</time_frame>
      <description>A treatment-emergent adverse event (TEAE) is defined as any adverse event not present prior to the initiation of drug treatment or any adverse event already present that worsens in intensity or frequency following exposure to the drug treatment. TEAEs were graded using National Cancer Institute (NCI)-CTCAE version 4.03.</description>
    </secondary_outcome>
    <number_of_arms>3</number_of_arms>
    <enrollment type="Anticipated">80</enrollment>
    <condition>HER2-positive Colorectal Cancer</condition>
    <condition>HER2-positive Biliary Tract Cancer</condition>
    <arm_group>
      <arm_group_label>A</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Arm A will include HER2-positive treatment-naive metastatic colorectal cancer patients, and the patients in this cohort will receive XELOX and KN026 treatment.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>B</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Arm B will include HER2-positive treatment-naive metastatic colorectal cancer patients, and the patients in this cohort will receive XELOX and KN026 + KN046 treatment.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>C</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Arm C will include HER2-positive treatment-naive metastatic biliary tract cancer patients, and the patients in this cohort will receive XELOX and KN026 + KN046 treatment.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>KN026</intervention_name>
      <description>KN026 is a novel bispecific antibody that simultaneously binds to two distinct HER2 epitopes.</description>
      <arm_group_label>A</arm_group_label>
      <arm_group_label>B</arm_group_label>
      <arm_group_label>C</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>KN046</intervention_name>
      <description>KN046 is a novel bispecific antibody that blocks both PD-L1 interaction with PD-1 and CTLA-4 interaction with CD80/CD86.</description>
      <arm_group_label>B</arm_group_label>
      <arm_group_label>C</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>XELOX</intervention_name>
      <description>XELOX is the standard first-line chemotherapy in metastatic colorectal cancer and biliary duct cancer.</description>
      <arm_group_label>A</arm_group_label>
      <arm_group_label>B</arm_group_label>
      <arm_group_label>C</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. Participants are able to comprehend the informed consent information and sign the&#xD;
               informed consent form.&#xD;
  &#xD;
            2. Participants ≥ 18 years old, of any gender.&#xD;
  &#xD;
            3. Cohorts A and B: Histologically confirmed unresectable HER2-positive metastatic&#xD;
               colorectal cancer, meeting the following criteria: a) Previously untreated with&#xD;
               systemic anti-tumor therapy, or the time from (neo)adjuvant chemotherapy completion to&#xD;
               disease recurrence &gt; 6 months; b) Gene sequencing shows wild-type RAS and BRAF&#xD;
               (participants' previous KRAS and BRAF test results are acceptable).&#xD;
  &#xD;
            4. Cohort C: Histologically confirmed unresectable HER2-positive biliary tract cancer,&#xD;
               including intrahepatic or extrahepatic bile duct cancer or gallbladder cancer: a)&#xD;
               Previously untreated with systemic anti-tumor therapy; b) If previously received&#xD;
               (neo)adjuvant radiotherapy, the time from treatment completion to disease recurrence&#xD;
               is &gt; 6 months.&#xD;
  &#xD;
            5. HER-2 positive defined as a) HER2 IHC 3+; b) HER2 IHC 2+ with HER2 amplification&#xD;
               (HER2/CEP17 &gt; 2.0 by ISH method)； c) HER copy number &gt; 6 by next-generation sequencing&#xD;
               using tumor tissue or circulating tumor DNA.&#xD;
  &#xD;
            6. LVEF ≥ 50%&#xD;
  &#xD;
          (9) Within 7 days before the first administration, hepatic function should meet the&#xD;
          following criteria:&#xD;
  &#xD;
            -  Total bilirubin ≤ 1.0 x ULN (≤ 1.5 x ULN for subjects with Gilbert's syndrome or liver&#xD;
               metastases)&#xD;
  &#xD;
            -  Transaminases (ALT/AST) ≤ 1.5 x ULN (≤ 3 x ULN for subjects with liver metastases)&#xD;
               (10) Within 7 days before the first administration, renal function should be as&#xD;
               follows:&#xD;
  &#xD;
            -  Serum creatinine ≤ 1.5 x ULN&#xD;
  &#xD;
            -  Creatinine clearance ≥ 60 mL/min (calculated using the Cockcroft-Gault formula) (11)&#xD;
               Within 7 days before the first administration, bone marrow function should meet the&#xD;
               following criteria:&#xD;
  &#xD;
            -  Hemoglobin ≥ 90 g/L&#xD;
  &#xD;
            -  Absolute neutrophil count ≥ 1.5 x 10^9/L&#xD;
  &#xD;
            -  Platelet count ≥ 100 x 10^9/L (12) TSH within the normal range; if TSH is abnormal,&#xD;
               free T3 and free T4 should be within the normal range.&#xD;
  &#xD;
               (13) Expected survival of ≥ 3 months. (14) Participants need to receive capecitabine&#xD;
               and oxaliplatin regimen chemotherapy based on clinical assessment.&#xD;
  &#xD;
               (15) Female participants of childbearing potential or male participants with partners&#xD;
               of childbearing potential must agree to use effective contraception from 7 days before&#xD;
               the first dose until 24 weeks after the last dose. Female participants of childbearing&#xD;
               potential must have a negative serum pregnancy test within 7 days before the first&#xD;
               dose.&#xD;
  &#xD;
               (16) Participants are capable and willing to comply with the study protocol, treatment&#xD;
               plan, laboratory tests, and other study-related procedures.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. Subjects with untreated active brain metastases or leptomeningeal metastases; if&#xD;
               subjects have received treatment for brain metastases and the lesions are stable&#xD;
               (stable brain imaging for at least 4 weeks before the first dose with no evidence of&#xD;
               new or enlarging brain lesions and no new neurological symptoms or stable neurological&#xD;
               symptoms at baseline), they are allowed to be enrolled.&#xD;
  &#xD;
            2. Ampullary carcinoma.&#xD;
  &#xD;
            3. Previous history of receiving any systemic anticancer therapy for metastatic tumors or&#xD;
               participation in interventional clinical trials.&#xD;
  &#xD;
            4. Within 14 days before the first dose, the subject requires a continuous 7-day&#xD;
               treatment of systemic corticosteroids (≥10 mg/day prednisone or equivalent of other&#xD;
               corticosteroids) or immunosuppressive agents; exceptions are inhaled or locally&#xD;
               applied corticosteroids or physiological replacement doses of corticosteroids for&#xD;
               adrenal insufficiency. Short-term (≤7 days) corticosteroids are allowed for prevention&#xD;
               (e.g., contrast dye allergy) or treatment of non-autoimmune conditions (e.g., delayed&#xD;
               hypersensitivity reactions caused by exposure to allergens).&#xD;
  &#xD;
            5. Received live vaccines (including attenuated live vaccines) within 28 days before the&#xD;
               first dose.&#xD;
  &#xD;
            6. Subjects with interstitial lung disease or requiring oral or intravenous&#xD;
               administration of corticosteroids.&#xD;
  &#xD;
            7. History or current presence of autoimmune diseases, including but not limited to&#xD;
               Crohn's disease, ulcerative colitis, systemic lupus erythematosus, sarcoidosis,&#xD;
               Wegener's granulomatosis (granulomatosis with polyangiitis), Graves' disease,&#xD;
               rheumatoid arthritis, hypophysitis, uveitis, autoimmune hepatitis, systemic sclerosis&#xD;
               (scleroderma), Hashimoto's thyroiditis (except under certain circumstances as outlined&#xD;
               below), autoimmune vasculitis, and autoimmune neurological disorders (such as&#xD;
               Guillain-Barre syndrome). The following conditions are exempted: type 1 diabetes,&#xD;
               stable hypothyroidism on hormone replacement therapy (including hypothyroidism caused&#xD;
               by autoimmune thyroid disease), and psoriasis or vitiligo not requiring systemic&#xD;
               treatment.&#xD;
  &#xD;
            8. History of another malignant tumor within 5 years before the first dose, except for&#xD;
               cured skin squamous cell carcinoma, basal cell carcinoma, non-muscle-invasive bladder&#xD;
               cancer, localized low-risk prostate cancer (defined as stage ≤T2a, Gleason score ≤6,&#xD;
               and prostate-specific antigen (PSA) ≤10 ng/mL at diagnosis, and patients who received&#xD;
               curative treatment without PSA biochemical recurrence), and in situ cervical/breast&#xD;
               cancer.&#xD;
  &#xD;
            9. Has uncontrolled comorbidities, including but not limited to the following conditions:&#xD;
  &#xD;
                 -  Active HBV or HCV infection.&#xD;
  &#xD;
                 -  Subjects with positive HBsAg and/or HCV antibodies during screening must undergo&#xD;
                    HBV DNA and/or HCV RNA testing. Subjects with HBV DNA ≤ 500 IU/mL (or ≤ 2000&#xD;
                    copies/mL) and/or HCV RNA negative can be enrolled; during the trial, the&#xD;
                    investigator will decide on monitoring HBV DNA based on the subject's situation.&#xD;
  &#xD;
                 -  Known HIV infection or history of AIDS.&#xD;
  &#xD;
                 -  Active tuberculosis.&#xD;
  &#xD;
                 -  Active infection or systemic use of antimicrobial drugs for more than 1 week&#xD;
                    within 28 days before the first dose of this study; unexplained fever within 2&#xD;
                    weeks before dosing.&#xD;
  &#xD;
                 -  Uncontrolled hypertension (resting blood pressure ≥ 160/100 mmHg), symptomatic&#xD;
                    heart failure (NYHA class II-IV), unstable angina or myocardial infarction within&#xD;
                    the past 6 months, or risk of QTc prolongation or arrhythmia (baseline QTc &gt; 470&#xD;
                    msec corrected by Fridericia method, difficult-to-correct hypokalemia, long QT&#xD;
                    syndrome, resting heart rate &gt; 100 bpm with atrial fibrillation, or severe&#xD;
                    valvular heart disease).&#xD;
  &#xD;
                 -  Active bleeding that cannot be controlled even with medical intervention.&#xD;
  &#xD;
           10. History of allogeneic bone marrow or organ transplantation.&#xD;
  &#xD;
           11. History of allergic reactions, hypersensitivity, or intolerance to antibody-based&#xD;
               drugs; history of significant drug allergies (e.g., severe allergic reactions,&#xD;
               immune-mediated hepatotoxicity, immune-mediated thrombocytopenia, or anemia).&#xD;
  &#xD;
           12. Pregnant and/or lactating females.&#xD;
  &#xD;
           13. Other conditions that, in the opinion of the investigator, may affect the safety or&#xD;
               compliance of the study drug treatment, including but not limited to moderate to large&#xD;
               pleural/peritoneal/pericardial effusion, difficult-to-correct&#xD;
               pleural/peritoneal/pericardial effusion, intestinal obstruction or subacute intestinal&#xD;
               obstruction, psychiatric disorders, etc.&#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>Jian Li</last_name>
      <phone>13601310849</phone>
      <email>oncogene@163.com</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Xicheng Wang</last_name>
      <phone>13439563949</phone>
      <email>xicheng_wang@hotmail.com</email>
    </overall_contact_backup>
    <location>
      <facility>
        <name>Peking University cancer hospital &amp; institution</name>
        <address>
          <city>Beijing</city>
          <state>State*</state>
          <zip>100142</zip>
          <country>China</country>
        </address>
      </facility>
      <contact>
        <last_name>Ting Xu, MD</last_name>
        <phone>18201137836</phone>
        <email>xtlmhxt@163.com</email>
      </contact>
      <contact_backup>
        <last_name>Zhenghang Wang, MD</last_name>
        <email>zhenghang_wang@bjmu.edu.cn</email>
      </contact_backup>
      <investigator>
        <last_name>Lin Shen</last_name>
        <role>Principal Investigator</role>
      </investigator>
      <investigator>
        <last_name>Jian Li</last_name>
        <role>Sub-Investigator</role>
      </investigator>
    </location>
    <location_countries>
      <country>China</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 2, 2023</study_first_submitted>
    <study_first_submitted_qc>August 2, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 14, 2023</study_first_posted>
    <last_update_submitted>August 17, 2023</last_update_submitted>
    <last_update_submitted_qc>August 17, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 21, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Peking University Cancer Hospital &amp; Institute</investigator_affiliation>
      <investigator_full_name>Shen Lin</investigator_full_name>
      <investigator_title>Professor</investigator_title>
    </responsible_party>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Colorectal Neoplasms</mesh_term>
      <mesh_term>Biliary Tract Neoplasms</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </patient_data>
    <!-- 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/NCT05985707
  org study id: HERCKER-01
  nct id: NCT05985707
  lead sponsor: 
  has dmc: Yes
  is fda regulated drug: No
  is fda regulated device: No
  The goal of this Interventional clinical trial is to learn about the efficacy and safety of
        KN026 and chemotherapy ± KN046 in HER2-positive metastatic colorectal cancer and biliary
        tract cancer. Participants will receive standard first-line chemotherapy (capecitabine +
        oxaliplatin) combined with KN026 (a HER2-targeted bispecific antibody) ± KN046 （a
        PD-L1/CTLA-4 targeted bispecific antibody）.
  allocation: Non-Randomized
  intervention model: Parallel Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Overall response rate
  time frame: Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever occurs first), up to 24 months post-dose
  description: Objective response rate (defined as CR+PR) is reported based on investigator's evaluation.
  measure: Progression free survival
  time frame: Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever occurs first), up to 24 months post-dose
  description: Progression-free survival (PFS) is defined as the time from the date of the first dose to the earlier of the dates of the first objective documentation of radiographic progressive disease (PD) or death due to any cause.
  measure: Duration of response
  time frame: Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever occurs first), up to 24 months post-dose
  description: Duration of response (DOR) is defined as the time from the date of the first response to the first objective documentation of radiographic progressive disease (PD) or death due to any cause.
  measure: Disease control rate
  time frame: Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever occurs first), up to 24 months post-dose
  description: Disease control rate (defined as CR+PR+SD) is reported based on investigator's evaluation.
  measure: Time to response
  time frame: Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever occurs first), up to 24 months post-dose
  description: Time to response (TOR) is defined as the time from the date of the first dose to the first objective documentation of radiographic objective response.
  measure: Overall survival
  time frame: Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever occurs first), up to 24 months post-dose
  description: Overall survival (OS) is defined as the time from the date of first dose to the date of death from any cause.
  measure: Frequency of adverse events
  time frame: From the date of signing the informed consent form up to 30 (+7) days after last dose.
  description: A treatment-emergent adverse event (TEAE) is defined as any adverse event not present prior to the initiation of drug treatment or any adverse event already present that worsens in intensity or frequency following exposure to the drug treatment. TEAEs were graded using National Cancer Institute (NCI)-CTCAE version 4.03.
  arm group label: A
  arm group type: Experimental
  description: Arm A will include HER2-positive treatment-naive metastatic colorectal cancer patients, and the patients in this cohort will receive XELOX and KN026 treatment.
  arm group label: B
  arm group type: Experimental
  description: Arm B will include HER2-positive treatment-naive metastatic colorectal cancer patients, and the patients in this cohort will receive XELOX and KN026 + KN046 treatment.
  arm group label: C
  arm group type: Experimental
  description: Arm C will include HER2-positive treatment-naive metastatic biliary tract cancer patients, and the patients in this cohort will receive XELOX and KN026 + KN046 treatment.
  intervention type: Drug
  intervention name: KN026
  description: KN026 is a novel bispecific antibody that simultaneously binds to two distinct HER2 epitopes.
  arm group label: A
  arm group label: B
  arm group label: C
  intervention type: Drug
  intervention name: KN046
  description: KN046 is a novel bispecific antibody that blocks both PD-L1 interaction with PD-1 and CTLA-4 interaction with CD80/CD86.
  arm group label: B
  arm group label: C
  intervention type: Drug
  intervention name: XELOX
  description: XELOX is the standard first-line chemotherapy in metastatic colorectal cancer and biliary duct cancer.
  arm group label: A
  arm group label: B
  arm group label: C
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Jian Li
  phone: 13601310849
  email: oncogene@163.com
  last name: Xicheng Wang
  phone: 13439563949
  email: xicheng_wang@hotmail.com
  facility: 
  contact: 
  contact backup: 
  investigator: 
  investigator: 
  country: China
  responsible party type: Principal Investigator
  investigator affiliation: Peking University Cancer Hospital & Institute
  investigator full name: Shen Lin
  investigator title: Professor
  mesh term: Colorectal Neoplasms
  mesh term: Biliary Tract Neoplasms
  sharing ipd: No