<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/NCT03838848</url>
  </required_header>
  <id_info>
    <org_study_id>KN046-201</org_study_id>
    <nct_id>NCT03838848</nct_id>
  </id_info>
  <brief_title>KN046 in Patients With Advanced Non-small Cell Lung Cancer</brief_title>
  <official_title>A Phase II Study to Evaluate the Efficacy, Safety, and Tolerability of KN046 in Patients With Advanced Non-small Cell Lung Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Jiangsu Alphamab Biopharmaceuticals Co., Ltd</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Jiangsu Alphamab Biopharmaceuticals 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 II, open label, multicenter study in subjects with advanced non-small cell&#xD;
      lung cancer.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      A Phase 2 Clinical Study to Evaluate the Efficacy, Safety, and Tolerability of KN046 in&#xD;
      Subjects with Advanced Non-small Cell Lung Cancer&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Cohort A,B,C end enrollments. Cohort D and E were considered to have no significant clinical&#xD;
    benefit at the SMC meeting and decided to terminate enrollment.&#xD;
  </why_stopped>
  <start_date type="Actual">May 5, 2019</start_date>
  <completion_date type="Actual">July 30, 2022</completion_date>
  <primary_completion_date type="Actual">July 30, 2022</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>Sequential Assignment</intervention_model>
    <intervention_model_description>Cohort A, B and C are carried out in sequence, a Scientific Monitoring Committee (SMC) will decide whether to enter the next group (A to B, B to C).&#xD;
Cohort D: 1L NSCLC (EGFR-sensitive mutation (Ex19del or L858R), progression after at least one line treatemtn of EGFR TKIs, and no prior systemic platinum-containing chemotherapy); Cohort E: ≥ 2L NSCLC (failure or intolerance of 1L platinum-doublet chemotherapy; and failure of PD-1/PD-L1 checkpoint inhibitor therapy);</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>ORR</measure>
    <time_frame>2 years</time_frame>
    <description>clinical response rate (ORR) as determined by the independent review board (IRC) based on RECIST 1.1 criteria</description>
  </primary_outcome>
  <primary_outcome>
    <measure>DOR</measure>
    <time_frame>2 years</time_frame>
    <description>clinical response time (DOR) as determined by the independent review board (IRC) based on RECIST 1.1 criteria</description>
  </primary_outcome>
  <number_of_arms>5</number_of_arms>
  <enrollment type="Actual">120</enrollment>
  <condition>Stage IV Non-small Cell Lung Cancer</condition>
  <arm_group>
    <arm_group_label>Cohort A</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects with Non-small Cell Lung Cancer (NSCLC) (failed or did not tolerant to platinum-containing regime and did not treat with programmed cell death protein 1/the programmed death-ligand 1 (PD1/PDL-1) checkpoint inhibitor previously) will receive KN046 3 milligram per kilogram (mg/kg), every other weeks (Q2W)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort B</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects with NSCLC (failed or did not tolerant to platinum-containing regime and did not treat with PD1/PDL-1 checkpoint inhibitor previously) will receive KN046 5 mg/kg, Q2W</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort C</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects with NSCLC (failed or did not tolerant to platinum-containing regime and failed to PD1/PDL-1 checkpoint inhibitor) will receive KN046</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort D</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>1L NSCLC (EGFR-sensitive mutation (Ex19del or L858R), progression after at least one line treatemtn of EGFR TKIs, and no prior systemic platinum-containing chemotherapy), will receive KN046 5 mg/kg Q3W in combination with pemetrexed and carboplatin</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort E</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>≥ 2L NSCLC (failure or intolerance of 1L platinum-doublet chemotherapy; and failure of PD-1/PD-L1 checkpoint inhibitor therapy), will receive KN046 in combination with ningetinib</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>KN046</intervention_name>
    <description>3mg/kg, Q2W, intravenous injection (IV)</description>
    <arm_group_label>Cohort A</arm_group_label>
    <other_name>Recombinant Humanized PD-L1/CTLA-4 Bispecific Single Domain Antibody Fc Fusion Protein Injection</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>KN046</intervention_name>
    <description>5mg/kg, Q2W, intravenous injection (IV)</description>
    <arm_group_label>Cohort B</arm_group_label>
    <arm_group_label>Cohort C</arm_group_label>
    <arm_group_label>Cohort E</arm_group_label>
    <other_name>Recombinant Humanized PD-L1/CTLA-4 Bispecific Single Domain Antibody Fc Fusion Protein Injection</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>KN046</intervention_name>
    <description>5mg/kg, Q3W, intravenous injection (IV)</description>
    <arm_group_label>Cohort D</arm_group_label>
    <other_name>Recombinant Humanized PD-L1/CTLA-4 Bispecific Single Domain Antibody Fc Fusion Protein Injection</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Carboplatin</intervention_name>
    <description>AUC 5 IV Q3W; total dose calculated according to the Calvert formula, with the highest dose not exceeding 750 mg; 4 cycles.</description>
    <arm_group_label>Cohort D</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Pemetrexed</intervention_name>
    <description>500 mg/m2, Q3W, intravenous injection (IV)</description>
    <arm_group_label>Cohort D</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ningetinib</intervention_name>
    <description>Oral, QD</description>
    <arm_group_label>Cohort E</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Signed inform consent form(ICF);&#xD;
&#xD;
          2. Age ≥ 18 years and ≤ 75 years, male or female;&#xD;
&#xD;
          3. Histologically or cytologically documented NSCLC,Stage IV (AJCC Version 8) .&#xD;
&#xD;
          4. At least one measurable lesion according to Response Evaluation Criteria In Solid&#xD;
             Tumors（RECISIT） v 1.1;&#xD;
&#xD;
          5. Biopsy specimens obtained from nonradiated areas within 1 year, formalin-fixed,&#xD;
             paraffin-embedded blocks containing tumor tissues suitable for biomarker&#xD;
             determination, or 15-20 slides (more slides are encouraged to be provided with a&#xD;
             minimum of 8 slides; if less than 8 slides are provided, the subject may also be&#xD;
             enrolled after consultation and agreement between the Sponsor and the investigator);&#xD;
             and fresh biopsy samples collected within 42 days prior to the first dose are required&#xD;
             for determination in Cohorts C, D, and E;&#xD;
&#xD;
          6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1;&#xD;
&#xD;
          7. Life expectancy &gt; 12 weeks;&#xD;
&#xD;
          8. Female patients and males with partners of childbearing potential should be using&#xD;
             highly effective contraceptive measures (failure rate of less than 1% per year).&#xD;
             Contraception should be continued for a period of 24 weeks after dosing has been&#xD;
             completed.&#xD;
&#xD;
          9. Ability to comply with treatment, procedures and pharmacokinetics (PK) sample&#xD;
             collection and the required study follow-up procedures&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Known brain metastasis or another Central Nervous System (CNS) metastasis that is&#xD;
             either symptomatic or untreated.&#xD;
&#xD;
          2. Having participated in any interventional clinical study within 28 days prior to drug&#xD;
             administration in this study.&#xD;
&#xD;
          3. Having received other anti-tumor therapy within 28 days before administration in this&#xD;
             study, including traditional Chinese medicine with anti-tumor indications;&#xD;
&#xD;
          4. Having received major surgical treatment (such as major abdominal, transthoracic&#xD;
             surgery; excluding diagnostic aspiration or peripheral vascular access replacement)&#xD;
             within 28 days prior to drug administration in this study;&#xD;
&#xD;
          5. Having received radical radiotherapy within 3 months prior to drug administration in&#xD;
             this study; palliative radiation therapy within 2 weeks prior to the first dose is&#xD;
             allowed, the radiation dose meets the diagnostic and treatment criteria for local&#xD;
             palliative treatment, and the radiation coverage is less than 30% of the bone marrow&#xD;
             area;&#xD;
&#xD;
          6. Subjects who require systemic corticosteroids (≥ 10 mg/day prednisone or equivalent&#xD;
             dose of other corticosteroids) or immunosuppressive therapy within 14 days prior to&#xD;
             drug administration in this study; except for inhaled or topical corticosteroids, or&#xD;
             physiologic replacement doses of corticosteroids for adrenal insufficiency; short-term&#xD;
             (≤ 7 days) corticosteroids are allowed for prophylaxis (e.g., contrast media allergy)&#xD;
             or for the treatment of non-autoimmune disorders (e.g., delayed type hypersensitivity&#xD;
             due to contact allergens);&#xD;
&#xD;
          7. Having received live vaccines (including live attenuated vaccines) within 28 days&#xD;
             prior to drug administration in this study;&#xD;
&#xD;
          8. Previous or current interstitial pneumonia/pneumopathy; Subjects with active&#xD;
             autoimmune diseases or history of autoimmune diseases should be excluded.&#xD;
&#xD;
          9. Subjects who have prior or current autoimmune diseases;&#xD;
&#xD;
         10. Subjects who have other malignancies within 5 years before the first dose;&#xD;
&#xD;
         11. Active Hepatitis B Virus (HBV) or Hepatitis C Virus (HCV) infection, Known HIV&#xD;
             infection or known history of acquired immune deficient syndrome (AIDS).&#xD;
&#xD;
         12. Any unresolved the Common Terminology Criteria for Adverse Events (CTCAE) Grade ≥ 2&#xD;
             toxicities from prior anti-cancer therapy except for vitiligo, alopecia;&#xD;
&#xD;
         13. History of allogeneic bone marrow or organ transplantation;&#xD;
&#xD;
         14. Prior history of allergic reaction, hypersensitivity reaction, and intolerance to&#xD;
             antibody drugs; history of significant allergy to drugs;&#xD;
&#xD;
         15. Pregnant and/or lactating women;&#xD;
&#xD;
         16. Other conditions that, in the opinion of the investigator, will affect the safety or&#xD;
             compliance of the subjects with the study treatment, including but not limited to&#xD;
             psychiatric disorders, uncontrolled moderate to severe serous cavity effusions with&#xD;
             large amounts of serous cavity effusions or requiring repeated drainage.&#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>Caicun Zhou, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Shanghai Pulmonary Hospital, Shanghai, China</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Shanghai Pulmonary Hospital</name>
      <address>
        <city>Shanghai</city>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>February 2023</verification_date>
  <study_first_submitted>February 1, 2019</study_first_submitted>
  <study_first_submitted_qc>February 10, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 12, 2019</study_first_posted>
  <last_update_submitted>February 28, 2023</last_update_submitted>
  <last_update_submitted_qc>February 28, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">March 2, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lung Neoplasms</mesh_term>
    <mesh_term>Carcinoma, Non-Small-Cell Lung</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Carboplatin</mesh_term>
    <mesh_term>Pemetrexed</mesh_term>
    <mesh_term>Antibodies</mesh_term>
    <mesh_term>Immunoglobulins</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03838848
org study id: KN046-201
nct id: NCT03838848
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
This is a phase II, open label, multicenter study in subjects with advanced non-small cell
      lung cancer.
A Phase 2 Clinical Study to Evaluate the Efficacy, Safety, and Tolerability of KN046 in
      Subjects with Advanced Non-small Cell Lung Cancer
allocation: Non-Randomized
intervention model: Sequential Assignment
intervention model description: Cohort A, B and C are carried out in sequence, a Scientific Monitoring Committee (SMC) will decide whether to enter the next group (A to B, B to C).
Cohort D: 1L NSCLC (EGFR-sensitive mutation (Ex19del or L858R), progression after at least one line treatemtn of EGFR TKIs, and no prior systemic platinum-containing chemotherapy); Cohort E: ≥ 2L NSCLC (failure or intolerance of 1L platinum-doublet chemotherapy; and failure of PD-1/PD-L1 checkpoint inhibitor therapy);
primary purpose: Treatment
masking: None (Open Label)
measure: ORR
time frame: 2 years
description: clinical response rate (ORR) as determined by the independent review board (IRC) based on RECIST 1.1 criteria
measure: DOR
time frame: 2 years
description: clinical response time (DOR) as determined by the independent review board (IRC) based on RECIST 1.1 criteria
arm group label: Cohort A
arm group type: Experimental
description: Subjects with Non-small Cell Lung Cancer (NSCLC) (failed or did not tolerant to platinum-containing regime and did not treat with programmed cell death protein 1/the programmed death-ligand 1 (PD1/PDL-1) checkpoint inhibitor previously) will receive KN046 3 milligram per kilogram (mg/kg), every other weeks (Q2W)
arm group label: Cohort B
arm group type: Experimental
description: Subjects with NSCLC (failed or did not tolerant to platinum-containing regime and did not treat with PD1/PDL-1 checkpoint inhibitor previously) will receive KN046 5 mg/kg, Q2W
arm group label: Cohort C
arm group type: Experimental
description: Subjects with NSCLC (failed or did not tolerant to platinum-containing regime and failed to PD1/PDL-1 checkpoint inhibitor) will receive KN046
arm group label: Cohort D
arm group type: Experimental
description: 1L NSCLC (EGFR-sensitive mutation (Ex19del or L858R), progression after at least one line treatemtn of EGFR TKIs, and no prior systemic platinum-containing chemotherapy), will receive KN046 5 mg/kg Q3W in combination with pemetrexed and carboplatin
arm group label: Cohort E
arm group type: Experimental
description: ≥ 2L NSCLC (failure or intolerance of 1L platinum-doublet chemotherapy; and failure of PD-1/PD-L1 checkpoint inhibitor therapy), will receive KN046 in combination with ningetinib
intervention type: Drug
intervention name: KN046
description: 3mg/kg, Q2W, intravenous injection (IV)
arm group label: Cohort A
other name: Recombinant Humanized PD-L1/CTLA-4 Bispecific Single Domain Antibody Fc Fusion Protein Injection
intervention type: Drug
intervention name: KN046
description: 5mg/kg, Q2W, intravenous injection (IV)
arm group label: Cohort B
arm group label: Cohort C
arm group label: Cohort E
other name: Recombinant Humanized PD-L1/CTLA-4 Bispecific Single Domain Antibody Fc Fusion Protein Injection
intervention type: Drug
intervention name: KN046
description: 5mg/kg, Q3W, intravenous injection (IV)
arm group label: Cohort D
other name: Recombinant Humanized PD-L1/CTLA-4 Bispecific Single Domain Antibody Fc Fusion Protein Injection
intervention type: Drug
intervention name: Carboplatin
description: AUC 5 IV Q3W; total dose calculated according to the Calvert formula, with the highest dose not exceeding 750 mg; 4 cycles.
arm group label: Cohort D
intervention type: Drug
intervention name: Pemetrexed
description: 500 mg/m2, Q3W, intravenous injection (IV)
arm group label: Cohort D
intervention type: Drug
intervention name: Ningetinib
description: Oral, QD
arm group label: Cohort E
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Caicun Zhou, MD
role: Principal Investigator
affiliation: Shanghai Pulmonary Hospital, Shanghai, China
facility: 
country: China
responsible party type: Sponsor
mesh term: Lung Neoplasms
mesh term: Carcinoma, Non-Small-Cell Lung
mesh term: Carboplatin
mesh term: Pemetrexed
mesh term: Antibodies
mesh term: Immunoglobulins
sharing ipd: No