<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/NCT04478461</url>
  </required_header>
  <id_info>
    <org_study_id>MW11-2019-CP101</org_study_id>
    <nct_id>NCT04478461</nct_id>
  </id_info>
  <brief_title>Safety, Tolerability, and Pharmacokinetics of MW11 in Patients With Advanced Solid Tumors</brief_title>
  <official_title>A Phase Ia Clinical Trial to Assess Safety, Tolerability, and Pharmacokinetics of a Recombinant Humanized Anti-PD-1 Monoclonal Antibody (MW11) for Injection in Patients With Advanced Solid Tumors</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Mabwell (Shanghai) Bioscience Co., Ltd.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Mabwell (Shanghai) Bioscience 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 is a phase Ia, single-center, open label, dose escalation clinical study to evaluate the&#xD;
      safety, tolerability, pharmacokinetics, immunogenicity and anti-tumor efficacy of MW11 (a&#xD;
      recombinant humanized anti-PD-1 monoclonal antibody) for injection in patients with advanced&#xD;
      solid tumors.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The enrollment mainly depends on &quot;3+3&quot; principle. A total of 3 or 4 dose groups will be&#xD;
      evaluated during the dose escalation period: 1, 3, 10 mg/kg, and maybe an additional fixed&#xD;
      dose (e.g., to evaluate 200 mg or other fixed dose as RP2D). The drug is scheduled to be&#xD;
      administrated Q3W. Actual dose increments or dosing frequency may be adjusted according to PK&#xD;
      data and safety of MW11. Safety, tolerability, and DLT will be assessed within 3 weeks (21&#xD;
      days) after initial administration. Anti-tumor efficacy will be assessed every 6 weeks during&#xD;
      the first 24 weeks and every 12 weeks ever since. The study will be divided into screening&#xD;
      period and treatment period. The drug administration will be continued until the&#xD;
      investigators consider that the subjects will no longer benefit from the treatment, or the&#xD;
      subjects meet intolerable toxicity, or the subjects withdraw the informed consent, or disease&#xD;
      progression occurs.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">September 3, 2020</start_date>
  <completion_date type="Anticipated">February 2, 2023</completion_date>
  <primary_completion_date type="Anticipated">January 5, 2023</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>Adverse Event (AE )</measure>
    <time_frame>2 years</time_frame>
    <description>safety evaluation</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Severity Adverse Event (SAE)</measure>
    <time_frame>2 years</time_frame>
    <description>safety evaluation</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Elimination half life（t1/2）</measure>
    <time_frame>2 years</time_frame>
    <description>safety/efficacy evaluation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area under the concentration-time curve（AUC）</measure>
    <time_frame>2 years</time_frame>
    <description>safety/efficacy evaluation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>volume of distribution （Vz）</measure>
    <time_frame>2 years</time_frame>
    <description>safety/efficacy evaluation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Plasma Clearance （CL）</measure>
    <time_frame>2 years</time_frame>
    <description>safety/efficacy evaluation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximum Plasma Concentration（Cmax）</measure>
    <time_frame>2 years</time_frame>
    <description>safety/efficacy evaluation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to maximum plasma concentration（Tmax）</measure>
    <time_frame>2 years</time_frame>
    <description>safety/efficacy evaluation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Objective remission rate (ORR)</measure>
    <time_frame>2 years</time_frame>
    <description>efficacy evaluation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Disease control rate (DCR)</measure>
    <time_frame>2 years</time_frame>
    <description>efficacy evaluation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of remission (DOR)</measure>
    <time_frame>2 years</time_frame>
    <description>efficacy evaluation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression free survival (PFS)</measure>
    <time_frame>2 years</time_frame>
    <description>efficacy evaluation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival (OS)</measure>
    <time_frame>2 years</time_frame>
    <description>efficacy evaluation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants with positive anti drug antibody (ADA)</measure>
    <time_frame>2 years</time_frame>
    <description>safety evaluation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants with positive neutralizing antibody (Nab)</measure>
    <time_frame>2 years</time_frame>
    <description>safety evaluation</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">21</enrollment>
  <condition>Advanced Solid Tumor</condition>
  <arm_group>
    <arm_group_label>MW11 injection</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>1, 3, 10 mg/kg and maybe an additional fixed dose (e.g., to evaluate 200 mg or other fixed dose as RP2D). The drug is scheduled to be administrated Q3W.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>PD-1 monoclonal antibody</intervention_name>
    <description>The enrollment mainly depends on &quot;3+3&quot; principle. A total of 3 or 4 dose groups will be evaluated during the dose escalation period: 1, 3, 10 mg/kg, and maybe an additional fixed dose (e.g., to evaluate 200 mg or other fixed dose as RP2D). The drug is scheduled to be administrated Q3W</description>
    <arm_group_label>MW11 injection</arm_group_label>
    <other_name>MW11 injection</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Men and women aged from 18 to 75 (including 18 and 75).&#xD;
&#xD;
          2. Pathological diagnosis of advanced or metastatic solid tumors.&#xD;
&#xD;
          3. Advanced solid tumors that are progressed after standard antitumor therapy and can not&#xD;
             accept or refuse to receive standard treatment.&#xD;
&#xD;
          4. The ECOG score is 0 or 1.&#xD;
&#xD;
          5. The subjects are expected to survive at least 3 months.&#xD;
&#xD;
          6. Subjects must have at least 1 measurable lesion according to response evaluation&#xD;
             criteria in solid tumors RECIST V1.1. The measurable lesion must be absent from the&#xD;
             previous radiotherapy area or have progressed radiologically 4 weeks after&#xD;
             radiotherapy.&#xD;
&#xD;
          7. The subjects have proper organ and hematopoietic function, no serious heart, lung,&#xD;
             liver, renal function abnormalities or immune deficiency according to the following&#xD;
             laboratory tests:&#xD;
&#xD;
             Hematology: Absolute neutrophils count (ANC) ≥ 1.5×109/L, platelet ≥ 100×109/L,&#xD;
             hemoglobin ≥ 90g/L.&#xD;
&#xD;
             Renal function: serum creatinine ≤ 1.5 times the upper limit of normal value (ULN) or&#xD;
             creatinine clearance ≥ 50 mL/ min (Chockcroft-Gault formula was used for creatinine&#xD;
             clearance).&#xD;
&#xD;
             Liver function: AST and ALT ≤ 2.5 times ULN(AST and ALT ≤ 5 times ULN in patients with&#xD;
             liver cancer or liver metastasis; serum total bilirubin (TBIL) ≤ 1.5 times ULN;&#xD;
             alkaline phosphatase ≤ 1.5 times ULN(alkaline phosphatase≤ 5 times ULN in patients&#xD;
             with liver cancer or liver metastasis, or patients with bone metastasis).&#xD;
&#xD;
             Coagulation function: international normalized ratio (INR) ≤ 2 times ULN, or activated&#xD;
             partial thromboplastin time (APTT) ≤ 1.5 times ULN (except for the subjects who are&#xD;
             receiving anticoagulant therapy).&#xD;
&#xD;
          8. Male subjects with fertility and female subjects of reproductive age are willing to&#xD;
             take effective contraceptive measures from the signing of informed consent until 6&#xD;
             months after the last dose of drug administration. Female subjects of reproductive age&#xD;
             (before menopause and women after menopause within 2 years) must have negative blood&#xD;
             pregnancy test results within 7 days before the first drug administration.&#xD;
&#xD;
          9. Subjects sign informed consent voluntarily, to make sure they understand the study and&#xD;
             are willing to follow and able to complete all trial procedures.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Prior or current medical conditions:&#xD;
&#xD;
          1. Previous history of other malignant tumors (any malignant tumor other than the tumor&#xD;
             species treated in this study), except that the tumor has been cured for ≥ 2 years&#xD;
             before screening and treatment is not required during the study period.&#xD;
&#xD;
          2. Brain metastases.&#xD;
&#xD;
          3. Prior adverse reactions failed to recover to CTCAE V5.0 grade score ≤ 1, with the&#xD;
             exception of residual hair loss effect.&#xD;
&#xD;
          4. Fluid accumulations in the body cavity (pleural effusion, ascites, pericardial&#xD;
             effusion, etc.) that are not well controlled and require local treatment or repeated&#xD;
             drainage.&#xD;
&#xD;
          5. With active, or history of autoimmune diseases that may recur (E.G. systemic lupus&#xD;
             erythematosus, rheumatoid arthritis, inflammatory bowel disease, autoimmune thyroid&#xD;
             disease, multiple sclerosis, vasculitis, glomerulonephritis, etc.) , or high-risk&#xD;
             patients, such as those who have received an organ transplant and require&#xD;
             immunosuppressive therapy. But subjects with the following diseases are allowed to be&#xD;
             enrolled:&#xD;
&#xD;
             Subjects with type I diabetes whose condition is stable after receiving fixed dose of&#xD;
             insulin (HgbA1C ≤ 6.5%).&#xD;
&#xD;
             Autoimmune hypothyroidism requiring only hormone replacement therapy. Vitiligo, or&#xD;
             skin diseases that do not require systemic treatment (such as eczema that accounts for&#xD;
             less than 10% of the body surface, psoriasis without ophthalmic symptoms, etc.).&#xD;
&#xD;
          6. Sudden onset of pulmonary disease, Interstitial lung disease or pneumonia, or other&#xD;
             uncontrolled systemic disease including diabetes, pulmonary fibrosis, acute lung&#xD;
             disease, cardiovascular disease including hypertension (for example, LVEF ≤50% or NYHA&#xD;
             ≥ III) , with the exception of locally interstitial pneumonia due to radiotherapy.&#xD;
&#xD;
          7. Subjects infected by human immunodeficiency virus (HIV), or with other acquired or&#xD;
             congenital immunodeficiency diseases, or with a history of organ transplantation or&#xD;
             stem cell transplantation.&#xD;
&#xD;
          8. Subjects with active tuberculosis infection within 5 years before enrollment.&#xD;
&#xD;
          9. Subjects who were seriously infected within 4 weeks prior to the first drug&#xD;
             administration, or who had any signs or symptoms of active infection within 2 weeks&#xD;
             priorly, or who required antibiotic treatment within 2 weeks priorly (except for the&#xD;
             prophylactic antibiotics); or patients who had unexplained fever &gt;38.5℃ before the&#xD;
             first drug administration (subject with fever caused by tumor can be enrolled&#xD;
             according to the investigator's judgment).&#xD;
&#xD;
             Prior medication or treatment:&#xD;
&#xD;
         10. Patients who have received anti-PD-1 or PD-L1 antibody therapy or have received any&#xD;
             other antibody/drug (such as CTLA-4) therapy targeting T-cell co-regulatory proteins&#xD;
             (immune checkpoint) within 12 weeks prior to the first drug administration of the&#xD;
             study.&#xD;
&#xD;
         11. Subjects who have received anti-tumor therapy except:&#xD;
&#xD;
             The interval between systemic radiotherapy and the first drug administration of this&#xD;
             study is ≥ 4 weeks, and the interval of local or bone metastasis radiotherapy is ≥ 2&#xD;
             weeks. No radiological agents were taken within 8 weeks prior to the first drug&#xD;
             administration of this study.&#xD;
&#xD;
             Prior chemotherapy interval ≥ 4 weeks, immunotherapy, biological therapy (tumor&#xD;
             vaccine, cytokines, or growth factors that control cancer), or approved targeted and&#xD;
             other therapies, must be completed before the first drug administration in this study,&#xD;
             and the interval must be no less than 5 half-lives or at least 6 weeks (whichever is&#xD;
             longer).&#xD;
&#xD;
             TCM treatment should be completed at least 14 days before the first drug&#xD;
             administration in this study.&#xD;
&#xD;
         12. Subjects require systemic corticosteroids (the dosage is equivalent to &gt;10 mg&#xD;
             prednisone per day) or other immunosuppressive drugs within 14 days prior to&#xD;
             enrollment. Enrollment is allowed in the following cases:&#xD;
&#xD;
             Subjects are allowed to use topical or inhaled glucocorticoids. Subjects are allowed&#xD;
             to use glucocorticoids in short-term (≤ 7 days) for the prevention or treatment of&#xD;
             non-autoimmune allergic diseases that do not occur frequently.&#xD;
&#xD;
         13. Subjects who have received immunotherapy and had an immune-related adverse event&#xD;
             (irAE) level ≥ 3.&#xD;
&#xD;
             History of allergies, general conditions and others:&#xD;
&#xD;
         14. A subject is known to have had a prior severe allergic reaction to a macromolecular&#xD;
             protein preparation/monoclonal antibody or any component of the tested drug (CTCAE&#xD;
             V5.0 rating is greater than level 3).&#xD;
&#xD;
         15. Subjects with chronic hepatitis B/ active hepatitis C/ syphilis. However, hepatitis B&#xD;
             virus carriers, stable hepatitis B after drug treatment (DNA ≤ normal value), and&#xD;
             cured hepatitis C patients (HCV RNA negative) can be enrolled.&#xD;
&#xD;
         16. Subjects who participated in other drug clinical trials within 4 weeks prior to&#xD;
             enrollment.&#xD;
&#xD;
         17. Subjects who had major surgery within 4 weeks prior to screening or who are expected&#xD;
             to have major surgery during the study period (including the 28-day screening period).&#xD;
&#xD;
         18. Subjects with history of alcohol, drug or substance abuse in the last 1 year.&#xD;
&#xD;
         19. Subjects with clear history of neurological or psychiatric disorders, such as&#xD;
             epilepsy, dementia, or poor compliance.&#xD;
&#xD;
         20. Females who are pregnant or breastfeeding.&#xD;
&#xD;
         21. Subjects with any other medical condition that is considered to affect the subject's&#xD;
             safety.&#xD;
&#xD;
         22. The subjects that the investigator considers unsuitable for the study due to other&#xD;
             reasons.&#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>Suxia Luo, professor</last_name>
    <role>Principal Investigator</role>
    <affiliation>Henan Cancer Hospital</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Shan An</last_name>
    <phone>13613865536</phone>
    <email>watermelonas@163.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>Henan Cancer Hospital</name>
      <address>
        <city>Zhengzhou</city>
        <state>Henan</state>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Suxia Luo</last_name>
    </contact>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>November 2020</verification_date>
  <study_first_submitted>July 14, 2020</study_first_submitted>
  <study_first_submitted_qc>July 16, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 20, 2020</study_first_posted>
  <last_update_submitted>November 11, 2020</last_update_submitted>
  <last_update_submitted_qc>November 11, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">November 13, 2020</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>Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Antibodies</mesh_term>
    <mesh_term>Antibodies, Monoclonal</mesh_term>
  </intervention_browse>
  <!-- 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/NCT04478461
org study id: MW11-2019-CP101
nct id: NCT04478461
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This is a phase Ia, single-center, open label, dose escalation clinical study to evaluate the
      safety, tolerability, pharmacokinetics, immunogenicity and anti-tumor efficacy of MW11 (a
      recombinant humanized anti-PD-1 monoclonal antibody) for injection in patients with advanced
      solid tumors.
The enrollment mainly depends on "3+3" principle. A total of 3 or 4 dose groups will be
      evaluated during the dose escalation period: 1, 3, 10 mg/kg, and maybe an additional fixed
      dose (e.g., to evaluate 200 mg or other fixed dose as RP2D). The drug is scheduled to be
      administrated Q3W. Actual dose increments or dosing frequency may be adjusted according to PK
      data and safety of MW11. Safety, tolerability, and DLT will be assessed within 3 weeks (21
      days) after initial administration. Anti-tumor efficacy will be assessed every 6 weeks during
      the first 24 weeks and every 12 weeks ever since. The study will be divided into screening
      period and treatment period. The drug administration will be continued until the
      investigators consider that the subjects will no longer benefit from the treatment, or the
      subjects meet intolerable toxicity, or the subjects withdraw the informed consent, or disease
      progression occurs.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Adverse Event (AE )
time frame: 2 years
description: safety evaluation
measure: Severity Adverse Event (SAE)
time frame: 2 years
description: safety evaluation
measure: Elimination half life（t1/2）
time frame: 2 years
description: safety/efficacy evaluation
measure: Area under the concentration-time curve（AUC）
time frame: 2 years
description: safety/efficacy evaluation
measure: volume of distribution （Vz）
time frame: 2 years
description: safety/efficacy evaluation
measure: Plasma Clearance （CL）
time frame: 2 years
description: safety/efficacy evaluation
measure: Maximum Plasma Concentration（Cmax）
time frame: 2 years
description: safety/efficacy evaluation
measure: Time to maximum plasma concentration（Tmax）
time frame: 2 years
description: safety/efficacy evaluation
measure: Objective remission rate (ORR)
time frame: 2 years
description: efficacy evaluation
measure: Disease control rate (DCR)
time frame: 2 years
description: efficacy evaluation
measure: Duration of remission (DOR)
time frame: 2 years
description: efficacy evaluation
measure: Progression free survival (PFS)
time frame: 2 years
description: efficacy evaluation
measure: Overall survival (OS)
time frame: 2 years
description: efficacy evaluation
measure: Number of Participants with positive anti drug antibody (ADA)
time frame: 2 years
description: safety evaluation
measure: Number of Participants with positive neutralizing antibody (Nab)
time frame: 2 years
description: safety evaluation
arm group label: MW11 injection
arm group type: Experimental
description: 1, 3, 10 mg/kg and maybe an additional fixed dose (e.g., to evaluate 200 mg or other fixed dose as RP2D). The drug is scheduled to be administrated Q3W.
intervention type: Drug
intervention name: PD-1 monoclonal antibody
description: The enrollment mainly depends on "3+3" principle. A total of 3 or 4 dose groups will be evaluated during the dose escalation period: 1, 3, 10 mg/kg, and maybe an additional fixed dose (e.g., to evaluate 200 mg or other fixed dose as RP2D). The drug is scheduled to be administrated Q3W
arm group label: MW11 injection
other name: MW11 injection
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Suxia Luo, professor
role: Principal Investigator
affiliation: Henan Cancer Hospital
last name: Shan An
phone: 13613865536
email: watermelonas@163.com
facility: 
status: Recruiting
contact: 
country: China
responsible party type: Sponsor
mesh term: Neoplasms
mesh term: Antibodies
mesh term: Antibodies, Monoclonal