<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/NCT03808857</url>
  </required_header>
  <id_info>
    <org_study_id>Gxplore-008</org_study_id>
    <nct_id>NCT03808857</nct_id>
  </id_info>
  <brief_title>A Study in Recurrent or Metastatic Cervical Cancer Patients With PD-L1 Positive</brief_title>
  <official_title>Phase II Clinical Study to Evaluate the Efficacy and Safety of GB226 in Treatment of Recurrent or Metastatic Cervical Cancer Patients With PD-L1 Positive Who Failed in Platinum-based Chemotherapy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Genor Biopharma Co., Ltd.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Genor Biopharma 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 study is a multi-center, prospective, open-label, single-arm phase II clinical study to&#xD;
      evaluate the efficacy, safety and immunogenicity of GB226 in treatment of recurrent or&#xD;
      metastatic cervical cancer patients with PD-L1 positive who failed in platinum-based&#xD;
      chemotherapy.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">May 23, 2019</start_date>
  <completion_date type="Anticipated">July 2022</completion_date>
  <primary_completion_date type="Anticipated">December 2021</primary_completion_date>
  <phase>Phase 2</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>Objective response rate, ORR</measure>
    <time_frame>2 years</time_frame>
    <description>To evaluate the efficacy of GB226 as defined by objective response rate, in patients with recurrent or metastatic cervical cancer.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Disease control rate,DCR</measure>
    <time_frame>2 years</time_frame>
    <description>To evaluate the efficacy of GB226 as defined by overall response rate, in patients with recurrent or metastatic cervical cancer.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to response, TTR</measure>
    <time_frame>2 years</time_frame>
    <description>To evaluate the efficacy of GB226 as defined by time to response in patients with recurrent or metastatic cervical cancer.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of response, DOR</measure>
    <time_frame>2 years</time_frame>
    <description>To evaluate the duration of response (DOR) of GB242 in patients with recurrent or metastatic cervical cancer.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression-free survival, PFS</measure>
    <time_frame>2 years</time_frame>
    <description>To evaluate the efficacy of GB226 as defined by progression-free survival, in patients with recurrent or metastatic cervical cancer.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival, OS</measure>
    <time_frame>2 years</time_frame>
    <description>To evaluate the duration from the first administration to death because of any reason in patients with recurrent or metastatic cervical cancer.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">80</enrollment>
  <condition>Cervical Cancer</condition>
  <arm_group>
    <arm_group_label>GB226</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Geptanolimab Injection,3mg/kg once per 2 weeks</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>GB226</intervention_name>
    <description>GB226 is administrated at the dose of 3mg/kg, once per 2 weeks (±3 days), and distributed in 100ml of 0.9% sodium chloride solution. The concentration of GB226 shall be strictly controlled at 1mg/ml~10mg/ml, the duration is 60 min (±10 min) for the first infusion of the drug, and can be reduced to 30 min (±10 min) for the subsequent infusion of the drug if there is infusion related adverse reaction.</description>
    <arm_group_label>GB226</arm_group_label>
    <other_name>Geptanolimab</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  1. Age ≥18 years old;&#xD;
&#xD;
          -  2. Understand the steps and contents of the study, and voluntary to sign the written&#xD;
             informed consent form;&#xD;
&#xD;
          -  3. Recurrent or metastatic cervical cancer diagnosed by histology or cytology;&#xD;
&#xD;
          -  4. Recurrent or metastatic after receiving at least first-line platinum base&#xD;
             chemotherapy (≥1 period) (Subjects who progress or recur during or within 6 months&#xD;
             after the end of platinum-based new adjuvant or adjuvant chemotherapy are deemed to&#xD;
             have received first-line treatment);&#xD;
&#xD;
          -  5. Subjects must have at least one measurable target lesion (lesion with longest&#xD;
             diameter ≥10mm, or lymph node with short diameter ≥15mm) tested by CT or MRI according&#xD;
             to the RECIST 1.1 criteria;&#xD;
&#xD;
          -  6. Expected survival period ≥3 months;&#xD;
&#xD;
          -  7. ECOG score 0-1 point;&#xD;
&#xD;
          -  8. Subjects shall provide sufficient formalin fixed paraffin embedded (FFPE) specimens&#xD;
             or sections prepared from tumor archived tissues or fresh tissues that meet the test&#xD;
             criteria, and are willing to perform biopsy of tumor tissues for test of PD-L1 if&#xD;
             needed. The archived tissue shall be a representative tumor specimen within three&#xD;
             years, or unstained serial sections (not less than 4) of the newly cut FFPE tumor&#xD;
             tissue within six months, and the above-mentioned specimens related pathology reports&#xD;
             shall also be provided. Fresh tissue specimens can be obtained by resection, core&#xD;
             needle biopsy, excision, stamping or forceps biopsy (more than 100 tumor cells must be&#xD;
             guaranteed); samples are not accepted for fine needle puncture and liquid based&#xD;
             cytology test (TCT) (namely, the samples lack of complete tissue structure thus to&#xD;
             only provide cell suspension and/or cell smear); decalcified bone metastatic tumor&#xD;
             samples are not accepted. For core-needle biopsy specimens, at least 3 single paraffin&#xD;
             embedded specimens shall be submitted for evaluation. For patients with PD-L1 negative&#xD;
             in initially archived tumor tissue samples, biopsy can be performed during screening&#xD;
             with the patients' consent to provide fresh tissue prepared paraffin blocks or&#xD;
             sections for retest of PD-L1 status, and the qualification of this study is met if any&#xD;
             kind of tumor tissue samples have positive results;&#xD;
&#xD;
          -  9. The values of laboratory tests performed during screening shall meet the following&#xD;
             criteria:&#xD;
&#xD;
               -  Blood routine test (No blood transfusion within 14 days before test, no use of&#xD;
                  G-CSF, no use of drug correction);&#xD;
&#xD;
                    1. Hemoglobin (HGB) ≥90 g/L;&#xD;
&#xD;
                    2. Absolute neutrophil count (ANC) ≥1.5×109/L;&#xD;
&#xD;
                    3. Blood platelet (PLT) ≥100×109/L；&#xD;
&#xD;
               -  Biochemical test&#xD;
&#xD;
                    1. Total bilirubin (TBIL) ≤1.5× Upper limit of normal (ULN) (Gilbert syndrome&#xD;
                       allowance ≤5×ULN);&#xD;
&#xD;
                    2. Alanine transaminase (ALT) and aspartate aminotransferase (AST) ≤2.5×ULN (if&#xD;
                       liver metastasis exists, ALT and AST ≤5×ULN);&#xD;
&#xD;
                    3. Serum creatinine (Cr) ≤1.5×ULN or endogenous creatinine clearance rate&#xD;
                       ≥50mL/min (Cockcroft-Gault formula);&#xD;
&#xD;
          -  10. Thyroid function index: Thyroid-stimulating hormone (TSH) and free thyroxine&#xD;
             (FT3/FT4) are in normal range; Subjects could be enrolled if FT3/FT4 in the normal&#xD;
             range,and TSH without the normal range;&#xD;
&#xD;
          -  11. Women who are not pregnant within 7 days before administration of study drug;&#xD;
             women in child-bearing period shall agree to use medically approved effective&#xD;
             contraception throughout the whole study period and within 6 months after completion&#xD;
             of study;&#xD;
&#xD;
          -  12. Subjects can be followed up on schedule, able to communicate well with the&#xD;
             investigator, and able to complete the study in accordance with the requirements of&#xD;
             this study.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  1. Patient with other previous malignancies (except the cured skin basal cell&#xD;
             carcinoma or squamous cell carcinoma) shall not participate in this study unless she&#xD;
             experiences a &quot;complete response&quot; for at least 5 years before enrollment, and it is&#xD;
             estimated that no other anti-tumor therapy will be required during the whole study;&#xD;
&#xD;
          -  2. Active central nervous system (CNS) metastasis, including symptomatic brain&#xD;
             metastasis or meningeal metastasis or spinal cord compression, etc.; asymptomatic&#xD;
             brain metastasis can be enrolled (no progression within at least 4 weeks after&#xD;
             radiotherapy and/or no postoperative neurological symptoms or signs, no need for&#xD;
             treatment with glucocorticoid, anticonvulsant drugs or mannitol);&#xD;
&#xD;
          -  3. Experienced systemic chemotherapy, radial/extensive radiotherapy, targeted therapy,&#xD;
             anti-tumor biotherapy (e.g. tumor vaccine, cytokine or growth factor, etc.) within 28&#xD;
             days before administration of study drug, or experienced local palliative radiotherapy&#xD;
             within 14 days;&#xD;
&#xD;
          -  4. Less than 14 days before the study was conducted with major surgery or severe&#xD;
             trauma(Subjects could be enrolled ,except for skin or percutaneous biopsy with local&#xD;
             anesthesia ,and recovered within 7 days);&#xD;
&#xD;
          -  5. Received corticosteroids (prednisone &gt; 10 mg/day or equivalent dose) or other&#xD;
             immunosuppressive drugs within 14 days before administration of study drug;&#xD;
&#xD;
          -  6. Have active, known history of autoimmune disease, including but not limited to&#xD;
             systemic lupus erythematosus, psoriasis, rheumatoid arthritis, inflammatory bowel&#xD;
             disease, Hashimoto's thyroiditis, etc. other than type I diabetes mellitus,&#xD;
             hypothyroidism controlled only by hormone replacement therapy, skin diseases (e.g.&#xD;
             vitiligo) requiring no systemic treatment and controlled celiac disease;&#xD;
&#xD;
          -  7. Complications requiring the treatment with immunosuppressive drugs, or&#xD;
             complications requiring systemic treatment at the dose with immunosuppressive effects&#xD;
             (prednisone &gt; 10mg/day or equivalent dose to similar drug); in the absence of active&#xD;
             autoimmune disease, inhaling or local administration of steroids and prednisone at&#xD;
             dose &gt; 10mg/day or equivalent dose to similar drug are allowed;&#xD;
&#xD;
          -  8. Uncontrolled hypertension (systolic pressure &gt;140 mmHg and/or diastolic pressure &gt;&#xD;
             90 mmHg) or pulmonary hypertension or unstable angina pectoris; underwent myocardial&#xD;
             infarction, bypass or stent surgery within 6 months before administration; have a&#xD;
             history of grade 3-4 chronic heart failure that meets the criteria of New York Heart&#xD;
             Association (NYHA); Valvular heart disease with clinical significance; severe&#xD;
             arrhythmia requiring treatment, including QTc interval ≥ 470 ms (calculate by&#xD;
             Fridericia formula); left ventricular ejection fraction (LVEF) &lt; 50%; Cerebral&#xD;
             vascular accident (CVA) or transient ischemic attach (TIA) within 6 months before&#xD;
             administration, etc.;&#xD;
&#xD;
          -  9. Complicated with other serious medical disease, including but not limited to&#xD;
             uncontrolled diabetes mellitus, active gastrointestinal ulcers, active hemorrhage,&#xD;
             etc.;&#xD;
&#xD;
          -  10. Subjects suffering from active infections that require systemic treatment;&#xD;
&#xD;
          -  11. Patients with previous or present infection with active tuberculosis;&#xD;
&#xD;
          -  12. Have the previous history of interstitial pulmonary disease;&#xD;
&#xD;
          -  13. Uncontrollable symptomatic dropsy of serous cavity, such as ascites, pleural&#xD;
             effusion or pericardial effusion;&#xD;
&#xD;
          -  14. Human immunodeficiency virus antibody (HIV-Ab) and Treponema pallidum positive;&#xD;
             hepatitis C antibody (HCV-Ab) positive, and hepatitis C virus RNA quantification &gt; the&#xD;
             upper limit of normal of test unit; hepatitis B surface antigen (HBsAg) positive, and&#xD;
             hepatitis B virus test value &gt; the upper limit of normal of test unit;&#xD;
&#xD;
          -  15. Adverse events caused by previous treatment have not recovered to grade 1 or below&#xD;
             (CTCAE5.0) (except the grade 2 neurotoxicity caused by alopecia and&#xD;
             chemotherapeutics);&#xD;
&#xD;
          -  16. Have been treated with anti PD-1 antibody, anti PD-L1 antibody, anti PD-L2&#xD;
             antibody or anti CTLA-4 antibody (or any other antibodies acting on T cell&#xD;
             co-stimulation or checkpoint pathway);&#xD;
&#xD;
          -  17. Used live vaccine or attenuated vaccine within 28 days before administration of&#xD;
             study drug;&#xD;
&#xD;
          -  18. Used other study drugs or study devices within 30 days before administration of&#xD;
             study drug;&#xD;
&#xD;
          -  19. Patients with a history of drug addiction or drug abuse upon inquiry;&#xD;
&#xD;
          -  20. Patients with previous definite neurological or mental disorders, such as&#xD;
             epilepsy, dementia, poor compliance;&#xD;
&#xD;
          -  21.Lactating women who do not agree to stop breastfeeding ;&#xD;
&#xD;
          -  22. Known allergy to recombinant human PD-1 monoclonal antibody or any of its&#xD;
             excipients; known history of allergic disease or severe allergic constitution;&#xD;
&#xD;
          -  23. Patients who are not suitable for participating in this study due to other various&#xD;
             reasons upon investigator's opinions.&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Lingying Wu, Doctor</last_name>
    <role>Principal Investigator</role>
    <affiliation>Cancer Institute and Hospital, Chinese Academy of Medical Sciences</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Shawn Yu, master</last_name>
    <phone>86-010-65260820</phone>
    <email>shawn.yu@genorbio.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>National Cancer Center/Cancer Hospital,Chinese Academy of Medical Sciences and Peking Union Medical College</name>
      <address>
        <city>Beijing</city>
        <state>Beijing</state>
        <zip>100021</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Lingying Wu</last_name>
      <phone>0086-010-67781331,china</phone>
      <email>wulingying@csco.org.cn</email>
    </contact>
    <investigator>
      <last_name>Wu Lingying, Medical PhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>March 2021</verification_date>
  <study_first_submitted>December 27, 2018</study_first_submitted>
  <study_first_submitted_qc>January 16, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 18, 2019</study_first_posted>
  <last_update_submitted>March 2, 2021</last_update_submitted>
  <last_update_submitted_qc>March 2, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">March 3, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>recurrent Metastatic Cervical Cancer</keyword>
  <keyword>platinum</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Uterine Cervical Neoplasms</mesh_term>
  </condition_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/NCT03808857
org study id: Gxplore-008
nct id: NCT03808857
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
This study is a multi-center, prospective, open-label, single-arm phase II clinical study to
      evaluate the efficacy, safety and immunogenicity of GB226 in treatment of recurrent or
      metastatic cervical cancer patients with PD-L1 positive who failed in platinum-based
      chemotherapy.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Objective response rate, ORR
time frame: 2 years
description: To evaluate the efficacy of GB226 as defined by objective response rate, in patients with recurrent or metastatic cervical cancer.
measure: Disease control rate,DCR
time frame: 2 years
description: To evaluate the efficacy of GB226 as defined by overall response rate, in patients with recurrent or metastatic cervical cancer.
measure: Time to response, TTR
time frame: 2 years
description: To evaluate the efficacy of GB226 as defined by time to response in patients with recurrent or metastatic cervical cancer.
measure: Duration of response, DOR
time frame: 2 years
description: To evaluate the duration of response (DOR) of GB242 in patients with recurrent or metastatic cervical cancer.
measure: Progression-free survival, PFS
time frame: 2 years
description: To evaluate the efficacy of GB226 as defined by progression-free survival, in patients with recurrent or metastatic cervical cancer.
measure: Overall survival, OS
time frame: 2 years
description: To evaluate the duration from the first administration to death because of any reason in patients with recurrent or metastatic cervical cancer.
arm group label: GB226
arm group type: Experimental
description: Geptanolimab Injection,3mg/kg once per 2 weeks
intervention type: Biological
intervention name: GB226
description: GB226 is administrated at the dose of 3mg/kg, once per 2 weeks (±3 days), and distributed in 100ml of 0.9% sodium chloride solution. The concentration of GB226 shall be strictly controlled at 1mg/ml~10mg/ml, the duration is 60 min (±10 min) for the first infusion of the drug, and can be reduced to 30 min (±10 min) for the subsequent infusion of the drug if there is infusion related adverse reaction.
arm group label: GB226
other name: Geptanolimab
criteria: 
gender: Female
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Lingying Wu, Doctor
role: Principal Investigator
affiliation: Cancer Institute and Hospital, Chinese Academy of Medical Sciences
last name: Shawn Yu, master
phone: 86-010-65260820
email: shawn.yu@genorbio.com
facility: 
status: Recruiting
contact: 
investigator: 
country: China
responsible party type: Sponsor
mesh term: Uterine Cervical Neoplasms