<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/NCT03228836</url>
  </required_header>
  <id_info>
    <org_study_id>CIBI308D201</org_study_id>
    <nct_id>NCT03228836</nct_id>
  </id_info>
  <brief_title>Efficacy and Safety Evaluation of IBI308 in Patients With Extranodal NK/T Cell Lymphoma Patients</brief_title>
  <acronym>ORIENT-4</acronym>
  <official_title>Efficacy and Safety Evaluation of IBI308 in Patients With Relapsed/Refractory Extranodal NK/T Cell Lymphoma, Nasal Type: a Multicenter, Single Arm, Phase 2 Study (ORIENT-4)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Innovent Biologics (Suzhou) Co. Ltd.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Innovent Biologics (Suzhou) 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 phase II study. Efficacy and safety evaluation of IBI308 in patients with&#xD;
      relapsed/refractory extranodal NK/T cell lymphoma, nasal type: a multicenter, single arm.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Extranodal NK/T cell lymphoma, nasal type(ENKTL) accounts for about 6% of all lymphomas in&#xD;
      china. Epstein Barr virus (EBV) infection is found in all cases of ENKTL and maybe plays an&#xD;
      important pathogenetic role.&#xD;
&#xD;
      Conventional anthrocycline-based regimens are not preferred to be used in ENKTL because of&#xD;
      high p-glycoprotein expression. ORR of L-asparaginase based regimens is about 80% and no&#xD;
      salvage regimens are recommended in ENKTL so far after failure of L-asparaginase based&#xD;
      regimen.&#xD;
&#xD;
      Recently, a phase II clinical trial result demonstrated high ORR of anti-PD-1 antibody&#xD;
      treatment in ENKTL.IBI308, a humanized monoclonal antibody (mAb) directly against PD-1, is&#xD;
      investigated in this phase II Chinese ENKTL clinical trial.&#xD;
&#xD;
      Additionally the correlation between PD-L1 expression and the response to IBI308 treatment in&#xD;
      Chinese ENKTL subjects will also be assessed.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 23, 2017</start_date>
  <completion_date type="Actual">February 28, 2020</completion_date>
  <primary_completion_date type="Actual">February 28, 2020</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) Before First PD</measure>
    <time_frame>Up to ~30 months (through database cut-off date of 28-February-2020)</time_frame>
    <description>The tumor assessment is according to Lugano 2014 Criteria and then International Working Group (IWG) 2007 Criteria after 24 weeks. Objective response is defined as best overall response (CR or PR) across all assessment time points during the period from enrollment to termination of trial treatment (per Lugano 2014 criteria during intial 24 weeks, per IWG 2007 criteria after 24 weeks). The primary efficacy endpoint is ORR evaluated using the 2014 Lugano Criteria before first progression disease (PD).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Progression Free Survival (PFS)</measure>
    <time_frame>Up to ~30 months (through database cut-off date of 28-February-2020)</time_frame>
    <description>PFS was defined as the time from the first dose to the first documented progressive disease (PD) per Lugano 2014 or death due to any cause, whichever occurred first. Participates who neither progress nor die were censored at the date of their last tumor imaging evaluation. Participates who did not have any tumor imaging evaluation after baseline were censored on the date of enrollment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of Response (DOR)</measure>
    <time_frame>Up to ~30 months (through database cut-off date of 28-February-2020)</time_frame>
    <description>DOR was defined as the time from first date of response to first PD per Lugano 2014 or death. Subjects who neither progress nor die were censored at the date of their last tumor imaging evaluation.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">28</enrollment>
  <condition>Effect of Drugs</condition>
  <arm_group>
    <arm_group_label>Sintilimab (IBI308)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Sintilimab</intervention_name>
    <description>Sintilimab (IBI308) 200mg IV Q3W</description>
    <arm_group_label>Sintilimab (IBI308)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Inclusion Criteria&#xD;
&#xD;
          1. Histologically confirmed ENKL-NT.&#xD;
&#xD;
          2. Relapsed or refractory ENKTL-NT. Being relapsed is defined as presence of new lesions&#xD;
             at the primary location or other sites after achieving CR; being refractory is defined&#xD;
             as any one of the followings: PD after 2 treatment cycles, PR not achieved after 4&#xD;
             treatment cycles, or CR not achieved after 6 treatment cycles. Patients who do not&#xD;
             response or patients with relapsed disease or PD after autologous stem cell&#xD;
             transplantation can enroll.&#xD;
&#xD;
          3. Must have been treated with asparaginase-based regimen (radiotherapy must be performed&#xD;
             for stage I/II disease).&#xD;
&#xD;
          4. Long axis of a lesion &gt; 15 mm or 18FDG-PET uptake by lesion.&#xD;
&#xD;
          5. Eastern Cooperative Oncology Group Performance Status (ECOG PS) scores of 0-2.&#xD;
&#xD;
          6. Signed the inform consent form (ICF) and able to comply with the scheduled follow-up&#xD;
             visits and related procedures required in the protocol.&#xD;
&#xD;
          7. Between the ages of ≥18 to ≤70 years.&#xD;
&#xD;
          8. Life expectancy≥ 12 weeks.&#xD;
&#xD;
          9. Patients (female patients at childbearing age or male patients whose partners are at&#xD;
             childbearing age) must take effective contraceptive measures during the entire course&#xD;
             of the trial and within 90 days since the last dose of treatment.&#xD;
&#xD;
         10. Adequate organs and bone marrow functions, as defined below: Count of whole blood&#xD;
             cells: absolute neutrophil count (ANC) ≥1.0×10^9/L, platelets (PLTs) count ≥&#xD;
             50×10^9/L, hemoglobin (HGB) ≥ 8.0 g/L; granulocyte colony-stimulating factor, PLT, or&#xD;
             red blood cell (RBC) transfusion has not been performed within 7 days prior to the&#xD;
             test. Hepatic function: total bilirubin (TBIL) ≤ 1.5×upper limit of normal (ULN),&#xD;
             alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN. Renal&#xD;
             function:serum creatinine (Cr) ≤ 1.5 × ULN. Thyroid function: normal thyroid&#xD;
             stimulating hormone (TSH) at baseline, or abnormal TSH at baseline with normal&#xD;
             thiiodothronine (T3)/thiiodothronine (T4) and no symptoms.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Patients with aggressive NK cell leukemia.&#xD;
&#xD;
          2. Patients with primary or secondary central nervous system (CNS) lymphoma.&#xD;
&#xD;
          3. Patients with severe hemophagocytic syndrome at initial diagnosis of ENKTL-NT.&#xD;
&#xD;
          4. Patients with pulmonary great vessel invasion.&#xD;
&#xD;
          5. Previous exposure to any anti-PD-1, anti-PD-L1, or anti-CTLA-4 antibodies.&#xD;
&#xD;
          6. Enrolled in another interventional clinical study, unless only involved in an&#xD;
             observational study (non-interventional) or in the follow-up phase of an&#xD;
             interventional study.&#xD;
&#xD;
          7. Received any investigational drug within 4 weeks prior to the first dose of study&#xD;
             treatment.&#xD;
&#xD;
          8. The last dose of radiation or anti-tumor therapy (chemotherapy, targeted therapy or&#xD;
             tumor embolization) was within 3 weeks prior to receiving the first dose of study&#xD;
             treatment; the last dose of nitrosourea or mitomycin C treatment was within 6 weeks&#xD;
             prior to receiving the first dose of study treatment.&#xD;
&#xD;
          9. Received immunosuppressants within 4 weeks prior to the first dose of study treatment,&#xD;
             excluding local glucocorticoids administered by nasal, inhaled, or other topical&#xD;
             routes, or systemic glucocorticoids of physiological doses (no more than 10 mg/day of&#xD;
             prednisone or equivalents).&#xD;
&#xD;
         10. Received any live attenuated vaccine within 4 weeks prior to the first dose of study&#xD;
             treatment, or is scheduled to receive live attenuated vaccine during the study period.&#xD;
&#xD;
         11. Received major surgery (craniotomy, thoracotomy, or laparotomy) within 4 weeks prior&#xD;
             to the first dose of study treatment, or has unhealed wounds, ulcers, or fractures.&#xD;
&#xD;
         12. Active, known, or suspected autoimmune disease (see Appendix 6) or previous medical&#xD;
             history of these diseases within 2 years (patients with vitiligo, psoriasis, alopecia,&#xD;
             or Graves' disease not requiring systemic treatment, hypothyroidism only requiring&#xD;
             thyroid replacement, or type I diabetes only requiring insulin can enroll).&#xD;
&#xD;
         13. Known history of primary immunodeficiency diseases.&#xD;
&#xD;
         14. Known active pulmonary tuberculosis.&#xD;
&#xD;
         15. Known history of allogeneic organ transplantation or allogeneic hem atopoietic stem&#xD;
             cell transplantation.&#xD;
&#xD;
         16. Known to be allergic to any ingredients of monoclonal antibodies.&#xD;
&#xD;
         17. Uncontrolled concurrent diseases including but not limited to:&#xD;
&#xD;
             HIV-infected patients (positive anti-HIV antibody). Active or poorly controlled severe&#xD;
             infections. Symptomatic congestive heart failure (NYHA Class III-IV) or symptomatic or&#xD;
             poorly controlled arrhythmia.&#xD;
&#xD;
             Uncontrolled hypertension (systolic blood pressure ≥ 160 mmHg or diastolic blood&#xD;
             pressure ≥ 100 mmHg) despite of standard treatment.&#xD;
&#xD;
             Any arterial thromboembolic events occurred within 6 months prior to enrollment,&#xD;
             including myocardial infarction, unstable angina, cerebrovascular accident, or&#xD;
             transient cerebral ischemic attack.&#xD;
&#xD;
             Life-threatening hemorrhagic events or grade 3-4 gastrointestinal/variceal hemorrhage&#xD;
             requiring blood transfusion, endoscopy, or surgical treatment within 3 months prior to&#xD;
             enrollment.&#xD;
&#xD;
             History of deep venous thrombosis, pulmonary embolism, or other serious thromboembolic&#xD;
             events within 3 months prior to enrollment (implantable port or catheter-related&#xD;
             thrombosis, or superficial venous thrombosis are not considered as serious&#xD;
             thromboembolisms).&#xD;
&#xD;
             Uncontrolled metabolic disorders, non-malignant organ or systemic diseases, or&#xD;
             cancer-related secondary diseases that may lead to higher medical risks and/or&#xD;
             survival evaluation uncertainties.&#xD;
&#xD;
             Hepatic encephalopathy, hepatorenal syndrome, or cirrhosis with Child-Pugh grade B or&#xD;
             C.&#xD;
&#xD;
             Bowel obstruction or history of the following diseases: inflammatory bowel disease or&#xD;
             extensive bowel resection (partial colectomy or extensive small bowel resection&#xD;
             accompanied with chronic diarrhea), Crohn's disease, and ulcerative colitis.&#xD;
&#xD;
             Acute or chronic diseases, psychiatric disorders, or laboratory abnormalities that may&#xD;
             lead to the following consequences: increased investigational drug-related risks, or&#xD;
             interference with interpreting trial results, and considered ineligible for&#xD;
             participating in the trial by the investigators.&#xD;
&#xD;
         18. Known acute or chronic active hepatitis B (chronic HBV carriers or inactive&#xD;
             HBsAg-positive patients can enroll if the HBV DNA &lt; 1×10^3 copies/mL), or acute or&#xD;
             chronic active hepatitis C (patients with negative HCV antibody can enroll; HCV RNA&#xD;
             test is required for patients with positive HCV antibody, those test negative can&#xD;
             enroll).&#xD;
&#xD;
         19. History of GI perforation and/or fistula without radical treatment within 6 months&#xD;
             prior to the enrollment.&#xD;
&#xD;
         20. Known interstitial lung disease.&#xD;
&#xD;
         21. Clinically uncontrollable third spacing, such as pleural effusion and ascites that&#xD;
             cannot be controlled by drainage or other methods prior to enrollment.&#xD;
&#xD;
         22. History of other primary malignant tumors, excluding:&#xD;
&#xD;
             History of radical treatment for malignant tumors with no evidence of tumor recurrence&#xD;
             for more than 5 years prior to enrollment and with a very low risk of recurrence.&#xD;
&#xD;
             Adequately treated nonmelanoma skin cancer or lentigo maligna with no signs of disease&#xD;
             recurrence.&#xD;
&#xD;
             Adequately treated carcinoma in situ with no signs of disease recurrence.&#xD;
&#xD;
         23. Pregnant or breastfeeding female patients.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jian-yong Li, Master</last_name>
    <role>Principal Investigator</role>
    <affiliation>The First Affiliated Hospital with Nanjing Medical University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Jiangsu Provincial Hospital</name>
      <address>
        <city>Nanjing</city>
        <state>Jiangsu</state>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>December 2020</verification_date>
  <study_first_submitted>July 22, 2017</study_first_submitted>
  <study_first_submitted_qc>July 22, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">July 25, 2017</study_first_posted>
  <results_first_submitted>November 18, 2020</results_first_submitted>
  <results_first_submitted_qc>November 18, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">December 17, 2020</results_first_posted>
  <last_update_submitted>December 20, 2020</last_update_submitted>
  <last_update_submitted_qc>December 20, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">January 12, 2021</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>Lymphoma, T-Cell</mesh_term>
    <mesh_term>Lymphoma, Extranodal NK-T-Cell</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>July 8, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/36/NCT03228836/Prot_001.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>February 28, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/36/NCT03228836/SAP_002.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Sintilimab (IBI308)</title>
          <description>Participants with relapsed or refractory ENKTL-NT were enrolled to receive sintilimab (IBI308) 200mg intravenous infusion (IV) every 3 weeks (Q3W).</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="28"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Treated</title>
              <participants_list>
                <participants group_id="P1" count="28"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="11"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="17"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Death</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Physician Decision</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Disease Progression</title>
              <participants_list>
                <participants group_id="P1" count="7"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Other</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Sintilimab (IBI308)</title>
          <description>Participants with relapsed or refractory ENKTL-NT were enrolled to receive sintilimab (IBI308) 200mg IV Q3W.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="28"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="27"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="40.32" spread="12.67"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="11"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="17"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="28"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>China</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="28"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Objective Response Rate (ORR) Before First PD</title>
        <description>The tumor assessment is according to Lugano 2014 Criteria and then International Working Group (IWG) 2007 Criteria after 24 weeks. Objective response is defined as best overall response (CR or PR) across all assessment time points during the period from enrollment to termination of trial treatment (per Lugano 2014 criteria during intial 24 weeks, per IWG 2007 criteria after 24 weeks). The primary efficacy endpoint is ORR evaluated using the 2014 Lugano Criteria before first progression disease (PD).</description>
        <time_frame>Up to ~30 months (through database cut-off date of 28-February-2020)</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Sintilimab (IBI308)</title>
            <description>Participants with relapsed or refractory ENKTL-NT were enrolled to receive sintilimab (IBI308) 200mg IV Q3W.</description>
          </group>
        </group_list>
        <measure>
          <title>Objective Response Rate (ORR) Before First PD</title>
          <description>The tumor assessment is according to Lugano 2014 Criteria and then International Working Group (IWG) 2007 Criteria after 24 weeks. Objective response is defined as best overall response (CR or PR) across all assessment time points during the period from enrollment to termination of trial treatment (per Lugano 2014 criteria during intial 24 weeks, per IWG 2007 criteria after 24 weeks). The primary efficacy endpoint is ORR evaluated using the 2014 Lugano Criteria before first progression disease (PD).</description>
          <units>Percentage of Participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="28"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="60.7" lower_limit="40.6" upper_limit="78.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Progression Free Survival (PFS)</title>
        <description>PFS was defined as the time from the first dose to the first documented progressive disease (PD) per Lugano 2014 or death due to any cause, whichever occurred first. Participates who neither progress nor die were censored at the date of their last tumor imaging evaluation. Participates who did not have any tumor imaging evaluation after baseline were censored on the date of enrollment.</description>
        <time_frame>Up to ~30 months (through database cut-off date of 28-February-2020)</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Sintilimab (IBI308)</title>
            <description>Participants with relapsed or refractory ENKTL-NT were enrolled to receive sintilimab (IBI308) 200mg IV Q3W.</description>
          </group>
        </group_list>
        <measure>
          <title>Progression Free Survival (PFS)</title>
          <description>PFS was defined as the time from the first dose to the first documented progressive disease (PD) per Lugano 2014 or death due to any cause, whichever occurred first. Participates who neither progress nor die were censored at the date of their last tumor imaging evaluation. Participates who did not have any tumor imaging evaluation after baseline were censored on the date of enrollment.</description>
          <units>Days</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="28"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="104.0" lower_limit="45.0" upper_limit="419.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Duration of Response (DOR)</title>
        <description>DOR was defined as the time from first date of response to first PD per Lugano 2014 or death. Subjects who neither progress nor die were censored at the date of their last tumor imaging evaluation.</description>
        <time_frame>Up to ~30 months (through database cut-off date of 28-February-2020)</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Sintilimab (IBI308)</title>
            <description>Participants with relapsed or refractory ENKTL-NT were enrolled to receive sintilimab (IBI308) 200mg IV Q3W.</description>
          </group>
        </group_list>
        <measure>
          <title>Duration of Response (DOR)</title>
          <description>DOR was defined as the time from first date of response to first PD per Lugano 2014 or death. Subjects who neither progress nor die were censored at the date of their last tumor imaging evaluation.</description>
          <units>Days</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="28"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="126.0" lower_limit="64.0" upper_limit="463.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Up to ~30 months (through database cut-off date of 28-February-2020)</time_frame>
      <desc>Safety Population: all the participants who received at least one dose of the investigational drug.</desc>
      <group_list>
        <group group_id="E1">
          <title>Sintilimab (IBI308)</title>
          <description>Sintilimab (IBI308) 200mg IV Q3W</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>CTCAE (4.03)</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="28"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Gastrointestinal haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Pancreatitis acute</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="28"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Disease progression</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="28"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Immune system disorders</title>
            <event_list>
              <event>
                <sub_title>Anaphylactic shock</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="28"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Localised infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="28"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Diabetic ketoacidosis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="28"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Intervertebral disc disorder</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="28"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>CTCAE (4.03)</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="28" subjects_at_risk="28"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anaemia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Lymphadenitis</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="28"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Myocardial ischaemia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Ventricular extrasystoles</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="28"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Endocrine disorders</title>
            <event_list>
              <event>
                <sub_title>Autoimmune thyroiditis</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Hypothyroidism</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="28"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Gastritis</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Mouth ulceration</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="28"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Face oedema</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Pain</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" subjects_affected="13" subjects_at_risk="28"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Enterovirus infection</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Gingivitis</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Pharyngitis</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Sinusitis</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="28"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Blood albumin decreased</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Blood alkaline phosphatase increased</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Blood bilirubin increased</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Blood glucose increased</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Blood lactate dehydrogenase increased</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Blood thyroid stimulating hormone increased</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>C-reactive protein increased</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Electrocardiogram abnormal</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Gamma-glutamyltransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Globulins decreased</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Globulins increased</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Haemoglobin decreased</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Haemoglobin urine present</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Lipase increased</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Lymphocyte count decreased</sub_title>
                <counts group_id="E1" subjects_affected="17" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Neutrophil count decreased</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Platelet count decreased</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Protein total decreased</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Protein urine present</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Red blood cells urine positive</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Thyroid function test abnormal</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Thyroxine free decreased</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Thyroxine increased</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Tri-iodothyronine free decreased</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Urine ketone body present</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Weight decreased</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>White blood cell count decreased</sub_title>
                <counts group_id="E1" subjects_affected="14" subjects_at_risk="28"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Diabetes mellitus</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Electrolyte imbalance</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Hypokalaemia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Hypoproteinaemia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="28"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Myalgia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="28"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="28"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Nephrolithiasis</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="28"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Nasal obstruction</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Oropharyngeal pain</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="28"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Pruritus</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Rash</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="28"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Yi Bo</name_or_title>
      <organization>Innovent Biologics (Suzhou) Co., Ltd. (seal)</organization>
      <phone>+8613382419112</phone>
      <email>jessica.yi@innoventbio.com</email>
    </point_of_contact>
  </clinical_results>
</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/NCT03228836
org study id: CIBI308D201
nct id: NCT03228836
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This is phase II study. Efficacy and safety evaluation of IBI308 in patients with
      relapsed/refractory extranodal NK/T cell lymphoma, nasal type: a multicenter, single arm.
Extranodal NK/T cell lymphoma, nasal type(ENKTL) accounts for about 6% of all lymphomas in
      china. Epstein Barr virus (EBV) infection is found in all cases of ENKTL and maybe plays an
      important pathogenetic role.

      Conventional anthrocycline-based regimens are not preferred to be used in ENKTL because of
      high p-glycoprotein expression. ORR of L-asparaginase based regimens is about 80% and no
      salvage regimens are recommended in ENKTL so far after failure of L-asparaginase based
      regimen.

      Recently, a phase II clinical trial result demonstrated high ORR of anti-PD-1 antibody
      treatment in ENKTL.IBI308, a humanized monoclonal antibody (mAb) directly against PD-1, is
      investigated in this phase II Chinese ENKTL clinical trial.

      Additionally the correlation between PD-L1 expression and the response to IBI308 treatment in
      Chinese ENKTL subjects will also be assessed.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Objective Response Rate (ORR) Before First PD
time frame: Up to ~30 months (through database cut-off date of 28-February-2020)
description: The tumor assessment is according to Lugano 2014 Criteria and then International Working Group (IWG) 2007 Criteria after 24 weeks. Objective response is defined as best overall response (CR or PR) across all assessment time points during the period from enrollment to termination of trial treatment (per Lugano 2014 criteria during intial 24 weeks, per IWG 2007 criteria after 24 weeks). The primary efficacy endpoint is ORR evaluated using the 2014 Lugano Criteria before first progression disease (PD).
measure: Progression Free Survival (PFS)
time frame: Up to ~30 months (through database cut-off date of 28-February-2020)
description: PFS was defined as the time from the first dose to the first documented progressive disease (PD) per Lugano 2014 or death due to any cause, whichever occurred first. Participates who neither progress nor die were censored at the date of their last tumor imaging evaluation. Participates who did not have any tumor imaging evaluation after baseline were censored on the date of enrollment.
measure: Duration of Response (DOR)
time frame: Up to ~30 months (through database cut-off date of 28-February-2020)
description: DOR was defined as the time from first date of response to first PD per Lugano 2014 or death. Subjects who neither progress nor die were censored at the date of their last tumor imaging evaluation.
arm group label: Sintilimab (IBI308)
arm group type: Experimental
intervention type: Drug
intervention name: Sintilimab
description: Sintilimab (IBI308) 200mg IV Q3W
arm group label: Sintilimab (IBI308)
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Jian-yong Li, Master
role: Principal Investigator
affiliation: The First Affiliated Hospital with Nanjing Medical University
facility: 
country: China
responsible party type: Sponsor
mesh term: Lymphoma, T-Cell
mesh term: Lymphoma, Extranodal NK-T-Cell
sharing ipd: No
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 