<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/NCT03763149</url>
  </required_header>
  <id_info>
    <org_study_id>CIBI188A102</org_study_id>
    <nct_id>NCT03763149</nct_id>
  </id_info>
  <brief_title>A Study Evaluating the Safety, Tolerability, and Initial Efficacy of Recombinant Human Anti-cluster Differentiation Antigen 47 (CD47) Monoclonal Antibody Injection (IBI188) in Patients With Advanced Malignant Tumors and Lymphomas</brief_title>
  <official_title>A Phase 1a Study Evaluating the Safety, Tolerability, and Initial Efficacy of Recombinant Human Anti-cluster Differentiation Antigen 47 (CD47) Monoclonal Antibody Injection (IBI188) in Patients With Advanced Malignant Tumors and Lymphomas</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>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is an open-label, dose escalation, Phase I study to evaluate the safety, tolerability,&#xD;
      pharmacokinetics and efficacy in patients with advanced malignancies.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The study is composed of two stages: Part 1 Accelerated Titration Phase and Part 2 Dose&#xD;
      Escalation Phase with initial fixed priming dose.&#xD;
&#xD;
      The starting dose for part 1 is 0.1 mg/kg QW, followed by 2 dose cohorts (0.3 mg/kg QW and 1&#xD;
      mg/kg QW). Duration of dose limiting toxicity (DLT) observation is 28 days.&#xD;
&#xD;
      Part 2 will have 4 dose cohorts(3mg/kg QW、10mg/kg QW、20mg/kg QW and 30mg/kg QW). Conventional&#xD;
      3+3 Dose Escalation will be adopted. DLT observation period is 28 days.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">February 19, 2019</start_date>
  <completion_date type="Actual">March 29, 2021</completion_date>
  <primary_completion_date type="Actual">March 29, 2021</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>Number of patients with AEs and SAEs</measure>
    <time_frame>2 years</time_frame>
    <description>To evaluate the safety and tolerability of IBI188 [Adverse events (AEs), Serious Adverse Events (SAE) ]</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics: AUC</measure>
    <time_frame>up to 2 years after enrollment</time_frame>
    <description>The area under the curve (AUC) of serum concentration of the drug after the administration</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics: Cmax</measure>
    <time_frame>up to 2 years after enrollment</time_frame>
    <description>Maximum concentration(Cmax) of the drug after administration</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Immunogenicity: Percentage of ADA positive patients</measure>
    <time_frame>up to 2 years after enrollment</time_frame>
    <description>Number of Anti-Drug Antibodies (ADA) positive patients will be counted and percentage of ADA positive patients will be calculated to evaluate immunogenicity of IBI188.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Preliminary anti-tumor activity of IBI188 (Objective Response Rate)</measure>
    <time_frame>up to 2 years after enrollment</time_frame>
    <description>Objective Response Rate (ORR) is the percentage of Complete Response (CR) plus partial response (PR) assessed by iRECIST v1.1 criteria for solid tumors and Lugano2014 criteria for lymphoma.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">20</enrollment>
  <condition>Advanced Malignancies</condition>
  <arm_group>
    <arm_group_label>IBI188</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Part 1: Accelerated Titration Phase 0.1 mg/kg IV; QW 0.3 mg/kg IV QW; 1 mg/kg IV QW&#xD;
Part 2 : Dose Escalation Phase with initial fixed priming dose Priming dose of 1mg/kg on C1D1 followed by 3 mg/kg IV QW; 10 mg/kg IV QW; 20 mg/kg IV QW; 30 mg/kg IV QW.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>IBI188</intervention_name>
    <description>The study is composed of two stages: Part 1 Accelerated Titration Phase and Part 2 Dose Escalation Phase with initial fixed priming dose.&#xD;
The starting dose for part 1 is 0.1 mg/kg QW, followed by 2 dose cohorts (0.3 mg/kg QW and 1 mg/kg QW). Duration of dose limiting toxicity (DLT) observation is 28 days.&#xD;
Part 2 will have 4 dose cohorts(3mg/kg QW、10mg/kg QW、20mg/kg QW and 30mg/kg QW). Conventional 3+3 Dose Escalation will be adopted. DLT observation period is 28 days.</description>
    <arm_group_label>IBI188</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Able to understand and willing to sign the ICF.&#xD;
&#xD;
          2. Male or female subject above18 years.&#xD;
&#xD;
          3. Histologically/cytologically confirmed, locally advanced unresectable or metastatic&#xD;
             solid tumors and lymphomas that are refractory to standard therapy, or for which no&#xD;
             standard therapy exists.&#xD;
&#xD;
          4. For dose expansion at the RP2D: subject has measurable disease per RECIST v1.1. that&#xD;
             was not in a prior radiation area within past 6 months, unless tumor growth was&#xD;
             documented following radiation. Lymphomas have at least one measurable lesion and&#xD;
             FDG-avid lesion according to the Lugano 2014 criteria.&#xD;
&#xD;
          5. Separate informed consent for subjects who provide archived tissue biopsies for&#xD;
             biomarker testing (Optional).&#xD;
&#xD;
          6. ECOG Performance Status 0 to 1&#xD;
&#xD;
          7. Subjects with life expectancy of ≥ 3 month&#xD;
&#xD;
          8. No herbal/alternative medications within 14 days prior to the first dose of IBI188.&#xD;
&#xD;
          9. Must have adequate organ function, prior to start of IBI188, including the following:&#xD;
&#xD;
               1. Bone marrow reserve: absolute neutrophil count (ANC) ≥ 1.5 x109/L; platelet count&#xD;
                  ≥ 100 x 109/L; hemoglobin ≥ 9 g/dL or ≥ 5.6 mmol/L; Lymphocyte counts ≥ 0.5&#xD;
                  x109/L&#xD;
&#xD;
               2. Hepatic: total bilirubin ≤ 1.5 times the upper limit of normal (ULN), aspartate&#xD;
                  transaminase (AST) and/or alanine aminotransferase (ALT) ≤ 2.5 X ULN (≤5 X ULN if&#xD;
                  with liver involvement)&#xD;
&#xD;
               3. Renal: serum creatinine ≤ 1.5 times the ULN or estimated creatinine clearance&#xD;
                  ≥50mL/min (Cockroft and Gault formula&#xD;
                  [https://www.mdcalc.com/creatinine-clearance-cockcroft-gault-equation]).&#xD;
&#xD;
               4. Coagulation tests INR &lt; 2.0, activated partial thromboplastin time (aPTT) ≤ 1.5 x&#xD;
                  ULN&#xD;
&#xD;
         10. Subjects (women of child-bearing potential and males) must be willing to use viable&#xD;
             contraception method that is deemed effective by the investigator throughout the&#xD;
             treatment period and for at least three months following the last dose of study drug.&#xD;
             Postmenopausal women must have been amenorrhoeic for at least 12 months to be&#xD;
             considered of non-childbearing potential.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Pregnant or nursing females.&#xD;
&#xD;
          2. Any remaining AEs &gt; grade 1 from prior anti-tumor treatment as per CTCAE v5.0, with&#xD;
             exception of the residual hair loss;&#xD;
&#xD;
          3. Received a biologic G-CSF, GM-CSF or erythropoietin within 14 days prior to the first&#xD;
             dose of study drug;&#xD;
&#xD;
          4. Subjects participating in any other interventional clinical study&#xD;
&#xD;
          5. Previous exposure to any anti-CD47 monoclonal antibody or SIRPα antibody.&#xD;
&#xD;
          6. Subjects who had transfusion within 3 weeks&#xD;
&#xD;
          7. Patients who are on anticoagulants and /or require concomitant aspirin or other&#xD;
             nonsteroidal anti-inflammatory medications.&#xD;
&#xD;
          8. Subjects who have a history of documented autoimmune disease, even if not clinically&#xD;
             severe or never treated with systemic steroids or immunosuppressive agents, are not&#xD;
             candidates for this clinical trial, except for autoimmune hypothyroidism and&#xD;
             well-controlled Type 1 diabetes mellitus.&#xD;
&#xD;
          9. Subjects with or w/o autoimmune condition requiring systemic treatment with either&#xD;
             corticosteroids (&gt;10 mg/day prednisone or equivalent) or other immunosuppressive&#xD;
             medications within 14 days before the planned first dose of study drug. Inhaled or&#xD;
             topical steroids, and adrenal replacement steroid doses &gt; 10 mg daily prednisone&#xD;
             equivalent are permitted in the absence of active autoimmune disease. Ophthalmologic,&#xD;
             nasal and intra-articular injections or steroids are acceptable.&#xD;
&#xD;
         10. Subject with primacy central nervous system (CNS) malignancy or symptomatic CNS&#xD;
             metastases are not allowed. Subjects with asymptomatic CNS metastases are eligible if&#xD;
             clinically controlled, which is defined as ≥8 weeks of stable neurologic function&#xD;
             following CNS-directed therapy, and no evidence of CNS disease progression as&#xD;
             determined by radiographic imaging ≥ 4 weeks prior to screening. No interim&#xD;
             progression between the completion of CNS-directed therapy and the screening tumor&#xD;
             assessment, and ≥ 2 weeks from discontinuation of anti-seizure and steroid therapies&#xD;
             from screening.&#xD;
&#xD;
         11. Subjects who have had major surgery within the 28-days from the screening;&#xD;
&#xD;
         12. Subjects with idiopathic pulmonary fibrosis or unresolved active or chronic&#xD;
             inflammatory pulmonary disease are excluded. Subjects with a history of radiation&#xD;
             pneumonitis which has resolved are eligible.&#xD;
&#xD;
         13. Positive for human immunodeficiency virus (HIV) infection.&#xD;
&#xD;
         14. Active hepatitis B or C. HBV carriers without active disease (HBV DNA titer&lt; 1000&#xD;
             cps/mL or 200 IU/mL), or cured Hepatitis C (negative HCV RNA test) may be enrolled.&#xD;
&#xD;
         15. History of primary immunodeficiency, stem cell or organ transplant, or previous&#xD;
             clinical diagnosis of tuberculosis disease.&#xD;
&#xD;
         16. Subject who have had severe infection deemed clinically significant per investigator&#xD;
             within 4 weeks or signs and symptoms of any active infection within 2 weeks prior to&#xD;
             the first dose administration.&#xD;
&#xD;
         17. Known allergies, hypersensitivity, or intolerance to protein-based therapies or with a&#xD;
             history of any significant drug allergy (e.g., anaphylaxis, hepatotoxicity,&#xD;
             immune-mediated thrombocytopenia or anemia).&#xD;
&#xD;
         18. Subjects who experienced immunotherapy-related adverse events (irAE) grade ≥ 3, or who&#xD;
             had to discontinue prior immunotherapy treatment due to irAEs of any grade.&#xD;
&#xD;
         19. Severe or uncontrolled cardiac disease requiring treatment, congestive heart failure&#xD;
             (New York Heart Association) NYHA III or IV, unstable angina pectoris even if&#xD;
             medically controlled, history of myocardial infarction during the last 6 months,&#xD;
             serious arrhythmias requiring medication (with exception of atrial fibrillation or&#xD;
             paroxysmal supraventricular tachycardia).&#xD;
&#xD;
         20. Any other serious underlying medical (e.g. uncontrolled diabetes mellitus,&#xD;
             uncontrolled hypertension, active gastric ulcer, uncontrolled seizures,&#xD;
             cerebrovascular incidents, gastrointestinal bleeding, severe signs and symptoms of&#xD;
             coagulation and clotting disorders), psychiatric, psychological, familial or&#xD;
             geographical condition that, in the judgment of the investigator, may interfere with&#xD;
             the planned staging, treatment and follow-up, affect subject compliance or place the&#xD;
             subject at high risk from treatment-related complications.&#xD;
&#xD;
         21. Known history of hypersensitivity to any components of the IBI188 product.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>START Midwest</name>
      <address>
        <city>Grand Rapids</city>
        <state>Michigan</state>
        <zip>49546</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Thomas Jefferson Univerity</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19107</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>MD Anderson Cancer Center</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>START (South Texas Accelerated Research Therapeutics, LLC)</name>
      <address>
        <city>San Antonio</city>
        <state>Texas</state>
        <zip>78229</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>November 2021</verification_date>
  <study_first_submitted>November 18, 2018</study_first_submitted>
  <study_first_submitted_qc>December 1, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 4, 2018</study_first_posted>
  <last_update_submitted>December 3, 2021</last_update_submitted>
  <last_update_submitted_qc>December 3, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">December 6, 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>Neoplasms</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <pending_results>
    <submitted>March 18, 2022</submitted>
    <returned>June 30, 2022</returned>
    <submitted>July 6, 2022</submitted>
    <returned>May 5, 2023</returned>
  </pending_results>
  <!-- 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/NCT03763149
org study id: CIBI188A102
nct id: NCT03763149
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
This is an open-label, dose escalation, Phase I study to evaluate the safety, tolerability,
      pharmacokinetics and efficacy in patients with advanced malignancies.
The study is composed of two stages: Part 1 Accelerated Titration Phase and Part 2 Dose
      Escalation Phase with initial fixed priming dose.

      The starting dose for part 1 is 0.1 mg/kg QW, followed by 2 dose cohorts (0.3 mg/kg QW and 1
      mg/kg QW). Duration of dose limiting toxicity (DLT) observation is 28 days.

      Part 2 will have 4 dose cohorts(3mg/kg QW、10mg/kg QW、20mg/kg QW and 30mg/kg QW). Conventional
      3+3 Dose Escalation will be adopted. DLT observation period is 28 days.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Number of patients with AEs and SAEs
time frame: 2 years
description: To evaluate the safety and tolerability of IBI188 [Adverse events (AEs), Serious Adverse Events (SAE) ]
measure: Pharmacokinetics: AUC
time frame: up to 2 years after enrollment
description: The area under the curve (AUC) of serum concentration of the drug after the administration
measure: Pharmacokinetics: Cmax
time frame: up to 2 years after enrollment
description: Maximum concentration(Cmax) of the drug after administration
measure: Immunogenicity: Percentage of ADA positive patients
time frame: up to 2 years after enrollment
description: Number of Anti-Drug Antibodies (ADA) positive patients will be counted and percentage of ADA positive patients will be calculated to evaluate immunogenicity of IBI188.
measure: Preliminary anti-tumor activity of IBI188 (Objective Response Rate)
time frame: up to 2 years after enrollment
description: Objective Response Rate (ORR) is the percentage of Complete Response (CR) plus partial response (PR) assessed by iRECIST v1.1 criteria for solid tumors and Lugano2014 criteria for lymphoma.
arm group label: IBI188
arm group type: Experimental
description: Part 1: Accelerated Titration Phase 0.1 mg/kg IV; QW 0.3 mg/kg IV QW; 1 mg/kg IV QW
Part 2 : Dose Escalation Phase with initial fixed priming dose Priming dose of 1mg/kg on C1D1 followed by 3 mg/kg IV QW; 10 mg/kg IV QW; 20 mg/kg IV QW; 30 mg/kg IV QW.
intervention type: Biological
intervention name: IBI188
description: The study is composed of two stages: Part 1 Accelerated Titration Phase and Part 2 Dose Escalation Phase with initial fixed priming dose.
The starting dose for part 1 is 0.1 mg/kg QW, followed by 2 dose cohorts (0.3 mg/kg QW and 1 mg/kg QW). Duration of dose limiting toxicity (DLT) observation is 28 days.
Part 2 will have 4 dose cohorts(3mg/kg QW、10mg/kg QW、20mg/kg QW and 30mg/kg QW). Conventional 3+3 Dose Escalation will be adopted. DLT observation period is 28 days.
arm group label: IBI188
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Neoplasms
sharing ipd: No
submitted: March 18, 2022
returned: June 30, 2022
submitted: July 6, 2022
returned: May 5, 2023