Clinical Trials /

IBI308 in Subjects With Advanced/Metastatic Solid Malignancies

NCT03568539

Description:

The study is to evaluate preliminary anti-tumor activity (overall response rate, ORR) of IBI308 monotherapy in subjects with advanced/metastatic solid malignancies. Patients will be recruited for 2 cohorts: Cohort 1: Approximately 60 subjects with advanced/metastatic cancer and high tumor mutational burden (TMB); Cohort 2: 20 subjects with advanced/metastatic endometrial cancer (EC).

Related Conditions:
  • Endometrial Carcinoma
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: IBI308 in Subjects With Advanced/Metastatic Solid Malignancies
  • Official Title: An Open-label, Phase 1b Multicenter Study of IBI308 in Subjects With Advanced/Metastatic Solid Malignancies

Clinical Trial IDs

  • ORG STUDY ID: CIBI308A102
  • NCT ID: NCT03568539

Conditions

  • Advanced/Metastatic Solid Malignancies

Interventions

DrugSynonymsArms
IBI308IBI308

Purpose

The study is to evaluate preliminary anti-tumor activity (overall response rate, ORR) of IBI308 monotherapy in subjects with advanced/metastatic solid malignancies. Patients will be recruited for 2 cohorts: Cohort 1: Approximately 60 subjects with advanced/metastatic cancer and high tumor mutational burden (TMB); Cohort 2: 20 subjects with advanced/metastatic endometrial cancer (EC).

Trial Arms

NameTypeDescriptionInterventions
IBI308Experimental

    Eligibility Criteria

            Inclusion Criteria:
    
              1. Subjects able to give voluntary informed consent, understand the study and are willing
                 to follow and complete all the test procedures.
    
              2. Subjects (males and females) of childbearing potential should be willing to use
                 reliable contraception methods that are deemed effective by the investigator 1 month
                 prior to treatment and throughout the treatment period and for 90 days following the
                 last dose of study drug. Postmenopausal women must have been amenorrheal for at least
                 12 months to be considered of non-childbearing potential.
    
              3. Male or female subjects >18 years
    
                   1. At least one measurable lesion (per RECIST version 1.1)
    
                   2. Eastern Cooperative Oncology Group (ECOG) Performance Status ≤1.
    
                   3. Subjects with life expectancy of ≥ 3 month
    
              4. If subject received anti-tumor therapy:
    
                   1. Generalized radiation therapy must have been completed 3 weeks prior to
                      enrollment, or local radiotherapy or radiation therapy for bone metastases for 2
                      weeks prior to enrollment. Treatment with radiopharmaceuticals must have been
                      completed 8 weeks prior to enrollment.
    
                   2. Previous chemotherapy, biotherapy (tumor vaccines, cytokines, or growth factors
                      that control cancer), tyrosine kinase inhibitors, or approved targeting and other
                      treatments should have completed at least 3 weeks prior to the first administered
                      dose in this study;
    
              5. Subjects must have adequate organ function (liver, kidney function and hematopoietic
                 function tests) prior IBI308 administration
    
                   1. Absolute neutrophil count (ANC) ≥1.5 x109/L
    
                   2. Platelet count ≥ 100 x 109/L
    
                   3. Hemoglobin ≥ 9 g / dL (whole blood or component transfusion within 7 days before
                      1st dose of study drug is prohibited)
    
                   4. Renal function tests: serum creatinine ≤1.5 ×upper limit of normal range (ULN) or
                      an estimated glomerular filtration rate (eGFR) ≥ 50 mL/min/1.73 m2
    
                   5. Liver function tests alanine aminotransferase (ALT) and aspartate
                      aminotransferase (AST) ≤3 x ULN, for patients with known liver cancer or liver
                      metastases, AST and ALT ≤ 5 x ULN
    
                   6. Total bilirubin (TBil) ≤1.5 x ULN; If Gilbert's Syndrome may have Bilirubin> 1.5
                      x ULN
    
                   7. Coagulation tests: aPTT ≤ 1.5 x ULN and INR ≤2.0
    
              6. Cohort Specific Inclusion Criteria:
    
            Cohort 1: Advanced/metastatic cancers with high TMB expression
    
              1. Cohort 1a: Advanced/metastatic cancers with TMB level for 10 to less than 15mut/Mb
    
              2. Cohort 1b: Advanced/metastatic cancers with TMB level between 15~20mut/Mb
    
              3. Cohort 1c: Advanced/metastatic cancers with TMB level >20 mut/Mb
    
            Other Specific Inclusion Criteria for cohort 1:
    
            i. Histologically or cytologically confirmed unresectable Stage III/IV NSCLC or other
            advanced/metastatic cancers (for example, melanoma, bladder cancer, SCLC, prostate cancer,
            colorectal cancer, gastric cancer) ii. Separate informed consent is required for subjects
            who provide fresh biopsies for serial tumor biopsies for biomarker testing. TMB testing
            should be performed on the most recently obtained tumor sample.
    
            iii. Subjects must be tested for TMB level before entering the study, and pre-screen
            informed consent is required for TMB testing. Subjects who have existing FoundationOne TMB
            testing results from within 6 months of study entry do not need to have repeat testing.
    
            iv. Refractory or intolerant to standard therapy or for whom no standard therapy exists.
            Subjects must have no available therapy likely to confer clinical benefit for their cancer.
            Subjects who experienced irAE grade ≥ 3, or grade 2 recurrent pneumonitis, or who had to
            discontinue prior anti-PD-1/PD-L1 treatment due to irAEs of any grade will not be eligible.
    
            v. NSCLC subjects with EGFR mutation and/or ALK rearrangement and/or ROS-1 positive, should
            have received appropriate targeted therapy and are refractory to targeted therapy prior to
            enrolling this trial.
    
            Cohort 2: Advanced/metastatic endometrial Cancer i. Histologically confirmed
            advanced/metastatic endometrial cancer. ii. Refractory or intolerant to standard therapy,
            and no available therapy likely to confer clinical benefit for their cancer. Subjects who
            experienced irAE grade ≥ 3, or who had to discontinue prior anti-PD-1/PD-L1 treatment due
            to irAEs of any grade will not be eligible.
    
            Exclusion Criteria:
    
              1. Legal incapacity or limited legal capacity.
    
              2. Pregnancy, lactation, breastfeeding.
    
              3. Concurrent anticancer treatment (e.g., cytoreductive therapy or cytokine therapy
                 except for erythropoietin) or use of other investigational product within 28 days
                 before start of trial treatment; major surgery within 28 days before start of trial
                 treatment (excluding prior diagnostic biopsy.
    
              4. Note: Small molecule or antibody targeted therapy < 3 weeks from start of trial
                 treatment will be excluded.
    
              5. Received a biologic (G-CSF, GM-CSF) within 14 days prior to the first dose of study
                 drug.
    
              6. Vaccination within 4 weeks of first dose of IBI308 and while on study except for
                 administration of inactivated vaccines (e.g., inactivated influenza vaccines)
    
              7. Failure to recover from adverse events from the most recent anti-tumor treatment to
                 CTCAE ≤ grade 1 or baseline with the exception of alopecia;
    
              8. Active autoimmune disease requiring systemic treatment within the past 1 year or a
                 documented history of clinically severe autoimmune disease or a syndrome that requires
                 systemic steroids or immunosuppressive agents during the conduct of this study.
                 Exceptions: - Vitiligo, eczema, psoriasis (<10% of body surface area (BSA) of skin
                 eruption or systemic involvement) or resolved childhood asthma/atopy, autoimmune
                 hypothyroidism stable on hormone replacement.
    
              9. History of idiopathic pulmonary fibrosis, pneumonitis (including drug induced),
                 organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing
                 pneumonia, etc.), or evidence of active pneumonitis on screening chest computed
                 tomography (CT) scan. History of radiation pneumonitis in the radiation field
                 (fibrosis) is permitted.
    
             10. Acute or chronic hepatitis B, hepatitis C or human immunodeficiency virus (HIV)
                 infection.
    
             11. History of primary immunodeficiency, stem cell or organ transplant, or previous
                 clinical diagnosis of tuberculosis.
    
             12. Subject who have had severe infection within 4 weeks or signs and symptoms of any
                 active infection within 2 weeks prior to the first dose administration.
    
             13. Known allergies, hypersensitivity, or intolerance to protein-based therapies or with a
                 history of any significant drug allergy (e.g., anaphylaxis, hepatotoxicity,
                 immune-mediated thrombocytopenia or anemia
    
             14. Subjects who experienced (irAE) grade≥3 immunotherapy-related adverse events. Subjects
                 with CNS metastasis unless they are asymptomatic or adequately treated with
                 radiotherapy and/or surgery and subjects are neurologically stable with minimal
                 residual symptoms/signs 14 days prior to dosing.
    
             15. Patients who require high dose of systemic corticosteroids (>10 mg/day prednisone or
                 equivalents) for at least 2 weeks prior to treatment are not eligible.
    
             16. Severe or uncontrolled cardiac disease requiring treatment, congestive heart failure
                 (New York Heart Association) NYHA III or IV, unstable angina pectoris even if
                 medically controlled, history of myocardial infarction during the last 3 months,
                 serious arrhythmias requiring medication (with exception of atrial fibrillation or
                 paroxysmal supraventricular tachycardia).
    
             17. Any other serious underlying medical (e.g., uncontrolled hypertension, active
                 uncontrolled infection, active gastric ulcer, uncontrolled seizures, cerebrovascular
                 incidents, gastrointestinal bleeding, severe signs and symptoms of coagulation and
                 clotting disorders, other serious cardiac conditions not listed in exclusion
                 criteria), psychiatric, psychological, familial or geographical condition that, in the
                 judgment of the investigator, may interfere with the planned staging, treatment and
                 follow-up, affect patient compliance or place the patient at high risk from
                 treatment-related complications.
          
    Maximum Eligible Age:N/A
    Minimum Eligible Age:18 Years
    Eligible Gender:All
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Overall Response Rate
    Time Frame:2 years
    Safety Issue:
    Description:To evaluate preliminary anti-tumor activity (overall response rate, ORR) of IBI308 monotherapy in subjects with advanced/metastatic solid malignancies. ORR includes CR and PR assessed by iRECIST v1.1 criteria.

    Secondary Outcome Measures

    Measure:Progression-free survival
    Time Frame:2 years
    Safety Issue:
    Description:To measure progression-free survival rate (PFS)
    Measure:Duration of response
    Time Frame:2 years
    Safety Issue:
    Description:To measure duration of response (DOR)
    Measure:Overall survival
    Time Frame:2 years
    Safety Issue:
    Description:To measure overall survival rate (OS)
    Measure:Immunogenicity
    Time Frame:Up to 2 years.
    Safety Issue:
    Description:Anti-Drug Antibodies will be tested to evaluate immunogenicity of IBI308
    Measure:Maximum Plasma Concentration [Cmax]
    Time Frame:Till 30 days after the last dose of IP. Up to 2 years.
    Safety Issue:
    Description:To evaluate the Maximum Plasma Concentration [Cmax] of IBI308.
    Measure:Area Under the Curve [AUC]
    Time Frame:Till 30 days after the last dose of IP. Up to 2 years.
    Safety Issue:
    Description:To evaluate the Area Under the Curve [AUC] of IBI308.

    Details

    Phase:Phase 1/Phase 2
    Primary Purpose:Interventional
    Overall Status:Not yet recruiting
    Lead Sponsor:Innovent Biologics (Suzhou) Co. Ltd.

    Trial Keywords

    • Advanced/metastatic solid malignancies, TMB high

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