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).
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
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.
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
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)
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