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.
Inclusion Criteria:
1. Able to understand and willing to sign the ICF.
2. Male or female subject above18 years.
3. Histologically/cytologically confirmed, locally advanced unresectable or metastatic
solid tumors and lymphomas that are refractory to standard therapy, or for which no
standard therapy exists.
4. For dose expansion at the RP2D: subject has measurable disease per RECIST v1.1. that
was not in a prior radiation area within past 6 months, unless tumor growth was
documented following radiation. Lymphomas have at least one measurable lesion and
FDG-avid lesion according to the Lugano 2014 criteria.
5. Separate informed consent for subjects who provide archived tissue biopsies for
biomarker testing (Optional).
6. ECOG Performance Status 0 to 1
7. Subjects with life expectancy of ≥ 3 month
8. No herbal/alternative medications within 14 days prior to the first dose of IBI188.
9. Must have adequate organ function, prior to start of IBI188, including the following:
1. Bone marrow reserve: absolute neutrophil count (ANC) ≥ 1.5 x109/L; platelet count
≥ 100 x 109/L; hemoglobin ≥ 9 g/dL or ≥ 5.6 mmol/L; Lymphocyte counts ≥ 0.5
x109/L
2. Hepatic: total bilirubin ≤ 1.5 times the upper limit of normal (ULN), aspartate
transaminase (AST) and/or alanine aminotransferase (ALT) ≤ 2.5 X ULN (≤5 X ULN if
with liver involvement)
3. Renal: serum creatinine ≤ 1.5 times the ULN or estimated creatinine clearance
≥50mL/min (Cockroft and Gault formula
[https://www.mdcalc.com/creatinine-clearance-cockcroft-gault-equation]).
4. Coagulation tests INR < 2.0, activated partial thromboplastin time (aPTT) ≤ 1.5 x
ULN
10. Subjects (women of child-bearing potential and males) must be willing to use viable
contraception method that is deemed effective by the investigator throughout the
treatment period and for at least three months following the last dose of study drug.
Postmenopausal women must have been amenorrhoeic for at least 12 months to be
considered of non-childbearing potential.
Exclusion Criteria:
1. Pregnant or nursing females.
2. Any remaining AEs > grade 1 from prior anti-tumor treatment as per CTCAE v5.0, with
exception of the residual hair loss;
3. Received a biologic G-CSF, GM-CSF or erythropoietin within 14 days prior to the first
dose of study drug;
4. Subjects participating in any other interventional clinical study
5. Previous exposure to any anti-CD47 monoclonal antibody or SIRPα antibody.
6. Subjects who had transfusion within 3 weeks
7. Patients who are on anticoagulants and /or require concomitant aspirin or other
nonsteroidal anti-inflammatory medications.
8. Subjects who have a history of documented autoimmune disease, even if not clinically
severe or never treated with systemic steroids or immunosuppressive agents, are not
candidates for this clinical trial, except for autoimmune hypothyroidism and
well-controlled Type 1 diabetes mellitus.
9. Subjects with or w/o autoimmune condition requiring systemic treatment with either
corticosteroids (>10 mg/day prednisone or equivalent) or other immunosuppressive
medications within 14 days before the planned first dose of study drug. Inhaled or
topical steroids, and adrenal replacement steroid doses > 10 mg daily prednisone
equivalent are permitted in the absence of active autoimmune disease. Ophthalmologic,
nasal and intra-articular injections or steroids are acceptable.
10. Subject with primacy central nervous system (CNS) malignancy or symptomatic CNS
metastases are not allowed. Subjects with asymptomatic CNS metastases are eligible if
clinically controlled, which is defined as ≥8 weeks of stable neurologic function
following CNS-directed therapy, and no evidence of CNS disease progression as
determined by radiographic imaging ≥ 4 weeks prior to screening. No interim
progression between the completion of CNS-directed therapy and the screening tumor
assessment, and ≥ 2 weeks from discontinuation of anti-seizure and steroid therapies
from screening.
11. Subjects who have had major surgery within the 28-days from the screening;
12. Subjects with idiopathic pulmonary fibrosis or unresolved active or chronic
inflammatory pulmonary disease are excluded. Subjects with a history of radiation
pneumonitis which has resolved are eligible.
13. Positive for human immunodeficiency virus (HIV) infection.
14. Active hepatitis B or C. HBV carriers without active disease (HBV DNA titer< 1000
cps/mL or 200 IU/mL), or cured Hepatitis C (negative HCV RNA test) may be enrolled.
15. History of primary immunodeficiency, stem cell or organ transplant, or previous
clinical diagnosis of tuberculosis disease.
16. Subject who have had severe infection deemed clinically significant per investigator
within 4 weeks or signs and symptoms of any active infection within 2 weeks prior to
the first dose administration.
17. 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).
18. Subjects who experienced immunotherapy-related adverse events (irAE) grade ≥ 3, or who
had to discontinue prior immunotherapy treatment due to irAEs of any grade.
19. 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 6 months,
serious arrhythmias requiring medication (with exception of atrial fibrillation or
paroxysmal supraventricular tachycardia).
20. Any other serious underlying medical (e.g. uncontrolled diabetes mellitus,
uncontrolled hypertension, active gastric ulcer, uncontrolled seizures,
cerebrovascular incidents, gastrointestinal bleeding, severe signs and symptoms of
coagulation and clotting disorders), psychiatric, psychological, familial or
geographical condition that, in the judgment of the investigator, may interfere with
the planned staging, treatment and follow-up, affect subject compliance or place the
subject at high risk from treatment-related complications.
21. Known history of hypersensitivity to any components of the IBI188 product.
