NCT03717103CompletedPhase 1
A Phase 1 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 Malignancies
Innovent Biologics (Suzhou) Co. Ltd.1 site in 1 country49 target enrollmentStarted: January 10, 2019Last updated:
Conditions
Interventions
Drugs
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Enrollment
- 49
- Locations
- 1
- Primary Endpoint
- Adverse events (AEs), Serious Adverse Events (SAE)Number of patients with AEs and SAEs
Study Overview
Brief Summary
This is an open-label, dose escalation, Phase I study to evaluate the safety, tolerability, pharmacokinetics and efficacy in patients with advanced malignancies.
Detailed Description
Phase Ia study is composed of two stages: Phase Ia Part A initial dose escalation and Phase Ia Part B maintenance dose escalation. Both parts will adopt the classical 3+3 dose escalation design. The starting dose for phase Ia part A 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 14 days.
Phase Ia Part B will have 4 dose cohorts(3mg/kg QW#10mg/kg QW#20mg/kg QW #30mg/kg QW and 45mg/kg Q3W). DLT observation period is 28 days. The subject number for each cohort in Phase Ia Part B will be increased to 6 if the subject number enrolled in each cohort is less than 6
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Advanced solid tumors and lymphomas defined by:
- •Histologically/cytologically confirmed solid tumors and lymphomas
- •Solid Tumors failed from standard therapy
- •Lymphoma patients who have had at least two standard treatment failures
- •Subject has at least 1 measurable disease per RECIST v1.
- •Lymphomas have at least one measurable lesion and 18FDG-avid lesion according to the Lugano 2014 criteria.
- •Male or female subject above 18 years
- •ECOG Performance Status 0 to 1
- •Must have adequate organ and bone marrow function, including the following:
- •Blood routine: absolute neutrophil count (ANC) ≥ 1.5 x10^9/L; platelet count ≥ 75 x 10^9/L; hemoglobin ≥ 10 g/dL. (For subjects with AML, WBC < 25×10^9/L was required , and there is no restriction for the rest in blood routine test ).
- •Hepatic: total bilirubin ≤ 1.5 times of 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). total bilirubin ≤ 3×ULN if subjects were diagnosed with Gilbert syndrome.
- •Renal: serum creatinine ≤ 1.5 X ULN or estimated creatinine clearance ≥50mL/min. Urinary protein < 2+. For subjects with urinary protein ≥2+ at baseline, a 24h urine collection should be performed with urine protein < 1g.
- •Coagulation tests INR < 1.5, partial prothrombin time (PT) or activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN
- •Subjects with life expectancy of ≥ 12 weeks
- •Female subjects of child-bearing potential or male subjects with female partners of child-bearing potential must be willing to use viable contraception method that is deemed effective by the investigator throughout the treatment period and for at least 6 months following the last dose of study drug.
- •Be willing to sign the Informed Consent Form (ICF), and can follow the visit schedule and procedures defined in the protocol.
Exclusion Criteria
- •Previous exposure to any anti-CD47 monoclonal antibody or SIRPα antibody.
- •Subjects participating in any other interventional clinical study
- •Received blood transfusion, biologic G-CSF, GM-CSF, erythropoietin, thrombopoietin (TPO) or IL-11within 3 weeks prior to the first dose of study drug
- •Receive the last dose of anti-tumor therapy (chemotherapy, endocrine therapy, targeted therapy, immunotherapy or tumor embolization, etc.) within 3 weeks before the first dose of the study.
- •Immunosuppressive drugs were used within 7 days before the first dose of the study
- •Plan to receive live attenuated vaccines within 4 weeks before the first dose treatment or during the study period.
- •Has undergone major surgery (craniotomy, thoracotomy or laparotomy) or is expected to require major surgery during the first dose of the study.
- •Any remaining AEs > grade 1 from prior anti-tumor treatment as per CTCAE v5.0, with exception of the residual hair loss nor fatigue
- •Had received total pelvic radiotherapy before.
- •Central nervous system metastases:
- •Subjects with active or suspected autoimmune disease or a history of the disease in the past two years
- •known history of primary immunodeficiency.
- •known history of active pulmonary tuberculosis.
- •known history of allograft transplantation and history of allogeneic hematopoietic stem cell transplantation.
- •known to be allergic to any IBI188 preparations.
- •Ascites of clinical significance, including any ascites that may be detected by physical examination, previously treated or still in need of treatment, may be enrolled if only a small amount of ascites is shown on imaging but asymptomatic.
- •Subjects with moderate bilateral pleural effusion, or massive pleural effusion on one side, or respiratory dysfunction requiring drainage.
- •Pregnant or nursing females.
Arms & Interventions
IBI188
Experimental
Part A : Initial dose escalation, Part B : Maintenance dose escalation
Intervention: IBI188 (Drug)
Outcomes
Primary Outcomes
Adverse events (AEs), Serious Adverse Events (SAE)Number of patients with AEs and SAEs
Time Frame: 24 months
Incidence, correlation with the study drug and severity of all adverse events (AEs), treatment-emergent adverse events (TEAEs), adverse events of special interest (AESIs) and serious adverse events (SAEs).
Secondary Outcomes
- Preliminary anti-tumor activity of IBI188 (Objective Response Rate)(24 months)
- Pharmacokinetics: AUC(24 months)
- Pharmacokinetics: Cmax(24 months)
- Immunogenicity(24 months)
Investigators
Study Sites (1)
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