A Phase 1 Study Evaluating the Safety, Tolerability, and Initial Efficacy of IBI188 in Advanced Malignancies
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
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
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: IBI188 Part A : Initial dose escalation, Part B : Maintenance dose escalation |
Drug: IBI188
Part A: 0.1 mg/kg IV QW, 0.3 mg/kg IV QW, 1 mg/kg IV QW. Part B: 1mg/kg IV D1+3, 10, 20, 30 mg/kg IV D8 QW or 45mg/kg D8 IV Q3W.
Other Names:
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Outcome Measures
Primary Outcome Measures
- Adverse events (AEs), Serious Adverse Events (SAE)Number of patients with AEs and SAEs [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 Outcome Measures
- Preliminary anti-tumor activity of IBI188 (Objective Response Rate) [24 months]
Objective Response Rate (ORR) is the percentage of Complete Response (CR) plus partial response (PR) assessed by RECIST v1.1 criteria for solid tumors and Lugano2014 criteria for lymphoma.
- Pharmacokinetics: Cmax [24 months]
Maximum concentration(Cmax) of the drug after administration
- Pharmacokinetics: AUC [24 months]
The area under the curve (AUC) of serum concentration of the drug after the administration.
- Immunogenicity [24 months]
Anti-Drug Antibodies (ADA) will be tested and percentage of ADA positive patients will be calculated to evaluate immunogenicity of IBI188.
Eligibility Criteria
Criteria
Inclusion Criteria:
- Advanced solid tumors and lymphomas defined by:
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Histologically/cytologically confirmed solid tumors and lymphomas
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Solid Tumors failed from standard therapy
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Lymphoma patients who have had at least two standard treatment failures
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Subject has at least 1 measurable disease per RECIST v1.1. Lymphomas have at least one measurable lesion and 18FDG-avid lesion according to the Lugano 2014 criteria.
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Male or female subject above 18 years
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ECOG Performance Status 0 to 1
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Must have adequate organ and bone marrow function, including the following:
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Blood routine: absolute neutrophil count (ANC) ≥ 1.5 x109/L; platelet count ≥ 75 x 109/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 ).
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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.
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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.
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Coagulation tests INR < 1.5, partial prothrombin time (PT) or activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN
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Subjects with life expectancy of ≥ 12 weeks
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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.
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Be willing to sign the Informed Consent Form (ICF), and can follow the visit schedule and procedures defined in the protocol.
Exclusion Criteria:
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Previous exposure to any anti-CD47 monoclonal antibody or SIRPα antibody.
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Subjects participating in any other interventional clinical study
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Received blood transfusion, biologic G-CSF, GM-CSF, erythropoietin, thrombopoietin (TPO) or IL-11within 3 weeks prior to the first dose of study drug
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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.
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Immunosuppressive drugs were used within 7 days before the first dose of the study
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Plan to receive live attenuated vaccines within 4 weeks before the first dose treatment or during the study period.
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Has undergone major surgery (craniotomy, thoracotomy or laparotomy) or is expected to require major surgery during the first dose of the study.
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Any remaining AEs > grade 1 from prior anti-tumor treatment as per CTCAE v5.0, with exception of the residual hair loss nor fatigue
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Had received total pelvic radiotherapy before.
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Central nervous system metastases:
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Subjects with active or suspected autoimmune disease or a history of the disease in the past two years
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known history of primary immunodeficiency.
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known history of active pulmonary tuberculosis.
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known history of allograft transplantation and history of allogeneic hematopoietic stem cell transplantation.
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known to be allergic to any IBI188 preparations.
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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.
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Subjects with moderate bilateral pleural effusion, or massive pleural effusion on one side, or respiratory dysfunction requiring drainage.
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Pregnant or nursing females.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Beijing Cancer Hospital | Beijing | Beijing | China | 100142 |
Sponsors and Collaborators
- Innovent Biologics (Suzhou) Co. Ltd.
Investigators
- Principal Investigator: Song Yuqin, Peking University Cancer Hospital & Institute
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- CIBI188A101