A Study Evaluating the Safety, Tolerability, and Initial Efficacy of Recombinant Human Anti-T-cell Immunoreceptor With Ig and ITIM Domains (TIGIT) Monoclonal Antibody Injection (IBI939) in Subjects With Advanced Malignant Tumors
Study Details
Study Description
Brief Summary
This is an open-label, dose escalation, Phase I study to evaluate the safety, tolerability, pharmacokinetics and efficacy of IBI939 in subjects with advanced malignancies
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
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Phase 1 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Phase Ia Dose-Escalation Stage:IBI939 Participants will be treated with escalating doses of IBI939 to determine the MTD. |
Drug: IBI939
Several dose levels will be evaluated for IBI939 administered as a single agent and in combination with Sintilimab. IBI939 will be given via intravenous (IV) infusion on Day 1 of each 21-day cycle until disease progression or loss of clinical benefit. Those who discontinue treatment with single-agent IBI939 may receive combination treatment with Sintilimab or IBI939+ Sintilimab. Combination treatment may continue until disease progression or loss of clinical benefit.
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| Experimental: Phase Ia Dose-Escalation Stage:IBI939+ Sintilimab Participants will be treated with escalating doses of IBI939 in combination with a fixed dose of Sintilimab to determine the MTD. |
Drug: IBI939+ Sintilimab
IBI939: Several dose levels will be evaluated for IBI939 in combination with Sintilimab. IBI939 will be given via intravenous (IV) infusion on Day 1 of each 21-day cycle until disease progression or loss of clinical benefit.
Sintilimab: Sintilimab will be given as 200 mg via IV infusion on Day 1 of each 21-day cycle in combination with IBI939. Combination treatment may continue until disease progression or loss of clinical benefit.
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| Experimental: Phase Ib Expansion Stage:IBI939+ Sintilimab Participants will be enrolled in the expansion stage to better characterize the safety, tolerability, PK variability, and preliminary efficacy of IBI939 in combination with Sintilimab in different cancer types. |
Drug: IBI939+ Sintilimab
IBI939: IBI939 in combination with Sintilimab will be given with RP2D. IBI939 will be given via intravenous (IV) infusion on Day 1 of each 21-day cycle until disease progression or loss of clinical benefit.
Sintilimab: Sintilimab will be given as 200 mg via IV infusion on Day 1 of each 21-day cycle in combination with IBI939. Combination treatment may continue until disease progression or loss of clinical benefit.
|
Outcome Measures
Primary Outcome Measures
- Number of subjects with AEs and SAEs [up to 2 years after enrollment]
To evaluate the safety and tolerability of IBI939 alone or in combination with Sintilimab [Adverse events (AEs), Serious Adverse Events (SAEs) ]
- Percentage of Participants with Dose-Limiting Toxicities (DLTs) [From Baseline to the end of Cycle 1]
To evaluate the safety and tolerability of IBI939 alone or in combination with Sintilimab.
Secondary Outcome Measures
- Pharmacokinetics: AUC [up to 2 years after enrollment]
The area under the curve (AUC) of serum concentration of the drug after the administration.
- Pharmacokinetics: Cmax [up to 2 years after enrollment]
Maximum concentration (Cmax) of the drug after administration
- Immunogenicity: Percentage of ADA positive subjects [up to 2 years after enrollment]
Immunogenicity: Number of Anti-Drug Antibodies (ADA) positive subjects will be counted and percentage of ADA positive subjects will be calculated to evaluate immunogenicity of IBI939.
- Preliminary anti-tumor activity (Objective Response Rate) [up to 2 years after enrollment]
Objective Response Rate (ORR) is the percentage of Complete Response (CR) plus partial response (PR) assessed by RECIST v1.1 criteria for solid tumors.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Able to understand and willing to sign the ICF.
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Adults 18 years of age or older.
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Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
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Life expectancy at least 12 weeks.
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Adequate organ and bone marrow function.
Eligibility Criteria：
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Previous exposure to any anti-TIGIT antibody.
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Participate in another interventional clinical study, except for the observational (non-interventional) clinical study or the survival follow-up phase of the interventional study.
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Any investigational drugs received within 4 weeks prior to the first study treatment.
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Receive the last dose of anti-tumor therapy within 4 weeks before the first dose of study therapy.
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Immunosuppressive drugs were used within 4 weeks prior to the first administration of the study drug.
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Medication requiring long-term systemic hormones or any other immunosuppression therapy.
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Major surgical procedures (craniotomy, thoracotomy, or laparotomy) or unhealed wounds, ulcers, or fractures were performed within 4 weeks prior to the first dose of study therapy.
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Primary central nervous system (CNS) malignancy, or untreated/active CNS metastases, or leptomeningeal disease.
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History of autoimmune disease , present active autoimmune disease or inflammatory diseases
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Positive human immunodeficiency virus (HIV) test.
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Active hepatitis B or C, or tuberculosis.
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History of allogeneic organ transplantation and allogeneic hematopoietic stem cell transplantation.
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Known history of hypersensitivity to any components of the IBI939 or Sintilimab.
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Pregnant or nursing females.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Peking University Cancer Hospital & Institute | Beijing | China |
Sponsors and Collaborators
- Innovent Biologics (Suzhou) Co. Ltd.
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- CIBI939A101