IBI188 Combination Therapy in Solid Tumors

Study Overview
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Brief Summary
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A Phase Ib study aim to evaluate the efficacy, safety, and tolerability of IBI188 combination therapy in subjects with advanced malignancies

Official Title
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Phase Ib Study to Evaluate the Efficacy, Safety and Tolerability of IBI188 Combination Therapy in Subjects With Advanced Malignancies

Conditions
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Solid Tumors, Lung Adenocarcinoma, Osteosarcoma

Intervention / Treatment
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* Drug: IBI188
* Drug: GM-CSF
* Drug: Cisplatin/Carboplatin
* Drug: Bevacizumab
* Drug: Sintilimab
* Drug: Pemetrexed


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with locally advanced or metastatic solid tumors cannot be cured by surgery or other local treatments . Aged ≥ 18 years (≥ 12 years is acceptable in Cohort C). Able to provide archived or fresh tumor tissue samples for biomarker assessment. Have at least one measurable lesion according to RECIST version 1.1. ECCG PS score of 0-2. Adequate organ and bone marrow functions . Life expectancy ≥ 12 weeks. Female subjects of childbearing potential or male subjects with partners of childbearing potential should take effective contraceptive measures throughout the whole treatment period and until 6 months after treatment. Must voluntarily sign the Informed Consent Form (ICF), and be able to follow all study requirements and procedures. For the subjects enrolled in Cohort C who are ≥ 12 and < 18 years old, in addition to obtaining the child's own consent, their guardians should provide informed consent and sign the ICF. Exclusion Criteria: Previous exposure to any CD47 antibody, SIRPα antibody, CD47/SIRPα recombinant protein or other inhibitors that act in the same pathway. Previous exposure to any anti-programmed death receptor 1 (PD-1) or anti-programmed death-ligand (PD-L1) antibody (except Cohort C). Concurrent participation in another clinical study. The last dose of anti-tumor therapy is within 4 weeks before the first dose of study treatment. Have undergone major surgical procedures within 4 weeks prior to the first dose of study treatment or planned to receive major surgery during the study treatment. Presence of toxicities (excluding alopecia and fatigue) induced by previous anti-tumor therapy that has not recovered to Grade 0 or 1 as assessed by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5.0 prior to the first dose of study treatment. Known hypersensitivity to IBI188 or any ingredient in the study drug product. History of other primary malignancies. Female subjects who are pregnant or lactating. Other ineligible conditions considered by the investigator.

Ages Eligible for Study
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Minimum Age: 12 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort A<br> | Drug: IBI188<br>* intravenous<br>Drug: Sintilimab<br>* intravenous<br>|
| Experimental: Cohort B<br> | Drug: IBI188<br>* intravenous<br>Drug: Cisplatin/Carboplatin<br>* intravenous<br>Drug: Bevacizumab<br>* intravenous<br>Drug: Pemetrexed<br>* intravenous<br>|
| Experimental: Cohort C<br> | Drug: IBI188<br>* intravenous<br>Drug: GM-CSF<br>* subcutaneous injection<br>|
| Experimental: Cohort D<br> | Drug: IBI188<br>* intravenous<br>Drug: Sintilimab<br>* intravenous<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate |  | 24 months | 
| Adverse Events | 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) | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival |  | 24 months | 
| Overall survival |  | 24 months | 
| Disease control rate |  | 24 months | 
| Duration of response |  | 24 months | 
| Time to response |  | 24 months | 
| Area Under Curve, AUC |  | 24 months | 
| maximum concentration (Cmax) |  | 24 months | 
| minimum concentration (Cmin) |  | 24 months | 
| clearance (CL) |  | 24 months | 
| volume of distribution (V) |  | 24 months | 
| half-life (t1/2) |  | 24 months | 
| Positive rate of anti-drug antibody (ADA) |  | 24 months | 
| Positive rate of neutralizing antibody (NAb) |  | 24 months |