Study of IBI318 in Participants With Advanced Malignancies

Study Overview
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Brief Summary
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An open label, multicenter, phase Ia/Ib study to evaluate the safety, tolerability, and initial efficacy of IBI318 in the treatment of patients with advanced malignancies.

Detailed Description
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An open label, multicenter, phase Ia/Ib study to evaluate the safety, tolerability, and initial efficacy of IBI318 in the treatment of patients with advanced malignancies.

Official Title
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To Evaluate the Safety, Tolerability, and Initial Efficacy of IBI318 in Patients With Advanced Malignancy, Multicenter, IA/IB Study

Conditions
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Advanced Malignancy

Intervention / Treatment
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* Biological: IBI318
* Biological: IBI318
* Biological: IBI318
* Biological: IBI318
* Biological: IBI318
* Biological: IBI318
* Biological: IBI318
* Biological: IBI318
* Biological: IBI318
* Biological: IBI318
* Biological: IBI318


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Sign the informed consent form Men or women 18 years or older Expected survival time ≥ 12 weeks Tumor assessment according to RECIST v1.1, at least one measurable lesion Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 Have adequate organ and bone marrow function Male participants and female participants must agree to use contraception during the treatment period and within 180 days after the treatment period Female subjects must not be pregnant or breastfeeding. If premenopausal, negative urine or serum pregnancy tests are required Ia: Subjects with locally advanced, recurrent or metastatic histologically or cytologically confirmed solid tumors or hematologic tumors and are refractory or intolerant to existing standard treatments Ib: Metastatic non-small cell lung cancer, advanced liver cancer, advanced esophageal squamous cell cancer, advanced gastric cancer, or other tumors that have been proved by histology or cytology with initial therapeutic effect in Phase Ia Exclusion Criteria: Previous exposure to immunotherapy including but not limited to, anti-CTLA-4, anti-PD-1, anti-PD-L1, and anti-PD-L2 antibodies, excluding therapeutic anti-tumor vaccine Participation in another interventional clinical study, an observational (non-interventional) clinical study, or a follow-up phase of an interventional study Receive last anti-tumor treatment within 4 weeks prior to the first dose of study drug Use of immunosuppressive drugs within 4 weeks prior to the first dose of study drug Require long-term steroid therapy or any other form of immunosuppressive therapy not including inhaled steroids Toxicity (excluding hair loss or fatigue) caused by previous antitumor therapy that did not recover to NCI CTCAE v 5.0 level 0-1 within 4 weeks prior to the first dose of study drug Received major surgery or has unhealed wounds, ulcers, or fractures within 4 weeks prior to the first dose of study drug Expect to receive other anti-tumor treatments during study (allowing palliative radiotherapy) History of infectious pneumonitis that required steroids or has current pneumonitis Known active untreated CNS metastases and/or spinal cord compression and/or cancerous meningitis, or with a history of soft meningeal cancer Active autoimmune disease that has required systemic treatment in past 2 years Known active Hepatitis B or Hepatitis C virus Uncontrolled concomitant diseases or neurological, psychiatric/social conditions that could affect study compliance, significantly increase the risk of adverse events, or affect the participant's ability to provide written informed consent Known history of human immunodeficiency virus (HIV) infection Known history of active tuberculosis (TB) or active syphilis History of allogeneic organ transplantation or hematopoietic stem cell transplantation Accompanied by uncontrolled third interstitial fluids requiring repeated drainage, such as pleural effusion, ascites, pericardial effusion, etc. Known severe allergic reactions to other monoclonal antibodies or are allergic to any IBI318 formulation component Female subjects who are pregnant or lactating

Ages Eligible for Study
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Minimum Age: 18 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: IBI318 DL1<br> | Biological: IBI318<br>* 0.3 mg intravenous infusion, C1D1 and afterwards Q2W<br>|
| Experimental: IBI318 DL2<br> | Biological: IBI318<br>* 1 mg intravenous infusion, C1D1 and afterwards Q2W<br>|
| Experimental: IBI318 DL3<br> | Biological: IBI318<br>* 3 mg intravenous infusion, C1D1 and afterwards Q2W<br>|
| Experimental: IBI318 DL4<br> | Biological: IBI318<br>* 10 mg intravenous infusion, C1D1 and afterwards Q2W<br>|
| Experimental: IBI318 DL5<br> | Biological: IBI318<br>* 30 mg intravenous infusion, C1D1 and afterwards Q2W<br>|
| Experimental: IBI318 DL6<br> | Biological: IBI318<br>* 100 mg intravenous infusion, C1D1 and afterwards Q2W<br>|
| Experimental: IBI318 DL7<br> | Biological: IBI318<br>* 300 mg intravenous infusion, C1D1 and afterwards Q2W<br>|
| Experimental: IBI318 DL8<br> | Biological: IBI318<br>* 600 mg intravenous infusion, C1D1 and afterwards Q2W<br>|
| Experimental: IBI318 DL7b<br> | Biological: IBI318<br>* Intravenous infusion, C1D1 and afterwards Q3W<br>|
| Experimental: IBI318 DL8b<br> | Biological: IBI318<br>* Intravenous infusion, C1D1 and afterwards Q3W<br>|
| Experimental: IBI318 RP2D<br> | Biological: IBI318<br>* Intravenous infusion Q3W<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants experiencing dose-limiting toxicities (DLTs) |  | 28 days within first dose in phase Ia | 
| Number of participants experiencing clinical and laboratory adverse events (AEs) |  | Up to 90 days post last dose | 
| Number of all study participants who demonstrate a tumor response |  | up to 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The area under the curve (AUC) of plasma concentration of drug against time after administration of IBI318 |  | Up to 90 days post last dose | 
| Maximum concentration (Cmax) after first dose interval of IBI318 |  | Up to 90 days post last dose | 
| Time at which maximum concentration (Tmax) occurs for IBI318 |  | Up to 90 days post last dose | 
| The half-life (t1/2) of IBI318 in plasma |  | Up to 90 days post last dose | 
| Positive rate of ADA and Nab |  | Up to 90 days post last dose |