Safety, Tolerability and Preliminary Efficacy of IBI363 in Subjects With Advanced Solid Tumors or Lymphoma

Study Overview
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Brief Summary
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This study is an open-label, multicenter, phase Ia/Ib study. The study will evaluate the safety, tolerability and preliminary efficacy of IBI363 in subjects with advanced, relapsed or metastatic solid tumors or lymphoma, determine the maximum tolerated dose (MTD) or maximum administered dose (MAD), and thus determine the recommended phase 2 dose (RP2D).

Detailed Description
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This study is an open-label, multicenter, phase Ia/Ib study. The study will evaluate the safety, tolerability and preliminary efficacy of IBI363 in subjects with advanced, relapsed or metastatic solid tumors or lymphoma, determine the maximum tolerated dose (MTD) or maximum administered dose (MAD), and thus determine the recommended phase 2 dose (RP2D). The phase Ia part consists of the dose escalation and PD marker exploration part. The phase Ib part consists of the dose expansion part.

Official Title
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A Phase Ia/Ib Study to Evaluate the Safety, Tolerability and Preliminary Efficacy of IBI363 in Subjects With Advanced Solid Tumors or Lymphoma

Conditions
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Solid Tumors or Lymphoma

Intervention / Treatment
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* Biological: IBI363


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female subjects, ≥ 18 years Histologically or cytologically confirmed, unresectable locally advanced or metastatic solid tumors or lymphomas Subjects who progressed or are intolerant to existing standard therapy or subjects without standard therapy Note: Subjects may have received and failed prior therapy with a PD-1/PD-L1 inhibitor and be considered eligible for this trial. Subjects with at least one measurable lesion according to RECIST v1.1 for solid tumor or Lugano 2014 for lymphoma Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1. Expected survival time ≥ 3 months. Exclusion Criteria: Subjects with history of or known active seizure disorder, brain metastases, spinal cord compression, or carcinomatous meningitis, or new evidence of brain or leptomeningeal disease. Subjects with active thrombosis, or a history of deep vein thrombosis (DVT) or pulmonary embolism (PE) within 4 weeks prior to first administration of study drug unless adequately treated and considered by the Investigator to be stable. Active uncontrolled bleeding or a known bleeding diathesis. Subjects with massive pleural effusion or massive ascites.

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: IBI363<br>Single arm | Biological: IBI363<br>* a mutated IL-2 cytokine fused to an anti-PD-1 antibody to combine IL-2 pathway stimulation with checkpoint blockade.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of dose-limiting toxicity (DLT) | Incidence of dose-limiting toxicity (DLT) events | 21 days during the first 3-week cycle | 
| incidence of adverse enents (AE), serious adverse events (SAEs), treatment-emergent AEs (TEAEs) and immune-related AEs (irAEs) | AE is defined as an unexpected medical problem that happens during treatment with a drug or other therapy. An SAE is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly/birth defect or is an important medical event that may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed before. A TEAE will be defined as any new AE that begins, or any pre-existing condition that worsens in severity, after at least 1 dose of study treatment has been administered. irAEs will be assessed. | up to 90 days after the last administration | 
| Number of participants with abnormality in vital signs | Blood pressure, pulse, respiratory rate, and temperature will be assessed. | up to 90 days after the last administration | 
| Number of participants with abnormality in hematology parameters | Blood samples will be collected to evaluate hemoglobin, white blood cell (WBC) count, platelets and coagulation factors including international normalized ratio (INR), activated partial thromboplastin time (aPTT) and prothrombin time (PT) | up to 90 days after the last administration | 
| Number of participants with abnormality in clinical chemistry parameters | Blood samples will be collected to evaluate sodium, potassium, calcium, magnesium, chloride, glucose, creatinine, urea or blood urea nitrogen (BUN), bicarbonate, amylase, bilirubin, alkaline phosphatase, aspartate aminotransferase (AST), alanine aminotransferase (ALT), total protein, albumin, lactate dehydrogenase and lipase. | up to 90 days after the last administration | 
| Number of participants with abnormality in routine urinalysis parameters | Urine samples will be collected to evaluate specific gravity, leucocyte esterase, nitrite, blood, bilirubin, protein, glucose, ketones and urobilinogen. | up to 90 days after the last administration | 
| Number of participants with abnormality in ECG parameters | 12-lead ECG will be obtained using an ECG machine. Participants will be in supine or a semi-recumbent position (about 30 degrees of elevation) and rested for approximately 2 minutes before ECGs are recorded. | up to 90 days after the last administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| maximum concentration (Cmax) | PK parameters to be evaluated for IBI363 including maximum concentration (Cmax) will be determined when appropriate. | Up to 2 years | 
| area under the curve (AUC) | PK parameters to be evaluated for IBI363 including area under the curve (AUC) will be determined when appropriate. | Up to 2 years | 
| clearance (CL) | PK parameters to be evaluated for IBI363 including clearance (CL) will be determined when appropriate. | Up to 2 years | 
| half-life (t1/2) of IBI363 | PK parameters to be evaluated for IBI363 including half-life (t1/2) will be determined when appropriate. | Up to 2 years | 
| volume of distribution (V) | PK parameters to be evaluated for IBI363 including volume of distribution (V) will be determined when appropriate. | Up to 2 years | 
| Objective response rate (ORR) | To evaluate the preliminary antitumor activity of IBI363 | Up to 2 years | 
| time to response (TTR) | To evaluate the preliminary antitumor activity of IBI363 | Up to 2 years | 
| duration of response (DoR) | To evaluate the preliminary antitumor activity of IBI363 | Up to 2 years | 
| disease control rate (DCR) | To evaluate the preliminary antitumor activity of IBI363 | Up to 2 years | 
| progression-free survival (PFS) | To evaluate the preliminary antitumor activity of IBI363 | Up to 2 years | 
| 6-month and 1-year PFS rate | To evaluate the preliminary antitumor activity of IBI363 | Up to 2 years | 
| Overall survival (OS) | To evaluate the preliminary antitumor activity of IBI363 | through study completion, an average of 1 year | 
| 6-month and 1-year OS rate | To evaluate the preliminary antitumor activity of IBI363 | Up to 2 years | 
| The incidence of ADA and NAb of IBI363 | Each subject will be tested for anti-drug (IBI363) antibody (ADA), and ADA-positive serum samples will continue to be tested for neutralizing antibodies (NAb). | Up to 2 years |