A Phase 1, Open-label, Multicenter, Dose Escalation Study of IBI363 (PD1-IL2m) in Subjects With Advanced Solid Malignancies or Lymphomas

Study Overview
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Brief Summary
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This is a Phase 1, open-label, multicenter, dose-escalation study designed to evaluate the safety, tolerability, and DLTs to establish the maximum tolerated dose (MTD) or maximum administered dose (MAD), and the RP2D of sequential doses of IBI363 (study drug) in subjects with advanced, refractory solid malignancies or lymphomas.

Official Title
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A Phase 1, Open-label, Multicenter, Dose Escalation Study of IBI363 (PD1-IL2m) in Subjects With Advanced Solid Malignancies or Lymphomas

Conditions
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Solid Malignancies or Lymphomas

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 Subjects with a documented (histologically- or cytologically-proven) solid tumor malignancy that is locally advanced or metastatic; subjects with documented lymphomas Subjects with a malignancy (solid tumor or lymphoma) that is currently not amenable to surgical intervention due to either medical contraindications or non-resectability of the tumor Subjects who are refractory to or intolerant to existing therapy(ies) known to provide clinical benefit 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 measurable or non-measurable disease according to RECIST v1.1 or standard criteria for lymphoma (Lugano 2014) Subjects, both male and female, who are either not of childbearing potential or who agree to use a highly effective method of contraception during the study beginning within 2 weeks prior to the first dose and continuing until 6 months after the last dose of study drug Subjects with the ability to understand and give written informed consent for participation in this trial, including all evaluations and procedures as specified by this protocol Exclusion Criteria: Women who are pregnant or lactating, or intending to become pregnant before, during, or within 6 months after the last dose of study drug. Women of childbearing potential (WOCBP) or fertile men with WOCBP partner(s), not using and not willing to use a highly effective method of contraception. 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.

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 |
| --- | --- | --- |
| Incidence of serious adverse events (SAEs), treatment-emergent AEs (TEAEs) and immune-related AEs (irAEs) | 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, mean corpuscular volume (MCV), white blood cell (WBC) count, platelets, 5-part differential white cell count, mean platelet volume 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 | 
| Number of dose-limiting toxicity (DLT) | Incidence of dose-limiting toxicity (DLT) events | 28 days during the first 4-week cycle | 

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 area under the curve (AUC) will be determined when appropriate. | Up to 2 years | 
| half-life (t1/2) of IBI363 | 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 per RECIST v1.1 for subjects with solid tumors, and per Lugano 2014 for subjects with lymphomas | 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 | 
| survival rates (6-month and 1-year) | 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 |