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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
40
a mutated IL-2 cytokine fused to an anti-PD-1 antibody to combine IL-2 pathway stimulation with checkpoint blockade.
Kate.Wilkinson1@health.nsw.gov.au
Sydney, New South Wales, Australia
Westmead Hospital
Sydney, New South Wales, Australia
Sydney Southwest Private Hospital
Sydney, New South Wales, Australia
Cancer Care Wollongong
Sydney, New South Wales, Australia
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.
Time frame: 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.
Time frame: 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)
Time frame: 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.
Time frame: up to 90 days after the last administration
Number of participants with abnormality in routine urinalysis parameters
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Urine samples will be collected to evaluate specific gravity, leucocyte esterase, nitrite, blood, bilirubin, protein, glucose, ketones and urobilinogen.
Time frame: 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.
Time frame: up to 90 days after the last administration
Number of dose-limiting toxicity (DLT)
Incidence of dose-limiting toxicity (DLT) events
Time frame: 28 days during the first 4-week cycle
maximum concentration (Cmax)
PK parameters to be evaluated for IBI363 including maximum concentration (Cmax) will be determined when appropriate.
Time frame: 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.
Time frame: Up to 2 years
clearance (CL)
PK parameters to be evaluated for IBI363 including area under the curve (AUC) will be determined when appropriate.
Time frame: 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.
Time frame: Up to 2 years
Objective response rate (ORR)
To evaluate the preliminary antitumor activity of IBI363
Time frame: Up to 2 years
time to response (TTR)
To evaluate the preliminary antitumor activity of IBI363
Time frame: Up to 2 years
duration of response (DoR)
To evaluate the preliminary antitumor activity of IBI363
Time frame: Up to 2 years
disease control rate (DCR)
To evaluate the preliminary antitumor activity of IBI363
Time frame: Up to 2 years
progression-free survival (PFS)
To evaluate the preliminary antitumor activity of IBI363
Time frame: 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
Time frame: Up to 2 years
Overall survival (OS)
To evaluate the preliminary antitumor activity of IBI363
Time frame: through study completion, an average of 1 year
survival rates (6-month and 1-year)
To evaluate the preliminary antitumor activity of IBI363
Time frame: 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).
Time frame: Up to 2 years