Solid Tumors or Lymphoma
Conditions
Brief summary
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
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.
Interventions
BIOLOGICALIBI363
a mutated IL-2 cytokine fused to an anti-PD-1 antibody to combine IL-2 pathway stimulation with checkpoint blockade.
Sponsors
Innovent Biologics (Suzhou) Co. Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Male or female subjects, ≥ 18 years 2. Histologically or cytologically confirmed, unresectable locally advanced or metastatic solid tumors or lymphomas 3. 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. 4. Subjects with at least one measurable lesion according to RECIST v1.1 for solid tumor or Lugano 2014 for lymphoma 5. Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1. 6. Expected survival time ≥ 3 months.
Exclusion criteria
1. 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. 2. 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. 3. Active uncontrolled bleeding or a known bleeding diathesis. 4. Subjects with massive pleural effusion or massive ascites.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of dose-limiting toxicity (DLT) | 21 days during the first 3-week cycle | Incidence of dose-limiting toxicity (DLT) events |
| incidence of adverse enents (AE), serious adverse events (SAEs), treatment-emergent AEs (TEAEs) and immune-related AEs (irAEs) | up to 90 days after the last administration | 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. |
| Number of participants with abnormality in vital signs | up to 90 days after the last administration | Blood pressure, pulse, respiratory rate, and temperature will be assessed. |
| Number of participants with abnormality in hematology parameters | up to 90 days after the last administration | 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) |
| Number of participants with abnormality in clinical chemistry parameters | up to 90 days after the last administration | 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. |
| Number of participants with abnormality in routine urinalysis parameters | up to 90 days after the last administration | Urine samples will be collected to evaluate specific gravity, leucocyte esterase, nitrite, blood, bilirubin, protein, glucose, ketones and urobilinogen. |
| Number of participants with abnormality in ECG parameters | up to 90 days after the last administration | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| duration of response (DoR) | Up to 2 years | To evaluate the preliminary antitumor activity of IBI363 |
| disease control rate (DCR) | Up to 2 years | To evaluate the preliminary antitumor activity of IBI363 |
| progression-free survival (PFS) | Up to 2 years | To evaluate the preliminary antitumor activity of IBI363 |
| maximum concentration (Cmax) | Up to 2 years | PK parameters to be evaluated for IBI363 including maximum concentration (Cmax) will be determined when appropriate. |
| Overall survival (OS) | through study completion, an average of 1 year | To evaluate the preliminary antitumor activity of IBI363 |
| 6-month and 1-year OS rate | Up to 2 years | To evaluate the preliminary antitumor activity of IBI363 |
| The incidence of ADA and NAb of IBI363 | Up to 2 years | 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). |
| 6-month and 1-year PFS rate | Up to 2 years | To evaluate the preliminary antitumor activity of IBI363 |
| area under the curve (AUC) | Up to 2 years | PK parameters to be evaluated for IBI363 including area under the curve (AUC) will be determined when appropriate. |
| clearance (CL) | Up to 2 years | PK parameters to be evaluated for IBI363 including clearance (CL) will be determined when appropriate. |
| half-life (t1/2) of IBI363 | Up to 2 years | PK parameters to be evaluated for IBI363 including half-life (t1/2) will be determined when appropriate. |
| volume of distribution (V) | Up to 2 years | PK parameters to be evaluated for IBI363 including volume of distribution (V) will be determined when appropriate. |
| Objective response rate (ORR) | Up to 2 years | To evaluate the preliminary antitumor activity of IBI363 |
| time to response (TTR) | Up to 2 years | To evaluate the preliminary antitumor activity of IBI363 |
Countries
China
Contacts
Primary ContactXiuzhi Yu
Outcome results
None listed