Back to resultsA Phase 1, Open-label, Multicenter, Dose Escalation Study of IBI363 (PD1-IL2m) in Subjects With Advanced Solid Malignancies or Lymphomas
Primary Purpose
Solid Malignancies or Lymphomas
Status
Recruiting
Phase
Phase 1
Locations
Australia
Study Type
Interventional
Intervention
IBI363
Sponsored by
About this trial
This is an interventional treatment trial for Solid Malignancies or Lymphomas
Eligibility Criteria
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.
Sites / Locations
- Southern Medical Day Care CentreRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
IBI363
Arm Description
Single arm
Outcomes
Primary Outcome Measures
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.
Number of participants with abnormality in vital signs
Blood pressure, pulse, respiratory rate, and temperature will be assessed.
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)
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.
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.
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.
Number of dose-limiting toxicity (DLT)
Incidence of dose-limiting toxicity (DLT) events
Secondary Outcome Measures
maximum concentration (Cmax)
PK parameters to be evaluated for IBI363 including maximum concentration (Cmax) will be determined when appropriate.
area under the curve (AUC)
PK parameters to be evaluated for IBI363 including area under the curve (AUC) will be determined when appropriate.
clearance (CL)
PK parameters to be evaluated for IBI363 including area under the curve (AUC) will be determined when appropriate.
half-life (t1/2) of IBI363
PK parameters to be evaluated for IBI363 including volume of distribution (V) will be determined when appropriate.
Objective response rate (ORR)
To evaluate the preliminary antitumor activity of IBI363
time to response (TTR)
To evaluate the preliminary antitumor activity of IBI363
duration of response (DoR)
To evaluate the preliminary antitumor activity of IBI363
disease control rate (DCR)
To evaluate the preliminary antitumor activity of IBI363
progression-free survival (PFS)
To evaluate the preliminary antitumor activity of IBI363
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
Overall survival (OS)
To evaluate the preliminary antitumor activity of IBI363
survival rates (6-month and 1-year)
To evaluate the preliminary antitumor activity of IBI363
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).
Full Information
NCT ID
NCT05290597
First Posted
January 9, 2022
Last Updated
September 4, 2022
Sponsor
Innovent Biologics (Suzhou) Co. Ltd.
1. Study Identification
Unique Protocol Identification Number
NCT05290597
Brief Title
A Phase 1, Open-label, Multicenter, Dose Escalation Study of IBI363 (PD1-IL2m) in Subjects With Advanced Solid Malignancies or Lymphomas
Official Title
A Phase 1, Open-label, Multicenter, Dose Escalation Study of IBI363 (PD1-IL2m) in Subjects With Advanced Solid Malignancies or Lymphomas
Study Type
Interventional
2. Study Status
Record Verification Date
September 2022
Overall Recruitment Status
Recruiting
Study Start Date
August 22, 2022 (Actual)
Primary Completion Date
June 30, 2023 (Anticipated)
Study Completion Date
August 31, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Innovent Biologics (Suzhou) Co. Ltd.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Solid Malignancies or Lymphomas
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
84 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
IBI363
Arm Type
Experimental
Arm Description
Single arm
Intervention Type
Biological
Intervention Name(s)
IBI363
Intervention Description
a mutated IL-2 cytokine fused to an anti-PD-1 antibody to combine IL-2 pathway stimulation with checkpoint blockade.
Primary Outcome Measure Information:
Title
Incidence of serious adverse events (SAEs), treatment-emergent AEs (TEAEs) and immune-related AEs (irAEs)
Description
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
Title
Number of participants with abnormality in vital signs
Description
Blood pressure, pulse, respiratory rate, and temperature will be assessed.
Time Frame
up to 90 days after the last administration
Title
Number of participants with abnormality in hematology parameters
Description
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
Title
Number of participants with abnormality in clinical chemistry parameters
Description
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
Title
Number of participants with abnormality in routine urinalysis parameters
Description
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
Title
Number of participants with abnormality in ECG parameters
Description
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
Title
Number of dose-limiting toxicity (DLT)
Description
Incidence of dose-limiting toxicity (DLT) events
Time Frame
28 days during the first 4-week cycle
Secondary Outcome Measure Information:
Title
maximum concentration (Cmax)
Description
PK parameters to be evaluated for IBI363 including maximum concentration (Cmax) will be determined when appropriate.
Time Frame
Up to 2 years
Title
area under the curve (AUC)
Description
PK parameters to be evaluated for IBI363 including area under the curve (AUC) will be determined when appropriate.
Time Frame
Up to 2 years
Title
clearance (CL)
Description
PK parameters to be evaluated for IBI363 including area under the curve (AUC) will be determined when appropriate.
Time Frame
Up to 2 years
Title
half-life (t1/2) of IBI363
Description
PK parameters to be evaluated for IBI363 including volume of distribution (V) will be determined when appropriate.
Time Frame
Up to 2 years
Title
Objective response rate (ORR)
Description
To evaluate the preliminary antitumor activity of IBI363
Time Frame
Up to 2 years
Title
time to response (TTR)
Description
To evaluate the preliminary antitumor activity of IBI363
Time Frame
Up to 2 years
Title
duration of response (DoR)
Description
To evaluate the preliminary antitumor activity of IBI363
Time Frame
Up to 2 years
Title
disease control rate (DCR)
Description
To evaluate the preliminary antitumor activity of IBI363
Time Frame
Up to 2 years
Title
progression-free survival (PFS)
Description
To evaluate the preliminary antitumor activity of IBI363
Time Frame
Up to 2 years
Title
6-month and 1-year PFS rate per RECIST v1.1 for subjects with solid tumors, and per Lugano 2014 for subjects with lymphomas
Description
To evaluate the preliminary antitumor activity of IBI363
Time Frame
Up to 2 years
Title
Overall survival (OS)
Description
To evaluate the preliminary antitumor activity of IBI363
Time Frame
through study completion, an average of 1 year
Title
survival rates (6-month and 1-year)
Description
To evaluate the preliminary antitumor activity of IBI363
Time Frame
Up to 2 years
Title
The incidence of ADA and NAb of IBI363
Description
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Min Luo
Phone
00861087412310
Email
min.luo@innoventbio.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Morteza Aghmesheh
Organizational Affiliation
Southern Medical Day Care Centre
Official's Role
Principal Investigator
Facility Information:
Facility Name
Southern Medical Day Care Centre
City
Wollongong
State/Province
New South Wales
ZIP/Postal Code
2500
Country
Australia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Morteza Aghmesheh
Phone
0061242225200
Email
Morteza.Aghmesheh@health.nsw.gov.au
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
A Phase 1, Open-label, Multicenter, Dose Escalation Study of IBI363 (PD1-IL2m) in Subjects With Advanced Solid Malignancies or Lymphomas
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