Sym023 (Anti-TIM-3) in Patients With Advanced Solid Tumor... | NCT03489343 | Trialant
NCT03489343
Sponsor
Symphogen A/S
Status
Completed
Last Update Posted
Oct 12, 2021Actual
Enrollment
24Actual
Phase
Phase 1
Conditions
Metastatic Cancer
Solid Tumor
Lymphoma
Interventions
Sym023
Countries
United States
Canada
Protocol Section
Identification Module
NCT ID
Results Section
Participant Flow Module
Pre-assignment Details
Annotation Section
No data available
No data is available for this block.
Document Section
Large Document Module
Document Has No Statistical Analysis Plan (SAP)
Derived Section
Miscellaneous Info Module
Version Holder
NCT03489343
Obsolete or Duplicate NCT IDs
Not provided
Organization Study
Sym023-01
Secondary IDs
Not provided
Brief Title
Sym023 (Anti-TIM-3) in Patients With Advanced Solid Tumor Malignancies or Lymphomas
Official Title
A Phase 1, Open-Label, Multicenter Trial Investigating the Safety, Tolerability, and Preliminary Antineoplastic Activity of Sym023 (Anti-TIM-3) in Patients With Advanced Solid Tumor Malignancies or Lymphomas
Acronym
Not provided
Organization
Symphogen A/SINDUSTRY
Status Module
Record Verification Date
Aug 2021
Overall Recruitment Status or Expanded Access Status
Completed
Last Known Status
Not provided
Delayed Posting
Not provided
Why Stopped
Not provided
Expanded Access Info
No
Start Date
May 24, 2018Actual
Primary Completion Date
Jun 3, 2020Actual
Completion Date
Jun 3, 2020Actual
First Submitted Date
Mar 26, 2018
First Submission Date that Met QC Criteria
Apr 3, 2018
First Posted Date
Apr 5, 2018Actual
Results Waived
Not provided
Results First Submitted Date
Apr 27, 2021
Results First Submitted that Met QC Criteria
Oct 11, 2021
Results First Posted Date
Oct 12, 2021Actual
Certification/Extension (aka Delayed Results) First Submitted Date
Not provided
Certification/Extension First Submitted that Passed QC Review
Not provided
Certification/Extension First Posted Date
Not provided
Last Update Submitted Date
Oct 11, 2021
Last Update Posted Date
Oct 12, 2021Actual
Sponsor/Collaborators Module
Responsible Party, by Official Title
Sponsor
Lead Sponsor
Symphogen A/SINDUSTRY
Collaborators
Not provided
Oversight Module
Has Data Monitoring Committee (DMC)
No
Is FDA Regulated Drug
Yes
Is FDA Regulated Device
No
Is Unapproved Device
Not provided
Pediatric Postmarket Surveillance of a Device Product
Not provided
Product Exported from US
Not provided
FDAAA801 Violation
Not provided
Description Module
Brief Summary
This was the first study to test Sym023 in humans. The primary purpose of this study was to see if Sym023 is safe and tolerable for patients with locally advanced/unresectable or metastatic solid tumor malignancies or lymphomas that are refractory to available therapy or for which no standard therapy is available.
Detailed Description
This study evaluated the preliminary safety, tolerability, and dose-limiting toxicities (DLTs) of Sym023, a recombinant, fully human, anti-T-cell immunoglobulin and mucin-domain containing-3 (anti-TIM-3) monoclonal antibody (mAb). The goal was to establish the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of sequential escalating doses of Sym023 when administered once every 2 weeks (Q2W) by intravenous (IV) infusion to patient cohorts with locally advanced/unresectable or metastatic solid tumor malignancies or lymphomas that are refractory to available therapy or for which no standard therapy is available. If an MTD was not identified, a maximum administered dose (MAD) was to be determined. Sym023 was given to patients in escalating dose cohorts; each patient was given one fixed dose level.
Conditions Module
Conditions
Metastatic Cancer
Solid Tumor
Lymphoma
Keywords
Locally advanced/unresectable
Metastatic solid tumor
Lymphoma
Anti-TIM-3
TIM-3
TIM3
Design Module
Study Type
Interventional
Number of References to an Expanded Access Study
Not provided
Expanded Access Types
Not provided
Patient Registry
Not provided
Target Follow-Up Duration
Not provided
Phases
Phase 1
Interventional Study Design
Allocation
Biospecimen
No data available
No data is available for this block.
Enrollment
24Actual
Arms/Interventions Module
Arm Groups
Label
Type
Description
Intervention Names
Sym023 0.03 mg/kg
Experimental
Sym023 was administered at a dose of 0.03 mg/kg by intravenous infusion
Drug: Sym023
Sym023 0.1 mg/kg
Experimental
Sym023 was administered at a dose of 0.1 mg/kg by intravenous infusion
Drug: Sym023
Sym023 0.3 mg/kg
Experimental
Sym023 was administered at a dose of 0.3 mg/kg by intravenous infusion
Drug: Sym023
Sym023 1.0 mg/kg
Experimental
Sym023 was administered at a dose of 1.0 mg/kg by intravenous infusion
Drug: Sym023
Sym023 3.0 mg/kg
Experimental
Sym023 was administered at a dose of 3.0 mg/kg by intravenous infusion
Drug: Sym023
Sym023 10.0 mg/kg
Experimental
Sym023 was administered at a dose of 10.0 mg/kg by intravenous infusion
Interventions
Name
Type
Description
Arm Group Labels
Other Names
Sym023
Drug
Sym023 is a recombinant, fully human antibody that binds TIM-3 and induces activation of immune cells.
Assess the safety and tolerability of Sym023 on a Q2W (once every 2 weeks) schedule to establish the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D). Assessment based on the occurrence of AEs meeting DLT criteria measured during Cycle 1. The MTD was to be determined by those DLTs that occurred during C1 in either more than 1 patient in a 3 to 6 patient cohort or ≥33.3% of patients in the event of an expanded 7 to 12 patient cohort. One patient in the 10.0 mg/kg dose cohort was not evaluable for MTD as she did not complete C1 for a reason other than drug toxicity (i.e., discontinuation after 1 dose due to patient withdrawal of consent). However, this patient was included in the evaluation of other outcomes.
28 days
Secondary Outcomes
Measure
Description
Time Frame
Evaluation of the Immunogenicity of Sym023.
Serum sampling to assess the potential for anti-drug antibody (ADA) formation. The number of patients with positive samples at indicated visits is presented.
Baseline up to 6-months follow-up, approximately 1 year
Evaluation of Objective Response (OR) or Stable Disease (SD) by RECIST v1.1
Other Outcomes
Not provided
Eligibility Module
Eligibility Criteria
Inclusion Criteria:
Male or female patients, ≥ 18 years of age at the time of obtaining informed consent.
Documented (histologically- or cytologically-proven) solid tumor malignancy that is locally advanced or metastatic; patients with documented lymphomas.
Malignancy (solid tumor or lymphoma) that is currently not amenable to surgical intervention due to either medical contraindications or nonresectability of the tumor.
Refractory to or intolerant of existing therapy(ies) known to provide clinical benefit.
Measurable or non-measurable disease according to RECIST v1.1 or RECIL 2017.
Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1.
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.
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) and fertile men with WOCBP-partner(s) not using and not willing to use a highly effective method of contraception.
Known, untreated central nervous system (CNS) or leptomeningeal metastases, or spinal cord compression, patients with any of the above not controlled by prior surgery or radiotherapy, or patients with symptoms suggesting CNS involvement for which treatment is required.
Hematologic malignancies other than lymphomas.
Active thrombosis, or a history of deep vein thrombosis (DVT) or pulmonary embolism (PE) within 4 weeks prior to Cycle 1/Day 1 (C1/D1) unless adequately treated and considered stable.
Active uncontrolled bleeding or a known bleeding diathesis.
Clinically significant cardiovascular disease or condition.
Significant ocular disease or condition, including history of autoimmune or inflammatory disorder.
Significant pulmonary disease or condition.
Current or recent (within 6 months) significant gastrointestinal (GI) disease or condition.
An active, known, or suspected autoimmune disease, or a documented history of autoimmune disease or syndrome, requiring systemic steroids or other immunosuppressive medications.
History of significant toxicities associated with previous administration of immune checkpoint inhibitors that necessitated permanent discontinuation of that therapy.
Patients with unresolved > Grade 1 toxicity associated with any prior antineoplastic therapy, with exceptions.
Inadequate recovery from any prior surgical procedure, or having undergone any major surgical procedure within 4 weeks prior to C1/D1.
Known history of human immunodeficiency virus (HIV) or known active infection with hepatitis B virus (HBV) or hepatitis C virus (HCV).
Accepts Healthy Volunteers
No
Sex
All
Sex/Gender Based
Not provided
Sex/Gender Description
Not provided
Minimum Age
18 Years
Maximum Age
Not provided
Standard Ages
AdultOlder Adult
Study Population
Not provided
Sampling Method
Not provided
Contacts/Locations Module
Central Contacts
Not provided
Overall Officials
Name
Affiliation
Role
Lillian Siu, MD, FRCPC
Princess Margaret Cancer Centre
Principal Investigator
Locations
Facility
Status
City
State
ZIP
Country
Contacts
South Texas Accelerated Research Therapeutics (START) Midwest
Grand Rapids
Michigan
49503
United States
References Module
No data available
No data is available for this block.
IPD Sharing Statement Module
Plan to Share IPD
No
Description
Not provided
Types
Not provided
Time Frame
Not provided
Access Criteria
Not provided
URL
Not provided
Not provided
Recruitment Details
Not provided
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
FG000
Sym023 0.03 mg/kg
Sym023 0.03 mg/kg intravenous infusion once every 2 weeks
FG001
Sym023 0.1 mg/kg
Sym023 0.1 mg/kg intravenous infusion once every 2 weeks
FG002
Sym023 0.3 mg/kg
Sym023 0.3 mg/kg intravenous infusion once every 2 weeks
FG003
Sym023 1.0 mg/kg
Sym023 1.0 mg/kg intravenous infusion once every 2 weeks
FG004
Sym023 3.0 mg/kg
Sym023 3.0 mg/kg intravenous infusion once every 2 weeks
FG005
Sym023 10.0 mg/kg
Sym023 10.0 mg/kg intravenous infusion once every 2 weeks
FG006
Sym023 20.0 mg/kg
Sym023 20.0 mg/kg intravenous infusion once every 2 weeks
Periods
Title
Milestones
Reasons Not Completed
Overall Study
Type
Comment
Milestone Data
STARTED
FG0001 subjects
FG0011 subjects
FG0023 subjects
FG0033 subjects
FG0043 subjects
FG0057 subjects
FG0066 subjects
COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
NOT COMPLETED
FG0001 subjects
FG0011 subjects
FG0023 subjects
FG0033 subjects
FG004
Type
Comment
Reasons
Documented progressive disease
FG0001 subjects
FG0010 subjects
FG0023 subjects
FG003
Baseline Characteristics Module
Baseline Analysis Population Description
The full analysis set (FAS) comprised all consented patients who had received at least a fraction of 1 dose of study drug. The patients in the FAS contributed to the analyses as allocated to treatment.
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
BG000
Sym023 0.03 mg/kg
Sym023 0.03 mg/kg intravenous infusion once every 2 weeks
BG001
Sym023 0.1 mg/kg
Sym023 0.1 mg/kg intravenous infusion once every 2 weeks
Assess the safety and tolerability of Sym023 on a Q2W (once every 2 weeks) schedule to establish the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D). Assessment based on the occurrence of AEs meeting DLT criteria measured during Cycle 1. The MTD was to be determined by those DLTs that occurred during C1 in either more than 1 patient in a 3 to 6 patient cohort or ≥33.3% of patients in the event of an expanded 7 to 12 patient cohort. One patient in the 10.0 mg/kg dose cohort was not evaluable for MTD as she did not complete C1 for a reason other than drug toxicity (i.e., discontinuation after 1 dose due to patient withdrawal of consent). However, this patient was included in the evaluation of other outcomes.
DLT analysis set of patients who completed treatment dosing in a 4-week (28 day) period that was Cycle 1. One patient out of 7 patients in Group 10mg/kg did not complete Cycle 1 and are not included in the "participants analyzed"
Posted
Number
Number of DLTs
28 days
ID
Title
Description
Adverse Events Module
Frequency Threshold
2
Time Frame
24 months
Description
Only treatment-emergent adverse events (AEs) are presented in clinicaltrials.gov, defined as AEs with onset dates on or after the first dose of study medication or AEs that occurred before the first dose of study medication and increased in severity after the first dose of study medication up to the last dose of study drug plus 30 days.
All-Cause Mortality Comment
Not provided
Arm/Groups
ID
Title
Description
Deaths (Affected)
Deaths (At Risk)
Serious Events (Affected)
Serious Events (At Risk)
Other Events (Affected)
Other Events (At Risk)
EG000
Sym023 0.03 mg/kg
Sym023 0.03 mg/kg intravenous infusion once every 2 weeks
Sym023 was administered at a dose of 20.0 mg/kg by intravenous infusion
Drug: Sym023
Sym023 0.3 mg/kg
Sym023 1.0 mg/kg
Sym023 10.0 mg/kg
Sym023 20.0 mg/kg
Sym023 3.0 mg/kg
Anti-TIM-3
OR or SD Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1). The number of patients with confirmed or unconfirmed OR (partial or complete response) is presented. Duration of SD for patients with best overall response = SD was defined as the time from the day of first study treatment to the start of radiologic disease progression or death. If the patient did not have a radiological disease progression or death, the duration of SD was defined as the time from the day of first study treatment to the date of the last SD assessment.
24 months
Evaluation of Objective Response (OR) or Stable Disease (SD) by iRECIST
OR or SD Assessed by Immunotherapeutics Response Evaluation Criteria in Solid Tumors (iRECIST). The number of patients with confirmed or unconfirmed OR (partial or complete response) is presented. Duration of SD for patients with best overall response = SD was defined as the time from the day of first study treatment to the start of radiologic disease progression or death. If the patient did not have a radiological disease progression or death, the duration of SD was defined as the time from the day of first study treatment to the date of the last SD assessment.
24 months
Evaluation of Objective Response (OR) or Stable Disease (SD) by RECIL 2017.
OR or SD Assessed by Response Evaluation Criteria in Lymphomas 2017 (RECIL 2017)
24 months
Time to Progression (TTP) of Disease.
Based on time of enrollment to first evidence of progression on imaging studies, as assessed by RECIST v1.1, RECIL 2017, or iRECIST, depending on tumor type. The numbers shown below correspond to the values related to RECIST v1.1.
24 months
Area Under the Concentration-time Curve in a Dosing Interval (AUC).
The AUC after first dose was estimated using non-compartmental methods. Blood samples for PK analysis were taken at the following timepoints: before the start of the infusion, at the end of the infusion and at 2, 4, 8, 24, 48 and 168 hours after the end of the infusion. Actual timepoints were recorded.
From before the start of the infusion to 168 hours after the end of the infusion
Maximum Concentration (Cmax)
Outcome measure after first dose was derived from observed data. Blood samples for PK analysis were taken at the following timepoints: before the start of the infusion, at the end of the infusion and at 2, 4, 8, 24, 48 and 168 hours after the end of the infusion. Actual timepoints were recorded.
From before the start of the infusion to 168 hours after the end of the infusion
Time to Reach Maximum Concentration (Tmax)
Outcome measure after first dose was derived from observed data. Blood samples for PK analysis were taken at the following timepoints: before the start of the infusion, at the end of the infusion and at 2, 4, 8, 24, 48 and 168 hours after the end of the infusion. Actual timepoints were recorded.
From before the start of the infusion to 168 hours after the end of the infusion
Trough Concentration (Ctrough)
Outcome measure after first dose was derived from observed data. Blood samples for PK analysis were taken at the following timepoints: before the start of the infusion, at the end of the infusion and at 2, 4, 8, 24, 48 and 168 hours after the end of the infusion. Actual timepoints were recorded.
From before the start of the infusion to 168 hours after the end of the infusion
Terminal Elimination Half-life (T½)
Outcome measure after first dose was estimated using non-compartmental methods. Blood samples for PK analysis were taken at the following timepoints: before the start of the infusion, at the end of the infusion and at 2, 4, 8, 24, 48 and 168 hours after the end of the infusion. Actual timepoints were recorded.
From before the start of the infusion to 168 hours after the end of the infusion
Clearance (CL)
Outcome measure after first dose was estimated using non-compartmental methods. Blood samples for PK analysis were taken at the following timepoints: before the start of the infusion, at the end of the infusion and at 2, 4, 8, 24, 48 and 168 hours after the end of the infusion. Actual timepoints were recorded.
From before the start of the infusion to 168 hours after the end of the infusion
The University of Texas MD Anderson Cancer Center
Houston
Texas
77030
United States
NEXT Oncology
San Antonio
Texas
78240
United States
Princess Margaret Cancer Centre
Toronto
Ontario
M5G 2M9
Canada
0 subjects
FG0050 subjects
FG0060 subjects
3 subjects
FG0057 subjects
FG0066 subjects
1 subjects
FG0043 subjects
FG0055 subjects
FG0064 subjects
Adverse Event
FG0000 subjects
FG0011 subjects
FG0020 subjects
FG0030 subjects
FG0040 subjects
FG0051 subjects
FG0060 subjects
Withdrawal by Subject
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0031 subjects
FG0040 subjects
FG0051 subjects
FG0061 subjects
Clinical progression
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0031 subjects
FG0040 subjects
FG0050 subjects
FG0061 subjects
BG002
Sym023 0.3 mg/kg
Sym023 0.3 mg/kg intravenous infusion once every 2 weeks
BG003
Sym023 1.0 mg/kg
Sym023 1.0 mg/kg intravenous infusion once every 2 weeks
BG004
Sym023 3.0 mg/kg
Sym023 3.0 mg/kg intravenous infusion once every 2 weeks
BG005
Sym023 10.0 mg/kg
Sym023 10.0 mg/kg intravenous infusion once every 2 weeks
BG006
Sym023 20.0 mg/kg
Sym023 20.0 mg/kg intravenous infusion once every 2 weeks
BG007
Total
Total of all reporting groups
1
BG0011
BG0023
BG0033
BG0043
BG0057
BG0066
BG00724
Participants
Title
Denominators
Categories
Title
Measurements
<=18 years
BG0000
BG0010
BG0020
BG0030
BG0040
BG0050
BG0060
BG0070
Between 18 and 65 years
BG0001
BG0011
BG0022
BG0031
BG004
>=65 years
BG0000
BG0010
BG0021
BG0032
BG004
Age, Continuous
Median
Full Range
years
Title
Denominators
Categories
Title
Measurements
BG00064(64 to 64)
BG00164(64 to 64)
BG00262(59 to 67)
BG00366(45 to 70)
BG00471(59 to 72)
BG00554(37 to 76)
BG00661(36 to 74)
BG00763(36 to 76)
Sex: Female, Male
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Female
BG0000
BG0011
BG0022
BG0032
BG0043
BG0054
BG0064
BG00716
Male
BG0001
BG0010
BG0021
BG0031
BG004
Ethnicity (NIH/OMB)
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Hispanic or Latino
BG0000
BG0010
BG0020
BG0030
BG0040
BG0050
BG0060
BG0070
Not Hispanic or Latino
BG0001
BG0011
BG0023
BG0033
BG004
Unknown or Not Reported
BG0000
BG0010
BG0020
BG0030
BG004
Race (NIH/OMB)
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
American Indian or Alaska Native
BG0000
BG0010
BG0020
BG0030
BG0040
BG0050
BG0060
BG0070
Asian
BG0000
BG0010
BG0020
BG0030
BG004
Native Hawaiian or Other Pacific Islander
BG0000
BG0010
BG0020
BG0030
BG004
Black or African American
BG0000
BG0010
BG0020
BG0030
BG004
White
BG0001
BG0011
BG0023
BG0033
BG004
More than one race
BG0000
BG0010
BG0020
BG0030
BG004
Unknown or Not Reported
BG0000
BG0010
BG0020
BG0030
BG004
Region of Enrollment
Number
participants
Title
Denominators
Categories
Canada
Title
Measurements
BG0000
BG0010
BG0020
BG0031
BG0041
BG0052
BG0061
BG0075
United States
Title
Measurements
BG0001
BG0011
BG0023
BG003
ECOG PS
The ECOG PS is Eastern Cooperative Oncology Group performance status, and is a measure of how well a person is able to carry out ordinary daily activities while living with cancer, and provides an estimate of what treatments a person may tolerate. It has scores ranging from 0 to 5 with 0 being best and 5 being worst. ECOG is commonly used as a prognostic tool, as a selection criterion for cancer research, and to help determine treatment. Patients with an ECOG PS of 0 or 1 were included in the trial.
Count of Participants
Participants
Title
Denominators
Categories
1
Title
Measurements
BG0001
BG0011
BG0022
BG0032
BG0043
BG0056
BG0064
BG00719
0
Title
Measurements
BG0000
BG0010
BG0021
BG003
OG000
Sym023 0.03 mg/kg
Sym023 0.03 mg/kg intravenous infusion once every 2 weeks
OG001
Sym023 0.1 mg/kg
Sym023 0.1 mg/kg intravenous infusion once every 2 weeks
OG002
Sym023 0.3 mg/kg
Sym023 0.3 mg/kg intravenous infusion once every 2 weeks
OG003
Sym023 1.0 mg/kg
Sym023 1.0 mg/kg intravenous infusion once every 2 weeks
OG004
Sym023 3.0 mg/kg
Sym023 3.0 mg/kg intravenous infusion once every 2 weeks
OG005
Sym023 10.0 mg/kg
Sym023 10.0 mg/kg intravenous infusion once every 2 weeks
OG006
Sym023 20.0 mg/kg
Sym023 20.0 mg/kg intravenous infusion once every 2 weeks
Units
Counts
Participants
OG0001
OG0011
OG0023
OG0033
OG0043
OG0056
OG0066
Title
Denominators
Categories
Title
Measurements
OG0000
OG0010
OG0020
OG0030
OG0040
OG0050
OG0060
Secondary
Evaluation of the Immunogenicity of Sym023.
Serum sampling to assess the potential for anti-drug antibody (ADA) formation. The number of patients with positive samples at indicated visits is presented.
Full analysis set of all randomised and treated patients
Posted
Count of Participants
Participants
Baseline up to 6-months follow-up, approximately 1 year
ID
Title
Description
OG000
Sym023 0.03 mg/kg
Sym023 0.03 mg/kg intravenous infusion once every 2 weeks
OG001
Sym023 0.1 mg/kg
Sym023 0.1 mg/kg intravenous infusion once every 2 weeks
OG002
Sym023 0.3 mg/kg
Sym023 0.3 mg/kg intravenous infusion once every 2 weeks
OG003
Sym023 1.0 mg/kg
Sym023 1.0 mg/kg intravenous infusion once every 2 weeks
OG004
Sym023 3.0 mg/kg
Sym023 3.0 mg/kg intravenous infusion once every 2 weeks
OG005
Sym023 10.0 mg/kg
Sym023 10.0 mg/kg intravenous infusion once every 2 weeks
OG006
Sym023 20.0 mg/kg
Sym023 20.0 mg/kg intravenous infusion once every 2 weeks
Units
Counts
Participants
OG0001
OG0011
OG0023
OG003
Title
Denominators
Categories
Cycle 1 days 1 and 15
Title
Measurements
OG0000
OG0010
OG0020
OG003
Secondary
Evaluation of Objective Response (OR) or Stable Disease (SD) by RECIST v1.1
OR or SD Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1). The number of patients with confirmed or unconfirmed OR (partial or complete response) is presented. Duration of SD for patients with best overall response = SD was defined as the time from the day of first study treatment to the start of radiologic disease progression or death. If the patient did not have a radiological disease progression or death, the duration of SD was defined as the time from the day of first study treatment to the date of the last SD assessment.
Full analysis set of randomised and treated patients who was evaluable for response. One patient out of 7 in group 10mg/kg was not evaluable for response
Posted
Count of Participants
Participants
24 months
ID
Title
Description
OG000
Sym023 0.03 mg/kg
Sym023 0.03 mg/kg intravenous infusion once every 2 weeks
OG001
Sym023 0.1 mg/kg
Sym023 0.1 mg/kg intravenous infusion once every 2 weeks
OG002
Sym023 0.3 mg/kg
Sym023 0.3 mg/kg intravenous infusion once every 2 weeks
OG003
Sym023 1.0 mg/kg
Sym023 1.0 mg/kg intravenous infusion once every 2 weeks
OG004
Sym023 3.0 mg/kg
Sym023 3.0 mg/kg intravenous infusion once every 2 weeks
OG005
Sym023 10.0 mg/kg
Sym023 10.0 mg/kg intravenous infusion once every 2 weeks
OG006
Sym023 20.0 mg/kg
Sym023 20.0 mg/kg intravenous infusion once every 2 weeks
Units
Counts
Participants
OG0001
OG0011
OG0023
OG003
Title
Denominators
Categories
OR rate
Title
Measurements
OG0000
OG0010
OG0020
OG003
Secondary
Evaluation of Objective Response (OR) or Stable Disease (SD) by iRECIST
OR or SD Assessed by Immunotherapeutics Response Evaluation Criteria in Solid Tumors (iRECIST). The number of patients with confirmed or unconfirmed OR (partial or complete response) is presented. Duration of SD for patients with best overall response = SD was defined as the time from the day of first study treatment to the start of radiologic disease progression or death. If the patient did not have a radiological disease progression or death, the duration of SD was defined as the time from the day of first study treatment to the date of the last SD assessment.
Full analysis set of randomised and treated patients who were evaluable for response. One patient out of 7 in group 10mg/kg was not evaluable for response
Posted
Count of Participants
Participants
24 months
ID
Title
Description
OG000
Sym023 0.03 mg/kg
Sym023 0.03 mg/kg intravenous infusion once every 2 weeks
OG001
Sym023 0.1 mg/kg
Sym023 0.1 mg/kg intravenous infusion once every 2 weeks
OG002
Sym023 0.3 mg/kg
Sym023 0.3 mg/kg intravenous infusion once every 2 weeks
OG003
Sym023 1.0 mg/kg
Sym023 1.0 mg/kg intravenous infusion once every 2 weeks
OG004
Sym023 3.0 mg/kg
Sym023 3.0 mg/kg intravenous infusion once every 2 weeks
OG005
Sym023 10.0 mg/kg
Sym023 10.0 mg/kg intravenous infusion once every 2 weeks
OG006
Sym023 20.0 mg/kg
Sym023 20.0 mg/kg intravenous infusion once every 2 weeks
Units
Counts
Participants
OG0001
OG0011
OG0023
OG003
Title
Denominators
Categories
OR rate
Title
Measurements
OG0000
OG0010
OG0020
OG003
Secondary
Evaluation of Objective Response (OR) or Stable Disease (SD) by RECIL 2017.
OR or SD Assessed by Response Evaluation Criteria in Lymphomas 2017 (RECIL 2017)
No lymphomas were recorded in this trial, therefore it was not possible to do the RECIL evaluation.
Posted
24 months
ID
Title
Description
OG000
Sym023 0.03 mg/kg
Sym023 0.03 mg/kg intravenous infusion once every 2 weeks
OG001
Sym023 0.1 mg/kg
Sym023 0.1 mg/kg intravenous infusion once every 2 weeks
OG002
Sym023 0.3 mg/kg
Sym023 0.3 mg/kg intravenous infusion once every 2 weeks
OG003
Sym023 1.0 mg/kg
Sym023 1.0 mg/kg intravenous infusion once every 2 weeks
OG004
Sym023 3.0 mg/kg
Sym023 3.0 mg/kg intravenous infusion once every 2 weeks
OG005
Sym023 10.0 mg/kg
Sym023 10.0 mg/kg intravenous infusion once every 2 weeks
OG006
Sym023 20.0 mg/kg
Sym023 20.0 mg/kg intravenous infusion once every 2 weeks
Units
Counts
Participants
OG0000
OG0010
OG0020
OG003
Secondary
Time to Progression (TTP) of Disease.
Based on time of enrollment to first evidence of progression on imaging studies, as assessed by RECIST v1.1, RECIL 2017, or iRECIST, depending on tumor type. The numbers shown below correspond to the values related to RECIST v1.1.
The full analysis set of randomized and treated patients who were evaluable for response. One patient out of 7 in group 10mg/kg was not evaluable for response or time to progression (TTP) as the patient left trial due to Adverse Event
Posted
Median
Full Range
months
24 months
ID
Title
Description
OG000
Sym023 0.03 mg/kg
Sym023 0.03 mg/kg intravenous infusion once every 2 weeks
OG001
Sym023 0.1 mg/kg
Sym023 0.1 mg/kg intravenous infusion once every 2 weeks
OG002
Sym023 0.3 mg/kg
Sym023 0.3 mg/kg intravenous infusion once every 2 weeks
OG003
Sym023 1.0 mg/kg
Sym023 1.0 mg/kg intravenous infusion once every 2 weeks
OG004
Sym023 3.0 mg/kg
Sym023 3.0 mg/kg intravenous infusion once every 2 weeks
OG005
Sym023 10.0 mg/kg
Sym023 10.0 mg/kg intravenous infusion once every 2 weeks
OG006
Sym023 20.0 mg/kg
Sym023 20.0 mg/kg intravenous infusion once every 2 weeks
Units
Counts
Participants
OG0001
OG0011
OG0023
OG003
Title
Denominators
Categories
Title
Measurements
OG0001.81(1.81 to 1.81)
OG0017.89(7.89 to 7.89)
OG0021.18(0.72 to 1.38)
OG003
Secondary
Area Under the Concentration-time Curve in a Dosing Interval (AUC).
The AUC after first dose was estimated using non-compartmental methods. Blood samples for PK analysis were taken at the following timepoints: before the start of the infusion, at the end of the infusion and at 2, 4, 8, 24, 48 and 168 hours after the end of the infusion. Actual timepoints were recorded.
Pharmacokinetic analysis set (same as the full analysis set) of all randomised and treated patients
Posted
Mean
Full Range
h*μg/mL
From before the start of the infusion to 168 hours after the end of the infusion
ID
Title
Description
OG000
Sym023 0.03 mg/kg
Sym023 0.03 mg/kg intravenous infusion once every 2 weeks
OG001
Sym023 0.1 mg/kg
Sym023 0.1 mg/kg intravenous infusion once every 2 weeks
OG002
Sym023 0.3 mg/kg
Sym023 0.3 mg/kg intravenous infusion once every 2 weeks
OG003
Sym023 1.0 mg/kg
Sym023 1.0 mg/kg intravenous infusion once every 2 weeks
OG004
Sym023 3.0 mg/kg
Sym023 3.0 mg/kg intravenous infusion once every 2 weeks
OG005
Sym023 10.0 mg/kg
Sym023 10.0 mg/kg intravenous infusion once every 2 weeks
OG006
Sym023 20.0 mg/kg
Sym023 20.0 mg/kg intravenous infusion once every 2 weeks
Units
Counts
Participants
OG0001
OG0011
OG0023
OG003
Title
Denominators
Categories
Title
Measurements
OG00070(70 to 70)
OG001176(176 to 176)
OG002878(680 to 1158)
OG003
Secondary
Maximum Concentration (Cmax)
Outcome measure after first dose was derived from observed data. Blood samples for PK analysis were taken at the following timepoints: before the start of the infusion, at the end of the infusion and at 2, 4, 8, 24, 48 and 168 hours after the end of the infusion. Actual timepoints were recorded.
Pharmacokinetic analysis set (same as the full analysis set) of all randomised and treated patients
Posted
Mean
Full Range
μg/mL
From before the start of the infusion to 168 hours after the end of the infusion
ID
Title
Description
OG000
Sym023 0.03 mg/kg
Sym023 0.03 mg/kg intravenous infusion once every 2 weeks
OG001
Sym023 0.1 mg/kg
Sym023 0.1 mg/kg intravenous infusion once every 2 weeks
OG002
Sym023 0.3 mg/kg
Sym023 0.3 mg/kg intravenous infusion once every 2 weeks
OG003
Sym023 1.0 mg/kg
Sym023 1.0 mg/kg intravenous infusion once every 2 weeks
OG004
Sym023 3.0 mg/kg
Sym023 3.0 mg/kg intravenous infusion once every 2 weeks
OG005
Sym023 10.0 mg/kg
Sym023 10.0 mg/kg intravenous infusion once every 2 weeks
OG006
Sym023 20.0 mg/kg
Sym023 20.0 mg/kg intravenous infusion once every 2 weeks
Units
Counts
Participants
OG0001
OG0011
OG0023
OG003
Title
Denominators
Categories
Title
Measurements
OG0000.85(0.85 to 0.85)
OG0011.98(1.98 to 1.98)
OG0027.94(5.67 to 11.56)
OG003
Secondary
Time to Reach Maximum Concentration (Tmax)
Outcome measure after first dose was derived from observed data. Blood samples for PK analysis were taken at the following timepoints: before the start of the infusion, at the end of the infusion and at 2, 4, 8, 24, 48 and 168 hours after the end of the infusion. Actual timepoints were recorded.
Pharmacokinetic analysis set (same as the full analysis set) of all randomised and treated patients
Posted
Mean
Full Range
hours
From before the start of the infusion to 168 hours after the end of the infusion
ID
Title
Description
OG000
Sym023 0.03 mg/kg
Sym023 0.03 mg/kg intravenous infusion once every 2 weeks
OG001
Sym023 0.1 mg/kg
Sym023 0.1 mg/kg intravenous infusion once every 2 weeks
OG002
Sym023 0.3 mg/kg
Sym023 0.3 mg/kg intravenous infusion once every 2 weeks
OG003
Sym023 1.0 mg/kg
Sym023 1.0 mg/kg intravenous infusion once every 2 weeks
OG004
Sym023 3.0 mg/kg
Sym023 3.0 mg/kg intravenous infusion once every 2 weeks
OG005
Sym023 10.0 mg/kg
Sym023 10.0 mg/kg intravenous infusion once every 2 weeks
OG006
Sym023 20.0 mg/kg
Sym023 20.0 mg/kg intravenous infusion once every 2 weeks
Units
Counts
Participants
OG0001
OG0011
OG0023
OG003
Title
Denominators
Categories
Title
Measurements
OG0004.5(4.5 to 4.5)
OG0010.6(0.6 to 0.6)
OG0021.2(0.5 to 2.5)
OG003
Secondary
Trough Concentration (Ctrough)
Outcome measure after first dose was derived from observed data. Blood samples for PK analysis were taken at the following timepoints: before the start of the infusion, at the end of the infusion and at 2, 4, 8, 24, 48 and 168 hours after the end of the infusion. Actual timepoints were recorded.
Pharmacokinetic analysis set (same as the full analysis set) of all randomized and treated patients. Data for cohort 0.03mg/kg: Ctrough at 168 hours were below the limit of quantification, hence no reported data
Posted
Mean
Full Range
μg/mL
From before the start of the infusion to 168 hours after the end of the infusion
ID
Title
Description
OG000
Sym023 0.03 mg/kg
Sym023 0.03 mg/kg intravenous infusion once every 2 weeks
OG001
Sym023 0.1 mg/kg
Sym023 0.1 mg/kg intravenous infusion once every 2 weeks
OG002
Sym023 0.3 mg/kg
Sym023 0.3 mg/kg intravenous infusion once every 2 weeks
OG003
Sym023 1.0 mg/kg
Sym023 1.0 mg/kg intravenous infusion once every 2 weeks
OG004
Sym023 3.0 mg/kg
Sym023 3.0 mg/kg intravenous infusion once every 2 weeks
OG005
Sym023 10.0 mg/kg
Sym023 10.0 mg/kg intravenous infusion once every 2 weeks
OG006
Sym023 20.0 mg/kg
Sym023 20.0 mg/kg intravenous infusion once every 2 weeks
Units
Counts
Participants
OG0001
OG0011
OG0023
OG003
Title
Denominators
Categories
Title
Measurements
OG000NA(NA to NA)Ctrough at 168 hours were below the limit of quantification, hence no reported data
OG0010.16(0.16 to 0.16)
OG0021.26(0.76 to 1.85)
Secondary
Terminal Elimination Half-life (T½)
Outcome measure after first dose was estimated using non-compartmental methods. Blood samples for PK analysis were taken at the following timepoints: before the start of the infusion, at the end of the infusion and at 2, 4, 8, 24, 48 and 168 hours after the end of the infusion. Actual timepoints were recorded.
Pharmacokinetic analysis set (same as the full analysis set) of all randomised and treated patients. Data for cohort 0.03mg/kg: T½ could not be accurately calculated due to few datapoint within the elimination period
Posted
Mean
Full Range
hours
From before the start of the infusion to 168 hours after the end of the infusion
ID
Title
Description
OG000
Sym023 0.03 mg/kg
Sym023 0.03 mg/kg intravenous infusion once every 2 weeks
OG001
Sym023 0.1 mg/kg
Sym023 0.1 mg/kg intravenous infusion once every 2 weeks
OG002
Sym023 0.3 mg/kg
Sym023 0.3 mg/kg intravenous infusion once every 2 weeks
OG003
Sym023 1.0 mg/kg
Sym023 1.0 mg/kg intravenous infusion once every 2 weeks
OG004
Sym023 3.0 mg/kg
Sym023 3.0 mg/kg intravenous infusion once every 2 weeks
OG005
Sym023 10.0 mg/kg
Sym023 10.0 mg/kg intravenous infusion once every 2 weeks
OG006
Sym023 20.0 mg/kg
Sym023 20.0 mg/kg intravenous infusion once every 2 weeks
Units
Counts
Participants
OG0001
OG0011
OG0023
OG003
Title
Denominators
Categories
Title
Measurements
OG000NAT½ could not be accurately calculated due to few datapoints within the elimination
OG001105.10(105.10 to 105.10)
OG002153.49(136.70 to 164.11)
Secondary
Clearance (CL)
Outcome measure after first dose was estimated using non-compartmental methods. Blood samples for PK analysis were taken at the following timepoints: before the start of the infusion, at the end of the infusion and at 2, 4, 8, 24, 48 and 168 hours after the end of the infusion. Actual timepoints were recorded.
Pharmacokinetic analysis set (same as the full analysis set) of all randomized and treated patients. Data for cohort 0.03mg/kg: Clearence could not be accurately calculated since too few datapoint within the elimination period
Posted
Mean
Full Range
mL/h)/kg
From before the start of the infusion to 168 hours after the end of the infusion
ID
Title
Description
OG000
Sym023 0.03 mg/kg
Sym023 0.03 mg/kg intravenous infusion once every 2 weeks
OG001
Sym023 0.1 mg/kg
Sym023 0.1 mg/kg intravenous infusion once every 2 weeks
OG002
Sym023 0.3 mg/kg
Sym023 0.3 mg/kg intravenous infusion once every 2 weeks
OG003
Sym023 1.0 mg/kg
Sym023 1.0 mg/kg intravenous infusion once every 2 weeks
OG004
Sym023 3.0 mg/kg
Sym023 3.0 mg/kg intravenous infusion once every 2 weeks
OG005
Sym023 10.0 mg/kg
Sym023 10.0 mg/kg intravenous infusion once every 2 weeks
OG006
Sym023 20.0 mg/kg
Sym023 20.0 mg/kg intravenous infusion once every 2 weeks
Units
Counts
Participants
OG0000
OG0011
OG0021
OG003
Title
Denominators
Categories
Title
Measurements
OG0010.501(0.501 to 0.501)
OG0020.364(0.364 to 0.364)
OG0040.582(0.582 to 0.582)
1
0
1
1
1
EG001
Sym023 0.1 mg/kg
Sym023 0.1 mg/kg intravenous infusion once every 2 weeks
0
1
1
1
1
1
EG002
Sym023 0.3 mg/kg
Sym023 0.3 mg/kg intravenous infusion once every 2 weeks
3
3
0
3
3
3
EG003
Sym023 1.0 mg/kg
Sym023 1.0 mg/kg intravenous infusion once every 2 weeks
0
3
0
3
3
3
EG004
Sym023 3.0 mg/kg
Sym023 3.0 mg/kg intravenous infusion once every 2 weeks
2
3
0
3
3
3
EG005
Sym023 10.0 mg/kg
Sym023 10.0 mg/kg intravenous infusion once every 2 weeks
1
7
2
7
7
7
EG006
Sym023 20.0 mg/kg
Sym023 20.0 mg/kg intravenous infusion once every 2 weeks