This is the first study to test Sym022 in humans. The primary purpose of this study is to see if Sym022 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.
This study will evaluate the preliminary safety, tolerability, and dose-limiting toxicities (DLTs) of Sym022, an anti-lymphocyte activation gene 3 (anti-LAG-3) monoclonal antibody (mAb). The goal is to establish the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of sequential escalating doses of Sym022 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 is not identified, a maximum administered dose (MAD) will be determined. Sym022 will be given to patients in escalating dose cohorts; each patient will be given one fixed dose level.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
15
Sym022 is a recombinant, fully human antibody that binds LAG-3 and blocks the LAG-3/major histocompatibility complex class II (MHC-II) interaction, thus allowing for increased T-cell proliferation and cytokine production.
South Texas Accelerated Research Therapeutics (START) Midwest
Grand Rapids, Michigan, United States
The University of Texas MD Anderson Cancer Center
Houston, Texas, United States
Princess Margaret Cancer Centre
Toronto, Ontario, Canada
Assessment of Treatment Related Adverse Events (AEs).
Assess the safety, tolerability and dose-limiting toxicities of Sym022 on a Q2W schedule to establish the MTD and/or RP2D.
Time frame: 19 months
Evaluation of the Immunogenicity of Sym022.
Serum sampling and incidence (%) per dose level to assess the potential for anti-drug antibody (ADA) formation. Count of participants show the number of participants who were tested positive for anti-Sym022 ADA.
Time frame: 19 months
Evaluation of Objective Response (OR) or Stable Disease (SD).
Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1), Response Evaluation Criteria in Lymphomas 2017 (RECIL 2017), or Immunotherapeutics Response Evaluation Criteria in Solid Tumors (iRECIST), depending on tumor type. The numbers shown below correspond to the values related to RECIST v1.1.
Time frame: 13 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.
Time frame: 13 months
Area Under the Concentration-time Curve in a Dosing Interval (AUC).
Will be estimated using non-compartmental methods and actual timepoints.
Time frame: 19 months
Maximum Concentration (Cmax)
Will be derived from observed data.
Time frame: 0, 2, 4, 8, 24, 48, 168 hours and 336 hours as administered Q2W (every second week)
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Time to Reach Maximum Concentration (Tmax)
Will be derived from observed data.
Time frame: 0, 2, 4, 8, 24, 48, 168 hours and 336 hours as administered Q2W (every second week)
Trough Concentration (Ctrough)
Will be derived from observed data.
Time frame: 0, 2, 4, 8, 24, 48, 168 hours and 336 hours as administered Q2W (every second week)
Terminal Elimination Half-life (T½)
Will be estimated using non-compartmental methods and actual timepoints.
Time frame: 0, 2, 4, 8, 24, 48, 168 hours and 336 hours as administered Q2W (every second week)
Clearance (CL)
Will be estimated using non-compartmental methods and actual timepoints.
Time frame: 0, 2, 4, 8, 24, 48, 168 hours and 336 hours as administered Q2W (every second week)