The primary purpose of this study is to see if Sym021 is safe and tolerable as monotherapy, in combination with either Sym022 or Sym023, and in Combination with both Sym022 and Sym023 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.
Part 1 of this study will evaluate the safety, tolerability, and dose-limiting toxicities (DLTs) to establish the maximum tolerated dose (MTD) and/or the selected dose of sequential escalating doses of Sym021 when administered once every 2 weeks (Q2W) by 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 Part 2 of the study will evaluate the safety, tolerability, and DLTs to establish the MTD and/or the selected dose of sequential escalating doses of Sym022 when administered Q2W in combination with a fixed dose of 3 mg/kg of Sym021, each by 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 Part 3 of the study will evaluate of the safety, tolerability, and DLTs to establish the MTD and/or the selected dose of sequential escalating doses of Sym023 when administered Q2W in combination with fixed doses of 3 mg/kg of Sym021 and either 1, 3 or 5 mg/kg of Sym022, each by 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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
89
Sym021 is a humanized antibody that binds PD-1 with sub-nanomolar affinity and blocks binding of the inhibitory ligands PD-L1 and PD-L2, thus releasing PD-1-mediated inhibition of the immune response.
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.
Sym023 is a recombinant, fully human antibody that binds TIM-3 and induces activation of immune cells.
South Texas Accelerated Research Therapeutics (START) Midwest
Grand Rapids, Michigan, United States
The University of Texas MD Anderson Cancer Center
Houston, Texas, United States
NEXT Oncology
San Antonio, Texas, United States
Princess Margaret Cancer Centre
Toronto, Ontario, Canada
Part 1: Assessment of treatment emergent adverse events (AEs) meeting DLT criteria.
Assess the safety and tolerability of Sym021 monotherapy on a Q2W schedule. Assessment based on the occurrence of AEs meeting DLT criteria measured during Cycle 1.
Time frame: 12 months
Part 2: Assessment of treatment emergent adverse events (AEs) meeting DLT criteria.
Assess the safety and tolerability of the Sym021 RP2D in combination with sequential escalating doses of Sym022 or Sym023 on a Q2W schedule. Assessment based on the occurrence of AEs meeting DLT criteria measured during Cycle 1.
Time frame: 12 months
Part 3: Assessment of treatment emergent adverse events (AEs) meeting DLT criteria.
Assess the safety and tolerability of the Sym021 RP2D in combination with sequential escalating doses of Sym022 and Sym023 on a Q2W schedule. Assessment based on the occurrence of AEs meeting DLT criteria measured during Cycle 1.
Time frame: 12 months
Evaluation of the immunogenicity of Sym021 as a single agent and in combination with Sym022 and Sym023.
Serum sampling to assess the potential for anti-drug antibody (ADA) formation.
Time frame: 24 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.
Time frame: 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.
Time frame: 24 months
Area under the concentration-time curve in a dosing interval (AUC)
Will be estimated using non-compartmental methods and actual timepoints.
Time frame: 24 months
Maximum concentration (Cmax)
Will be derived from observed data.
Time frame: 24 months
Time to reach maximum concentration (Tmax)
Will be derived from observed data.
Time frame: 24 months
Trough concentration (Ctrough)
Will be derived from observed data.
Time frame: 24 months
Terminal elimination half-life (T½)
Will be estimated using non-compartmental methods and actual timepoints.
Time frame: 24 months
Clearance (CL)
Will be estimated using non-compartmental methods and actual timepoints.
Time frame: 24 months
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