To evaluate the safety, tolerability, maximum tolerated dose, pharmacokinetics, and pharmacodynamics of the anti-FGFR2 antibody drug conjugate BAY1187982 in subjects with advanced solid tumors known to express fibroblast growth factor receptor 2 (FGFR2)
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
20
A dose of 0.1 mg BAY 1187982 per kilogram (kg) body weight (BW) was chosen as the starting dose based on toxicology data. The investigational drug will be administered as a 1-hour IV infusion once every 21 days at the trial site (Day 1 of each 21-day Cycle). The maximum possible dose escalation will be 2-fold and not more than 0.5 mg/kg BW until maximum tolerated dose is selected
Unnamed facility
San Francisco, California, United States
Unnamed facility
Santa Monica, California, United States
Unnamed facility
New Haven, Connecticut, United States
Maximum tolerated dose(MTD)
The MTD is defined as the maximum dose at which the incidence of DLTs during Cycle 1 is below 20%, or the maximum dose administered, whichever is achieved first during dose escalation
Time frame: Up to 2 years
Number of subjects with adverse events as a measure of safety and tolerability
Time frame: Up to 2 years
Number of subjects with serious adverse events as a measure of safety and tolerability
Time frame: Up to 2 years
Cmax (maximum observed drug concentration in measured matrix after single dose administration)
Time frame: Cycles 1 and 3, Day 1: pre-dose, end of infusion, Day 2, Day 3, Day 5, Day 8, and Day 15.Cycles 2 and 4: Day 1: pre-dose.Cycle 5 Day 1 and every odd cycles after: pre-dose and end of infusion
AUC(0-tlast) AUC from time 0 to the last data point >LLOQ
Time frame: Cycles 1 and 3, Day 1: pre-dose, end of infusion, Day 2, Day 3, Day 5, Day 8, and Day 15.Cycles 2 and 4: Day 1: pre-dose.Cycle 5 Day 1 and every odd cycles after: pre-dose and end of infusion
AUC)0-504 (AUC from zero to 504 hours post infusion)
Time frame: Cycles 1 and 3, Day 1: pre-dose, end of infusion, Day 2, Day 3, Day 5, Day 8, and Day 15.Cycles 2 and 4: Day 1: pre-dose.Cycle 5 Day 1 and every odd cycles after: pre-dose and end of infusion
AUC (area under the concentration vs. time curve from zero to infinity after single (first)
Time frame: Cycles 1 and 3, Day 1: pre-dose, end of infusion, Day 2, Day 3, Day 5, Day 8, and Day 15.Cycles 2 and 4: Day 1: pre-dose.Cycle 5 Day 1 and every odd cycles after: pre-dose and end of infusion
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Unnamed facility
Chicago, Illinois, United States
Unnamed facility
Baltimore, Maryland, United States
Unnamed facility
St Louis, Missouri, United States
Unnamed facility
New York, New York, United States
Unnamed facility
Nashville, Tennessee, United States
Unnamed facility
Houston, Texas, United States
Unnamed facility
Seattle, Washington, United States
...and 3 more locations
Cmax,md (maximum observed drug concentration in measured matrix after multiple dose administration during a dosage interval)
Time frame: Cycles 1 and 3, Day 1: pre-dose, end of infusion, Day 2, Day 3, Day 5, Day 8, and Day 15.Cycles 2 and 4: Day 1: pre-dose.Cycle 5 Day 1 and every odd cycles after: pre-dose and end of infusion
AUC(0-tlast)md (AUC from time 0 to the last data point >LLOQ after multiple dosing)
Time frame: Cycles 1 and 3, Day 1: pre-dose, end of infusion, Day 2, Day 3, Day 5, Day 8, and Day 15.Cycles 2 and 4: Day 1: pre-dose.Cycle 5 Day 1 and every odd cycles after: pre-dose and end of infusion
AUC(0-504)md
Time frame: Cycles 1 and 3, Day 1: pre-dose, end of infusion, Day 2, Day 3, Day 5, Day 8, and Day 15.Cycles 2 and 4: Day 1: pre-dose.Cycle 5 Day 1 and every odd cycles after: pre-dose and end of infusion
FGFR2 levels in tumor tissue sample
Time frame: Screening
CK18 levels in tumor tissue sample
Time frame: Screening, Cycles 1 and 3, Day 1: pre-dose, end of infusion, Day 2, Day 3, Day 5, Day 8, and Day 15.Cycles 2 and 4: Day 1: pre-dose and end of infusion.
Nucleosome level in plasma
Time frame: Screening, Cycles 1 and 3, Day 1: pre-dose, end of infusion, Day 2, Day 3, Day 5, Day 8, and Day 15.Cycles 2 and 4: Day 1: pre-dose and end of infusion.
Development of anti-drug antibodies (ADAs) in plasma as an indicator of immunogenicity
Time frame: Cycle 1: Day 1: before infusion (pre-dose), Day 8
Tumor response
Time frame: Screening, Day 15 (± 7 days) of Cycle 2 and every even subsequent Cycle (i.e. Cycles 2, 4, 6, 8, etc.)