Medical Oncology
Conditions
Keywords
Phase 1, Solid Tumors, FGFR2, Antibody drug conjugate
Brief summary
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)
Interventions
DRUGBAY1187982
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
Sponsors
Bayer
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* All subjects must be \>/= 18 years at the first screening examination / visit * Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 * Subjects with advanced, histologically or cytologically confirmed solid tumors described to express fibroblast growth factor receptor 2 (FGFR2) that are refractory to any standard therapy * For maximum tolerated dose (MTD) Dose Expansion: Subjects with advanced, histologically or cytologically confirmed triple-negative breast cancer who had undergone within 4 lines of systemic anti-cancer treatment and not eligible for standard therapy anymore. * Subjects need to have evaluable disease (measurable or not measurable). * Women of childbearing potential must have a negative pregnancy test performed within 7 days prior to the start of treatment
Exclusion criteria
* History of allergic reactions to monoclonal antibody therapy (or excipients in the formulation) * Anti-cancer chemotherapy, experimental cancer therapy including clinical trial, or cancer immunotherapy within 4 weeks prior to the first dose of the investigational drug. * Toxic effects of previous anti-cancer chemotherapy, experimental cancer therapy, or cancer immunotherapy have not normalized. * History of symptomatic metastatic brain or meningeal tumors unless the subject is longer than 3 months from the end of definitive therapy before the first dose of the investigational drug and has clinically or radiologically no evidence of tumor growth. * History of clinically significant cardiac disease * Congenital coagulation abnormalities * Subjects who are pregnant or are breast-feeding
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum tolerated dose(MTD) | Up to 2 years | 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 |
| Number of subjects with adverse events as a measure of safety and tolerability | Up to 2 years | — |
| Number of subjects with serious adverse events as a measure of safety and tolerability | Up to 2 years | — |
Secondary
| Measure | Time frame |
|---|---|
| AUC (area under the concentration vs. time curve from zero to infinity after single (first) | 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 |
| Cmax,md (maximum observed drug concentration in measured matrix after multiple dose administration during a dosage interval) | 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) | 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 | 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 |
| Cmax (maximum observed drug concentration in measured matrix after single dose administration) | 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 |
| CK18 levels in tumor tissue sample | 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 | 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 | Cycle 1: Day 1: before infusion (pre-dose), Day 8 |
| Tumor response | Screening, Day 15 (± 7 days) of Cycle 2 and every even subsequent Cycle (i.e. Cycles 2, 4, 6, 8, etc.) |
| FGFR2 levels in tumor tissue sample | Screening |
| AUC(0-tlast) AUC from time 0 to the last data point >LLOQ | 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) | 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 |
Countries
Singapore, South Korea, United States
Outcome results
None listed