Description:
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)
Title
- Brief Title: Phase I, Dose-escalation Trial of BAY1187982 in Subjects With Advanced Solid Tumors Known to Express Fibroblast Growth Factor Receptor 2 (FGFR2)
- Official Title: An Open-label,Phase I, Dose-escalation Trial to Evaluate the Safety, Tolerability, Maximum Tolerated Dose, Pharmacokinetic, and Pharmacodynamics of the Anti-FGFR2 Antibody Drug Conjugate BAY1187982 in Subjects With Advanced Solid Tumors Known to Express FGFR2.
Clinical Trial IDs
- ORG STUDY ID:
16897
- NCT ID:
NCT02368951
Conditions
Interventions
Drug | Synonyms | Arms |
---|
BAY1187982 | | BAY1187982 |
Purpose
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)
Trial Arms
Name | Type | Description | Interventions |
---|
BAY1187982 | Experimental | Dose-escalation phase:
Approximately 30 subjects will participate in the dose-escalation phase The total number of subjects will depend on the number of cohorts necessary to identify the MTD.
MTD expansion phase:
Once the MTD has been determined, two expansion cohorts in FGFR2 expressing indications are planned:
Cohort 1: Triple negative breast cancer (TNBC). This cohort will enroll 80 subjects (N=40 with low to moderate FGFR2 expression and N=40 with high FGFR2 expression) Cohort 2: Other indications expressing FGFR2. This cohort 40 subjects will be enrolled. | |
Eligibility Criteria
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
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Maximum tolerated dose(MTD) |
Time Frame: | Up to 2 years |
Safety Issue: | |
Description: | 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 |
Secondary Outcome Measures
Measure: | 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 |
Safety Issue: | |
Description: | |
Measure: | 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 |
Safety Issue: | |
Description: | |
Measure: | 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 |
Safety Issue: | |
Description: | |
Measure: | 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 |
Safety Issue: | |
Description: | |
Measure: | 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 |
Safety Issue: | |
Description: | |
Measure: | 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 |
Safety Issue: | |
Description: | |
Measure: | 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 |
Safety Issue: | |
Description: | |
Measure: | FGFR2 levels in tumor tissue sample |
Time Frame: | Screening |
Safety Issue: | |
Description: | |
Measure: | 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. |
Safety Issue: | |
Description: | |
Measure: | 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. |
Safety Issue: | |
Description: | |
Measure: | 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 |
Safety Issue: | |
Description: | |
Measure: | 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.) |
Safety Issue: | |
Description: | |
Details
Phase: | Phase 1 |
Primary Purpose: | Interventional |
Overall Status: | Terminated |
Lead Sponsor: | Bayer |
Trial Keywords
- Phase 1
- Solid Tumors
- FGFR2
- Antibody drug conjugate
Last Updated
July 12, 2017