Phase I, Dose-escalation Trial of BAY1187982 in Subjects With Advanced Solid Tumors Known to Express Fibroblast Growth Factor Receptor 2 (FGFR2)

Phase 1

Terminated

• Conditions: Medical Oncology
• Interventions: Drug: BAY1187982

• Registration Number: NCT02368951
• Lead Sponsor: Bayer

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)

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2015-02-16
• Study First Submitted QC: 2015-02-16
• Study First Posted: 2015-02-23
• Study Start: 2015-03-24
• Primary Completion: 2016-07-27
• Study Completion: 2016-07-27
• Status Verified: 2017-07
• Last Update Submitted: 2017-07-10
• Last Update Posted: 2017-07-12

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 20

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
BAY1187982	BAY1187982	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.

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
FGFR2 levels in tumor tissue sample	Screening
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
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-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 (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
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(0-504)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
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.
Tumor response	Screening, Day 15 (± 7 days) of Cycle 2 and every even subsequent Cycle (i.e. Cycles 2, 4, 6, 8, etc.)
Development of anti-drug antibodies (ADAs) in plasma as an indicator of immunogenicity	Cycle 1: Day 1: before infusion (pre-dose), Day 8