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

Medical Oncology Clinical Trial

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 Details — Status: Terminated

Administrative data

• NCT number: NCT02368951
• Other study ID #: 16897
• Status: Terminated
• Phase: Phase 1
• First received: February 16, 2015
• Last updated: July 10, 2017
• Start date: March 24, 2015
• Est. completion date: July 27, 2016

Study information

• Verified date: July 2017
• Source: Bayer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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)

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 20
• Est. completion date: July 27, 2016
• Est. primary completion date: July 27, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Medical Oncology

Intervention

Drug:
• BAY1187982
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

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Bayer

Countries where clinical trial is conducted

United States,  Korea, Republic of,  Singapore, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Up to 2 years
Primary	Number of subjects with adverse events as a measure of safety and tolerability		Up to 2 years
Primary	Number of subjects with serious adverse events as a measure of safety and tolerability		Up to 2 years
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	FGFR2 levels in tumor tissue sample		Screening
Secondary	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.
Secondary	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.
Secondary	Development of anti-drug antibodies (ADAs) in plasma as an indicator of immunogenicity		Cycle 1: Day 1: before infusion (pre-dose), Day 8
Secondary	Tumor response		Screening, Day 15 (± 7 days) of Cycle 2 and every even subsequent Cycle (i.e. Cycles 2, 4, 6, 8, etc.)

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