Clinical trial NCT02368951: 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.
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Medical Oncology
Keywords: Phase 1
Solid Tumors
FGFR2
Antibody drug conjugate
Lead sponsor: Bayer
Sponsor class: INDUSTRY
First posted: 2015-02-23
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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)


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

Primary outcomes:
measure: Maximum tolerated dose(MTD)
timeFrame: Up to 2 years
measure: Number of subjects with adverse events as a measure of safety and tolerability
timeFrame: Up to 2 years
measure: Number of subjects with serious adverse events as a measure of safety and tolerability
timeFrame: Up to 2 years
Secondary outcomes:
measure: Cmax (maximum observed drug concentration in measured matrix after single dose administration)
timeFrame: 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
measure: AUC(0-tlast) AUC from time 0 to the last data point >LLOQ
timeFrame: 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
measure: AUC)0-504 (AUC from zero to 504 hours post infusion)
timeFrame: 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
measure: AUC (area under the concentration vs. time curve from zero to infinity after single (first)
timeFrame: 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
measure: Cmax,md (maximum observed drug concentration in measured matrix after multiple dose administration during a dosage interval)
timeFrame: 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
measure: AUC(0-tlast)md (AUC from time 0 to the last data point >LLOQ after multiple dosing)
timeFrame: 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
measure: AUC(0-504)md
timeFrame: 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
measure: FGFR2 levels in tumor tissue sample
timeFrame: Screening
measure: CK18 levels in tumor tissue sample
timeFrame: 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.
measure: Nucleosome level in plasma
timeFrame: 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.
measure: Development of anti-drug antibodies (ADAs) in plasma as an indicator of immunogenicity
timeFrame: Cycle 1: Day 1: before infusion (pre-dose), Day 8
measure: Tumor response
timeFrame: Screening, Day 15 (± 7 days) of Cycle 2 and every even subsequent Cycle (i.e. Cycles 2, 4, 6, 8, etc.)
Other outcomes:
Locations:
city: San Francisco
country: United States
state: California
city: Santa Monica
country: United States
state: California
city: New Haven
country: United States
state: Connecticut
city: Chicago
country: United States
state: Illinois
city: Baltimore
country: United States
state: Maryland
city: Saint Louis
country: United States
state: Missouri
city: New York
country: United States
state: New York
city: Nashville
country: United States
state: Tennessee
city: Houston
country: United States
state: Texas
city: Seattle
country: United States
state: Washington
city: Seoul
country: Korea, Republic of
city: Seoul
country: Korea, Republic of
city: Singapore
country: Singapore
Study officials:
affiliation: Bayer
name: Bayer Study Director
role: STUDY_DIRECTOR
References:
citation: Kim SB, Meric-Bernstam F, Kalyan A, Babich A, Liu R, Tanigawa T, Sommer A, Osada M, Reetz F, Laurent D, Wittemer-Rump S, Berlin J. First-in-Human Phase I Study of Aprutumab Ixadotin, a Fibroblast Growth Factor Receptor 2 Antibody-Drug Conjugate (BAY 1187982) in Patients with Advanced Cancer. Target Oncol. 2019 Oct;14(5):591-601. doi: 10.1007/s11523-019-00670-4.