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

Study Overview
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Brief Summary
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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)

Official Title
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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.

Conditions
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Medical Oncology

Intervention / Treatment
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* Drug: BAY1187982


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BAY1187982<br>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. | Drug: BAY1187982<br>* 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<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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)0-504 (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-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 | 
| FGFR2 levels in tumor tissue sample |  | Screening | 
| 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.) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Phase 1, Solid Tumors, FGFR2, Antibody drug conjugate