Clinical Trials /

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

NCT02368951

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)

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Terminated

Phase:

Phase 1

Trial Eligibility

Document

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

  • Medical Oncology

Interventions

DrugSynonymsArms
BAY1187982BAY1187982

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

NameTypeDescriptionInterventions
BAY1187982ExperimentalDose-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.
  • BAY1187982

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