Patient case: 67-year-old female with Breast cancer. Genetic variant: FGFR1 Amplification, PTEN (Q171). Other conditions: Depression, Hypertension, Heart Disease.

Clinical trial: Phase I Dose Escalation Pan-FGFR (Fibroblast Growth Factor Receptor) Inhibitor

Summary: -  This is the first study where BAY1163877 is given to humans. Impact of the study is to evaluate if patients with advanced solid cancers show advanced clinical benefit under the treatment with the pan FGFR inhibitor. Patients (all comers) will receive the study drug treatment in a dose-escalation scheme (no placebo group) to determine the safety, tolerability and maximum tolerated dose (MTD) of BAY1163877. The relative bioavailability of liquid service formulation and tablets will be determined.
  -  After the MTD is defined patients with solid tumors (all comers), lung cancer (lung adenocarcinoma & squamous non-small cell lung cancer), head and neck cancer or bladder cancer will be enrolled according to their FGFR expression profile (biomarker stratification).
  -  The study will also assess the pharmacokinetics, biomarker status, pharmacodynamic parameters and tumor response of BAY1163877.
  -  BAY1163877 will be given twice daily as oral application. Treatment will be stopped if the tumor continues to grow, if side effects, which the patient cannot tolerate, occur or if the patient decides to exit treatment.


Eligibility: Inclusion Criteria:
  -  For dose escalation: Subjects with any type of solid tumor (all comer) will be eligible for dose escalation and dose expansion at MTD in Part 1; Subjects enrolled for dose expansion (MTD expansion cohort "all comer") will be stratified according to high fibroblast growth factor receptor (FGFR) expression levels / FGFR mutation using archival or fresh tumor biopsy material
  -  For expansion cohorts: Subjects will be eligible for Part 2 only if they have histological or cytological confirmed squamous non-small cell lung cancer (sqNSCLC), lung adenocarcinoma, head and neck cancer or bladder cancer (BC). All subjects in Part 2 will be stratified according to high FGFR expression levels FGFR mutation using archival or fresh tumor biopsy specimen. BC subjects with low overall FGFR expression levels can be included if activating FGFR3(FGFR tyrosine kinases3) mutations are confirmed
  -  Subjects must have measurable disease (Response evaluation criteria in solid tumors (RECIST 1.1))
  -  Eastern Cooperative Oncology Group (ECOG) Performance Status 0 - 2
  -  Bone marrow, liver and renal functions as assessed by adequate laboratory methods to be conducted within 7 days prior to starting study Treatment
  -  Glomerular filtration rate (GFR) ≥ 30 mL/min/1.73 m2 according to the modified diet in renal disease (MDRD) abbreviated formula
  Exclusion Criteria:
  -  Previous treatment with anti-FGFR directed therapies (e.g. receptor tyrosine kinase inhibitors or FGFR-specific antibodies)
  -  Concomitant therapies that cannot be discontinued or switched to a different medication prior to study entry that are known to increase serum phosphate levels are not permitted within 4 weeks prior to start of study treatment)
  -  Anticancer chemotherapy or immunotherapy during the study or within 5-halflives prior to start of study treatment. Mitomycin C, nitrosoureas or monoclonal antibodies with anticancer activity (e.g. bevacizumab or cetuximab etc.) should not be given within 6 weeks before starting to receive study treatment or within 6 weeks of pre-treatment biopsy for biomarker (p-ERK1/2) studies

Relevance to patient case: not relevant