Phase I Dose Escalation Pan-FGFR (Fibroblast Growth Factor Receptor) Inhibitor
Conditions: Keywords
Phase I, Dose escalation, refractory, locally advanced or metastatic solid tumor, Bladder cancer, squamous non-small cell lung cancer, pan-FGFR inhibitor, lung adenocarcinoma, head and neck cancer
Study Type
Study Phase
Phase 1
Study Design
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Name: BAY1163877
Type: Drug
Overall Status
- 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.
Criteria for eligibility
Healthy Volunteers: No
Maximum Age: N/A
Minimum Age: 18 Years
Gender: Both
Criteria: 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

Exclusion Criteria:

- Previous treatment with anti-FGFR directed therapies (e.g. receptor tyrosine kinase inhibitors or FGFR-specific antibodies)

- Subjects with history and / or current evidence of endocrine alteration of calcium phosphate homeostasis (e.g. parathyroid disorder, history of parathyroidectomy, tumor lysis, tumoral calcinosis)

- Prior pancreatitis, intra- or extrahepatic biliary obstruction within the previous 12 months, or history of malignant obstruction requiring biliary stent unless stably treated with no prior obstruction or blockage of stent

- Pericarditis

- Current evidence of corneal disorder / keratopathy including but not limited to bullous / band keratopathy, corneal abrasion, inflammation / ulceration, keratoconjunctivitis etc. (to be confirmed by ophthalmologic examination). Pre-existing cataract is not an exclusion criterion.

- Concomitant therapies that cannot be discontinued or switched to a different medication prior to study entry that are known to increase serum calcium and / or phosphate levels, especially calcium, phosphate, vitamin D, parathyroid hormone (parathormone) are not permitted within 4 weeks prior to start of study treatment). Bisphosphonates, zolendronic acid or monoclonal anti-RANK ligand antibodies (denosumab) are allowed.

- Anticancer chemotherapy or immunotherapy during the study or within 5-half-lives prior to start of study treatment. Mitomycin C or nitrosoureas should not be given within 6 weeks of start of study treatment
Lyon Cedex, France
Status: Recruiting
Würzburg, Bayern, Germany
Status: Recruiting
Essen, Nordrhein-Westfalen, Germany
Status: Recruiting
Köln, Nordrhein-Westfalen, Germany
Status: Recruiting
Seoul, Korea, Republic of
Status: Recruiting
Seoul, Korea, Republic of
Status: Recruiting
Singapore, Singapore
Status: Recruiting
Singapore, Singapore
Status: Recruiting
Barcelona, Spain
Status: Recruiting
St. Gallen, Sankt Gallen, Switzerland
Status: Recruiting
Start Date
December 2013
Completion Date
August 2016
Record processing date processed this data on July 28, 2015 page