Phase I Dose Escalation Study of BAY 1163877 (Rogaratinib) in Japanese Subjects With Refractory, Locally Advanced or Metastatic Solid Tumors

An Open Label, Phase I Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Efficacy of BAY 1163877 in Japanese Subjects With Refractory, Locally Advanced or Metastatic Solid Tumors

Primary objectives of this study are to assess the safety and tolerability of BAY 1163877 in Japanese subjects with refractory, locally advanced or metastatic solid tumors and to characterize the PK of BAY 1163877

Inclusion Criteria:

• Japanese males or female aged ≥ 20 years
• Histologically or cytologically confirmed refractory, locally advanced or metastatic solid tumors who are not candidates for standard therapy at discretion of investigator
• High FGFR expression levels based on archival or fresh tumor biopsy specimen analysis. Bladder cancer subjects with low overall FGFR expression levels can be included if activating FGFR3 mutations are confirmed.
• Subjects must have at least one measurable or evaluable lesion according to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1).
• Life expectancy of at least 3 months
• Recovery to National Cancer Institute's Common Terminology Criteria for Adverse Events, version 4.03 (CTCAE v4.03) Grade < 2 level or recovery to baseline preceding the prior treatment from any previous drug / procedure-related toxicity (subjects with persistent alopecia, anemia, and/or hypothyroidism can be included)
• Eastern Cooperative Oncology Group performance status (ECOG PS) of 0-2
• Adequate bone marrow, liver and renal function
• Prothrombin time-International normalized ratio (PT-INR) and activated partial thromboplastin time (APTT) ≤ 1.5 times ULN. Subjects being treated with anticoagulant, e.g. warfarin or heparin, will be allowed to participate provided no prior evidence of an underlying abnormality in these parameters exists

Exclusion Criteria:

• History or current condition of an uncontrolled cardiovascular disease including congestive heart failure New York Heart Association (NYHA) > Class 2, unstable angina (symptoms of angina at rest) or new-onset angina (within last 3 months) or myocardial infarction within past 6 months and cardiac arrhythmias requiring anti-arrhythmic therapy (beta-blockers or digoxin are permitted)
• Left ventricular ejection fraction (LVEF) < 50% as assessed by echocardiography performed
• 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). Calcium (Ca) x (time) phosphate (PO4) should be < 70 mg²/dL².
• 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.
• Moderate or severe hepatic impairment (subjects with Child-Pugh score B or C cannot be included.)
• Known human immunodeficiency virus (HIV) infection
• Subjects with an active hepatitis B and/or C infection requiring treatment
• Anticancer chemotherapy or immunotherapy during the study or within 5-half-lives of anticancer chemotherapy or immunotherapy before start of study treatment.
• Systolic blood pressure ≤ 110 and pulse rate ≥ 100/min, or diastolic blood pressure ≤ 70 mmHg and pulse rate ≥ 100/min
• Uncontrolled hypertension as indicated by a resting systolic BP ≥160 mmHg or diastolic BP ≥100 mmHg at screening