An Open-label Phase I Study of Orally Available Novel Small-molecule Fibroblast Growth Factor Receptors (FGFR) 1,2,3 and 4 Inhibitor, ASP5878 at Single and Multiple Doses in Patients With Solid Tumors

An Open-label Phase I Study of Oral ASP5878 at Single and Multiple Doses in Patients With Solid Tumors

The objectives of this study are to determine the tolerability, safety, pharmacokinetics (PK), pharmacodynamics (PD), and efficacy of oral ASP5878 in participants with solid tumors.

This study consists of two parts. In the dose-escalation part, ASP5878 (orally available novel small-molecule FGFR 1,2,3 and 4 inhibitor, multiple dosing once-a-day (q.d.), multiple dosing twice-a-day (b.i.d.) or 5-day on/2-day off dosing twice-a-day (5on-2off)) is administered to participants with solid tumors in an increasing dose manner, and the tolerability, safety, pharmacokinetics (PK), pharmacodynamics (PD) and efficacy of ASP5878 are evaluated in these participants. Cycle 0 consists of 3 days and Cycle 1 and subsequent cycles consist of 28 days each in the dose-escalation part. In the expansion part, 16mg twice-a-day 5-day on/2-day off dose of ASP5878 (5on-2off) is administered to participants with solid tumors and safety, PK, PD and efficacy of ASP5878 are evaluated. The expansion part starts from Cycle 1 and each cycle consists of 28 days.

Inclusion Criteria:

• Histologically or cytologically confirmed solid tumor.

• Participant must meet at least one of the following criteria in the judgment of the investigator or sub-investigator:

  • Disease progression despite standard therapies
  • Progressive disease without any standard therapies established
  • Standard therapies are considered intolerable

• Eastern Cooperative Oncology Group performance status 0 or 1.

• Predicted life expectancy ≥ 12 weeks in the judgment of the investigator or sub-investigator.

Exclusion Criteria:

• Participant with ≥ Grade 2 (CTCAE v 4.0-JCOG) persistent symptoms and objective findings due to the toxicity attributable to prior treatment with antitumor effect (except alopecia).
• Participant who received a prior treatment intended for antitumor effect (medication, surgery, radiotherapy, etc.) within 4 weeks prior to the planned first day of study drug dosing (or participant who received mitomycin C or Nitrosourea within 6 weeks prior to the planned first day of study drug dosing).
• A major surgical procedure within 4 weeks prior to the planned first day of study drug dosing or a surgical procedure is planned during the course of the study.
• Participant who were treated with other investigational drug or medical device within 4 weeks prior to the planned first day of study drug dosing.
• Participant who has a history of organ transplantation.
• Participant with a brain metastasis with symptoms or requiring treatment.