Patient case: 57-year-old male with lung cancer; genetic feature: FGFR1

Clinical trial: A Dose Finding Study Followed by a Safety and Efficacy Study in Patients With Advanced Solid Tumors or Multiple Myeloma With FGF/FGFR-Related Abnormalities

Summary: The purpose of this study is to determine the safety of TAS-120 and determine the most appropriate dose for the subsequent phase 2 safety and efficacy study in patients with advanced solid tumors and multiple myeloma with genetic abnormalities.
  The progression of cancers is caused by a complex series of multiple genetic and molecular events leading to changes in the patients DNA. The fibroblast growth factor/fibroblast growth factor receptor (FGF/FGFR) signaling pathway is important for normal organ, vascular and skeletal development. However, FGFR gene abnormalities have been linked to various cancers.
  TAS-120 is a highly potent, selective small molecule inhibitor of FGFR and is therefore is being studied as a therapy for cancer.

Detailed description: Background and rationale for study:
  -  Activating fibroblast growth factor receptor (FGFR) gene abnormalities are reported in various cancers including non-small cell lung cancer (NSCLC) (FGFR1 amplification), breast (FGFR1 and 2 amplification), gastric (FGFR2 amplification), bladder (FGFR3 activating mutation or gene translocation), endometrial (FGFR2 activating mutation), multiple myeloma (FGFR3 gene translocation), and rhabdomyosarcoma (FGFR4-activating mutation).
  -  TAS-120 is a novel, highly potent and selective small molecule FGFR inhibitor.
  Phase 1 Dose Escalation:
  Primary
  • To investigate the safety and to determine the maximum tolerated dose (MTD) and the recommended Phase 2 dose (RP2D) of TAS-120 in patients with advanced solid tumors with or without FGF/FGFR abnormalities for whom no available therapy is likely to convey clinical benefit.
  Secondary
  -  To investigate the clinical pharmacokinetics (PK) of TAS-120.
  -  To investigate the clinical pharmacodynamics of TAS-120.
  -  To determine any preliminary antitumor activity observed with TAS-120.
  Phase 1 Expansion and Phase 2:
  Primary •To investigate the efficacy of the TAS-120 RP2D in patients with advanced solid tumors or multiple myeloma, with FGF/FGFR abnormalities for whom no available therapy is likely to convey clinical benefit.
  Secondary
  •To investigate the safety of TAS-120.

Eligibility: Inclusion Criteria:
  Provide written informed consent.
  Is ≥18 years of age.
  Patients with confirmed advanced metastatic solid tumor(s) with or without abnormalities of FGF/FGFR who have failed all standard therapies or for whom standard therapy does not exist.
  Patients with confirmed multiple myeloma with amplification, mutation or translocation or other associated abnormalities of FGF/FGFR who have failed all standard therapies or for whom standard therapy does not exist.
  Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
  Women of child-bearing potential must have a negative pregnancy test
  Exclusion Criteria:
  History of endocrine alteration of calcium-phosphorus homeostasis.
  History of ectopic mineralization/calcification
  Current evidence of corneal disorder/keratopathy
  History or current evidence of cardiac arrhythmia and/or conduction abnormality.
  QTc > 470 msec on ECG conducted during Screening period
  Treatment with any of the following within the specified time frame prior to the first dose of TAS-120:
  1. Major surgery within the previous 4 weeks
  2. Radiotherapy for extended field within 4 weeks
  3. Any noninvestigational anticancer therapy within 3 weeks
  4. Any medication administered within 7 days prior to first dose of TAS-120 that is known to affect QT interval
  5. Any investigational agent received either concurrently or within the previous 30 days.
  A serious illness or medical condition(s)
  Known hypersensitivity to TAS-120 or any drugs similar to it in structure or class.
  Pregnant or lactating female.

Relevance to patient case: not relevant