Patient case: 64-year-old male with bladder cancer; genetic feature: FGFR3 (S249C)

Clinical trial: A Study of TAS-120 in Patients With Advanced Solid Tumors

Summary: This is an open-label, nonrandomized, Phase 1 dose-escalation, dose-expansion, and Phase 2 study targeting tumors with FGF/FGFR aberrations. The purpose of the study is to evaluate the safety, tolerability, PK, pharmacodynamic, and anti-tumor activity of TAS-120 in patients with advanced solid tumors with and without FGF/FGFR-related abnormalities.
  The study will be conducted in 3 parts, (1) Dose escalation to determine the MTD and/ or RP2D of TAS-120 in which this part of the study has been completed; (2) Phase 1 expansion to further evaluate the safety and efficacy of RP2D of TAS-120 in patients with tumors harboring specific FGFR aberrations, specifically in patients with cholangiocarcinoma, gliomas , urothelial carcinomas and any other tumors with FGFR fusion or activating mutation or amplification. Up to approximately 185 patients will be enrolled in the phase 1 expansion; and (3) Phase 2 study to confirm ORR of TAS-120 in intra-hepatic CCA patients with tumors harboring FGFR2 gene fusions. Approx. 100 patients will be enrolled in phase 2.

Detailed description: Phase 1 Dose Escalation Phase 1 Dose Escalation has been completed as of Dec 2017
  Phase 1 Dose Expansion:
  Up to approximately 185 patients will be enrolled among the 8 groups as outlined below:
  -  Group 1- CCA (iCCA or eCCA) with FGFR2 gene fusions.
  -  Group 2- CCA (iCCA or eCCA) with FGFR2 gene fusions that are chemotherapy naive or intolerant to first line chemotherapy (i.e., on chemotherapy regimen ≤ 1 cycle).
  -  Group 3 - CCA (iCCA or eCCA) with FGFR2 gene fusions treated with prior FGFR inhibitors.
  -  Group 4 - CCA (iCCA or eCCA) with other FGFR2 abnormalities, ie, gene mutations, rearrangements or amplifications.
  -  Group 5 - GBM or grade III glioma (i.e, anaplastic astrocytoma or anaplastic oliogodendroglioma) with FGFR gene fusions or activating mutations
  -  Group 6 - Advanced urothelial carcinoma with FGFR3 fusions or FGFR3 activating mutations.
  -  Group 7: Basket of tumor types with tumors harboring FGFR2 amplification (≥10 copies).
  -  Group 8 - Basket of tumor types (except CCA, brain tumors and advanced urothelial carcinomas) with tumors harboring FGFR gene fusions or activating mutations.
  Phase 2:
  Approximately 100 iCCA patients with confirmed FGFR2 gene fusions will be treated. Patients will be centrally screened for FGFR2 gene fusions. This is a Single arm study with the primary endpoint of ORR.

Eligibility: Inclusion Criteria:
  Has histologically or cytologically confirmed, locally advanced, metastatic cancer meeting the following criteria:
  Phase 1 Expansion
  1. Patient has failed all standard therapies or standard therapy does not exist or is not tolerated.
  2. Patient has specific FGF/FGFR aberrations
  -  Intrahepatic or extrahepatic cholangiocarcinoma with FGFR2 gene fusions or other FGFR2 abnormalities, i.e., gene mutations (see Appendix A), rearrangements or amplifications
  -  Glioblastoma or grade III glioma (i.e., anaplastic astrocytoma or anaplastic oligodendroglioma) with FGFR gene fusions or activating mutations.
  -  Advanced urothelial carcinoma with FGFR3 fusions or FGFR3 activating mutations
  -  All other tumor types harboring FGF9, FGF19 or FGFR2 amplifications (≥ 10 copies), FGFR gene fusions, or FGFR activating mutations
  Phase 2
  1. Patient has histologically or cytologically confirmed, locally advanced, metastatic, unresectable iCCA harboring FGFR2 gene fusions based on results from a NGS assay by the Sponsor's designated central laboratory
  2. Patient has been treated with and failed at least one prior systemic gemcitabine and platinum-based chemotherapy for the advanced disease
  3. Must have documentation of radiographic progression of disease on prior systemic therapy
  4. Patient has measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) guidelines (version 1.1, 2009) for advanced solid tumors or RANO criteria (2010) for brain tumors.
  5. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
  6. Adequate organ function
  Exclusion Criteria:
  A patient will be excluded from this study if any of the following criteria are met:
  1. History and/or current evidence of non-tumor related alteration of calcium-phosphorus homeostasis.
  2. History and/or current evidence of clinically significant ectopic mineralization/calcification.
  3. History and/or current evidence of clinically significant retinal disorder confirmed by retinal examination.
  4. A serious illness or medical condition(s)

Relevance to patient case: possibly relevant