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

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.

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)