A Study of TAS-120 in Patients With Metastatic Breast Cancer

The purpose of the trial is to evaluate a patient's response to a Fibroblast Growth Factor Receptor (FGFR) inhibitor, futibatinib (TAS-120), used either alone or in combination with the hormonal therapy, fulvestrant. This study will be conducted in patients with metastatic breast cancer who have specific Fibroblast Growth Factor Receptor gene abnormalities and who have previously received conventional therapies to treat their breast cancer, or who are not able to tolerate certain cancer therapies. This study will also evaluate the safety of taking futibatinib, or futibatinib and fulvestrant, by learning about the potential side effects.

This is a Phase 2, open-label, non-randomized, multicenter study designed to evaluate the efficacy and safety of futibatinib (TAS-120) and futibatinib + fulvestrant in up to 168 adult patients with locally advanced/metastatic breast cancer harboring FGFR gene amplifications. Patients will be enrolled to 1 of 4 treatment cohorts based on diagnosis and FGFR gene amplification status, and will receive either single agent futibatinib in Cohorts 1-3 or futibatinib plus fulvestrant in Cohort 4, as follows:

* Cohort 1 - HR+ HER2- Measurable Disease w/ FGFR2 Amplification
* Cohort 2 - TNBC Measurable Disease w/ FGFR2 Amplification
* Cohort 3 - HR+ HER2- or TNBC Non-Measurable Disease w/ FGFR2 Amplification
* Cohort 4 - HR+ HER2- Measurable Disease w/ FGFR1 Amplification

Eligibility Criteria:
Inclusion Criteria:

1. Provide written informed consent
2. Age ≥ 18 years of age
3. Histologically or cytologically confirmed recurrent locally advanced or metastatic breast cancer not amenable to treatment with curative intent, and the following cohort specific criteria:

   A. Cohort 1
   * HR+ HER2- breast cancer harboring an FGFR2 gene amplification.
   * Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
   * Has received 1-3 prior endocrine-containing therapies and up to 2 prior chemotherapy regimens for advanced/metastatic disease
   * Has received prior treatment with a CDK4/6 inhibitor or is ineligible for such treatment

   B. Cohort 2
   * TNBC harboring an FGFR2 gene amplification
   * Measurable disease per RECIST 1.1
   * Has received at least 1 prior chemotherapy or chemotherapy/immunotherapy (PD-L1/PD-1 inhibitors) regimen for advanced/metastatic disease

   C. Cohort 3
   * TNBC or HR+ HER2- breast cancer harboring an FGFR2 gene amplification
   * Non measurable, evaluable disease per RECIST 1.1. Patients with bone-only disease must have lytic or mixed lytic-blastic lesions
   * Other criteria for either HR+ HER2- breast cancer or TNBC should be met as described for Cohort 1 and 2, respectively

   D. Cohort 4
   * HR+ HER2- breast cancer harboring an FGFR1 high-level gene amplification
   * Measurable disease per RECIST 1.1
   * Has received 1-2 prior endocrine-containing therapies and no more than 1 prior chemotherapy regimen for advanced/metastatic disease. Prior treatment with fulvestrant is not permitted.
   * Has received prior treatment with a CDK4/6 inhibitor or is ineligible for such treatment
   * Pre/peri-menopausal patients must be on goserelin
4. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
5. Archival or (preferably) fresh tumor tissue must be available
6. Adequate organ function

Exclusion Criteria:

1. History and/or current evidence of any of the following disorders:

   1. Non-tumor related alteration of the calcium-phosphorus homeostasis that is considered clinically significant
   2. Ectopic mineralization/calcification, including but not limited to soft tissue, kidneys, intestine, or myocardia and lung, considered clinically significant
   3. Retinal or corneal disorder confirmed by retinal/corneal examination and considered clinically significant
2. Prior treatment with an FGFR inhibitor
3. A serious illness or medical condition(s)
4. Brain metastases that are untreated or clinically or radiologically unstable
5. Pregnant or lactating female