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

Study Overview
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Brief Summary
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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.

Detailed Description
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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

Official Title
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A Phase 2 Study of TAS-120 in Metastatic Breast Cancers Harboring Fibroblast Growth Factor Receptor (FGFR) Amplifications

Conditions
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FGFR2 Amplification, Metastatic Breast Cancer, FGFR 1 High Amplification

Intervention / Treatment
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* Drug: Futibatinib
* Drug: Futibatinib plus Fulvestrant


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Provide written informed consent Age ≥ 18 years of age 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 Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 Archival or (preferably) fresh tumor tissue must be available Adequate organ function Exclusion Criteria: History and/or current evidence of any of the following disorders: Non-tumor related alteration of the calcium-phosphorus homeostasis that is considered clinically significant Ectopic mineralization/calcification, including but not limited to soft tissue, kidneys, intestine, or myocardia and lung, considered clinically significant Retinal or corneal disorder confirmed by retinal/corneal examination and considered clinically significant Prior treatment with an FGFR inhibitor A serious illness or medical condition(s) Brain metastases that are untreated or clinically or radiologically unstable Pregnant or lactating female

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Futibatinib<br>Group/Cohort 1 Description HR+ HER2- Measurable Disease w/ FGFR2 Amplification Group/Cohort 2 Description TNBC Measurable Disease w/ FGFR2 Amplification Group/Cohort 3 Description HR+ HER2- or TNBC Non-Measurable Disease w/ FGFR2 Amplification | Drug: Futibatinib<br>* Futibatinib 20mg once daily on a 28 day cycle<br>* Other names: TAS-120;|
| Experimental: Futibatinib plus Fulvestrant<br>Group/Cohort 4 Description HR+ HER2- Measurable Disease w/ FGFR1 Amplification | Drug: Futibatinib<br>* Futibatinib 20mg once daily on a 28 day cycle<br>* Other names: TAS-120;Drug: Futibatinib plus Fulvestrant<br>* Futibatinib 20mg once daily and 500 mg fulvestrant administered intramuscularly (IM) on Days 1 and 15 of Cycle 1, then on Day 1 of Cycle 2 and beyond on a 28-day cycle.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) - Cohorts 1, 2 | Response assessments will be made based on RECIST guidelines (version 1.1, 2009) for solid tumors | 12 months (estimated) | 
| Clinical Benefit Rate (CBR) - Cohort 3 | CBR is defined as the proportion of patients with a confirmed response of CR or SD lasting at least 24 weeks | 12 months (estimated) | 
| 6-month Progression-free Survival (PFS) rate - Cohort 4 | The 6-month PFS rate is defined as the proportion of patients who are alive and progression-free 6 months after the first dose of study therapy | 12 months (estimated) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete Response (CR) - Cohort 3 | CR is defined as the disappearance of all target and/or non-target lesions | 12 months (estimated) | 
| Overall Response Rate (ORR) - Cohort 4 | Response assessments will be made based on RECIST guidelines (version 1.1, 2009) for solid tumors | 12 months (estimated) | 
| Clinical Benefit Rate (CBR) - Cohort 1,2, and 4 | CBR is defined as the proportion of patient with a confirmed response of CR, PR or SD lasting at least 24 weeks | 12 months | 
| 6-month Progression-free Survival (PFS) rate - Cohorts 1-3 | 6-month PFS rate is defined as the proportion of patients who are alive and progression-free 6 months after the first dose of study therapy | 12 months | 
| Progression-free Survival (PFS) | PFS is defined as the time from the first dose of study therapy to the date of death (any cause) or disease progression | 12 months | 
| Duration of Response (DOR) | DOR is defined as the time from first documentation of objective response to the date of death (any cause) or disease progression | 12 months | 
| Overall Survival (OS) | OS is defined as the time (in months) from the first dose of study therapy to the date of death (any cause) | 12 months | 
| Number of Adverse Events (AEs) Related to TAS-120 as a monotherapy and in combination with Fulvestrant | Standard safety monitoring and grading of treatment-emergent adverse events (AEs) will be performed | 12 months | 
| Number of Adverse Events (AEs) Related to Futibatinib as a monotherapy and in combination with Fulvestrant | Standard safety monitoring and grading of treatment-emergent adverse events (AEs) will be performed using Common Terminology Criteria for Adverse Events (CTCAE - Version 5). | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Futibatinib, Metastatic Breast Cancer, FGFR, TAS-120