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

Metastatic Breast Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04024436
• Other study ID #: FOENIX-MBC2 TAS-120-201
• Secondary ID: 2019-001164-30
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: August 30, 2019
• Est. completion date: July 5, 2024

Study information

• Verified date: May 2024
• Source: Taiho Oncology, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 168
• Est. completion date: July 5, 2024
• Est. primary completion date: May 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Breast Neoplasms
• FGFR2 Amplification
• Metastatic Breast Cancer

Intervention

Drug:
• Futibatinib
Futibatinib 20mg once daily on a 28 day cycle
• Futibatinib plus Fulvestrant
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.

Locations

Country	Name	City	State
Canada	Tom Baker Cancer Center	Calgary
Canada	SunnyBrook Health Sciences	Toronto
France	Centre Leon Berard	Lyon
France	Institut Gustave Roussy	Villejuif	Cedex
Italy	AOU Policlinico - Vittorio Emanuele	Catania
Italy	Istituto Europeo Di Oncologia - IEO	Milano
Italy	AOU Modena Policlinico	Modena
Italy	Ospedale E. Agnelli	Pinerolo
Italy	Azienda Ospedaliero Universitaria Pisana	Pisa
Italy	Fondazione Policlinico Universitario Agostino Gemelli IRCCS	Roma
Italy	Istituto Nazionale Tumori Regina Elena	Roma
Portugal	Centro Hospitalar Universitario Lisboa Norte	Lisboa
Portugal	Instituto Portugues de Oncologia do Porto	Porto
Portugal	Porto University	Porto
Spain	Vall d'Hebron	Barcelona
Spain	START Madrid - CIOCC	Madrid
Spain	University Gregorio Marañon	Madrid
United Kingdom	HCA Healthcare UK	London	England
United Kingdom	The Christie NHS Foundation Trust	Manchester	England
United Kingdom	The Royal Marsden NHS Foundation Trust	Sutton	England
United States	BIDMC	Boston	Massachusetts
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Tennessee Oncology	Chattanooga	Tennessee
United States	UT Southwestern	Dallas	Texas
United States	Florida Cancer Specialists	Fort Myers	Florida
United States	MD Anderson	Houston	Texas
United States	Mayo Clinic - FL	Jacksonville	Florida
United States	HCA Midwest Health	Kansas City	Missouri
United States	Tennessee Oncology	Nashville	Tennessee
United States	Mayo Clinic - AZ	Phoenix	Arizona
United States	Mayo Clinic - MN	Rochester	Minnesota
United States	Florida Cancer Specialists	Saint Petersburg	Florida
United States	USCF	San Francisco	California
United States	Florida Cancer Specialists	Tallahassee	Florida
United States	Moffitt Cancer Center	Tampa	Florida
United States	Florida Cancer Specialists	West Palm Beach	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Taiho Oncology, Inc.

Countries where clinical trial is conducted

United States,  Canada,  France,  Italy,  Portugal,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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)
Primary	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	Complete Response (CR) - Cohort 3	CR is defined as the disappearance of all target and/or non-target lesions	12 months (estimated)
Secondary	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)
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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