Clinical trial NCT04024436: A Study of TAS-120 in Patients With Metastatic Breast Cancer
Official title: A Phase 2 Study of TAS-120 in Metastatic Breast Cancers Harboring Fibroblast Growth Factor Receptor (FGFR) Amplifications
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Metastatic Breast Cancer
FGFR 1 High Amplification
FGFR2 Amplification
Keywords: Futibatinib
Metastatic Breast Cancer
FGFR
TAS-120
Lead sponsor: Taiho Oncology, Inc.
Sponsor class: INDUSTRY
First posted: 2019-07-18
Enrollment: 168
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed 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

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

Primary outcomes:
measure: Objective Response Rate (ORR) - Cohorts 1, 2
timeFrame: 12 months (estimated)
measure: Clinical Benefit Rate (CBR) - Cohort 3
timeFrame: 12 months (estimated)
measure: 6-month Progression-free Survival (PFS) rate - Cohort 4
timeFrame: 12 months (estimated)
Secondary outcomes:
measure: Complete Response (CR) - Cohort 3
timeFrame: 12 months (estimated)
measure: Overall Response Rate (ORR) - Cohort 4
timeFrame: 12 months (estimated)
measure: Clinical Benefit Rate (CBR) - Cohort 1,2, and 4
timeFrame: 12 months
measure: 6-month Progression-free Survival (PFS) rate - Cohorts 1-3
timeFrame: 12 months
measure: Progression-free Survival (PFS)
timeFrame: 12 months
measure: Duration of Response (DOR)
timeFrame: 12 months
measure: Overall Survival (OS)
timeFrame: 12 months
measure: Number of Adverse Events (AEs) Related to TAS-120 as a monotherapy and in combination with Fulvestrant
timeFrame: 12 months
measure: Number of Adverse Events (AEs) Related to Futibatinib as a monotherapy and in combination with Fulvestrant
timeFrame: 12 months
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Mayo Clinic - AZ
state: Arizona
city: San Francisco
country: United States
facility: USCF
state: California
city: Fort Myers
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Jacksonville
country: United States
facility: Mayo Clinic - FL
state: Florida
city: Saint Petersburg
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Tallahassee
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: West Palm Beach
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: BIDMC
state: Massachusetts
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Rochester
country: United States
facility: Mayo Clinic - MN
state: Minnesota
city: Kansas City
country: United States
facility: HCA Midwest Health
state: Missouri
city: Chattanooga
country: United States
facility: Tennessee Oncology
state: Tennessee
city: Nashville
country: United States
facility: Tennessee Oncology
state: Tennessee
city: Dallas
country: United States
facility: UT Southwestern
state: Texas
city: Houston
country: United States
facility: MD Anderson
state: Texas
city: Calgary
country: Canada
facility: Tom Baker Cancer Center
city: Toronto
country: Canada
facility: SunnyBrook Health Sciences
city: Villejuif
country: France
facility: Institut Gustave Roussy
state: Cedex
city: Lyon
country: France
facility: Centre Leon Berard
city: Catania
country: Italy
facility: AOU Policlinico - Vittorio Emanuele
city: Milano
country: Italy
facility: Istituto Europeo Di Oncologia - IEO
city: Modena
country: Italy
facility: AOU Modena Policlinico
city: Pinerolo
country: Italy
facility: Ospedale E. Agnelli
city: Pisa
country: Italy
facility: Azienda Ospedaliero Universitaria Pisana
city: Roma
country: Italy
facility: Istituto Nazionale Tumori Regina Elena
city: Roma
country: Italy
facility: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
city: Lisboa
country: Portugal
facility: Centro Hospitalar Universitario Lisboa Norte
city: Porto
country: Portugal
facility: Porto University
city: Porto
country: Portugal
facility: Instituto Portugues de Oncologia do Porto
city: Barcelona
country: Spain
facility: Vall d'Hebron
city: Madrid
country: Spain
facility: University Gregorio Marañon
city: Madrid
country: Spain
facility: START Madrid - CIOCC
city: London
country: United Kingdom
facility: HCA Healthcare UK
state: England
city: Manchester
country: United Kingdom
facility: The Christie NHS Foundation Trust
state: England
city: Sutton
country: United Kingdom
facility: The Royal Marsden NHS Foundation Trust
state: England
Study officials:
References: