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

Phase 2

Completed

• Conditions: Metastatic Breast Cancer; FGFR 1 High Amplification; FGFR2 Amplification
• Interventions: Drug: Futibatinib; Drug: Futibatinib plus Fulvestrant

• Registration Number: NCT04024436
• Lead Sponsor: Taiho Oncology, Inc.

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

Study Timeline

• Study First Submitted: 2019-06-24
• Study First Submitted QC: 2019-07-17
• Study First Posted: 2019-07-18
• Study Start: 2020-01-28
• Primary Completion: 2023-05-31
• Disposition First Posted: 2024-02-23
• Disposition First Submitted: 2024-05-23
• Study Completion: 2024-10-30
• Status Verified: 2024-12
• Last Update Submitted: 2024-12-03
• Last Update Posted: 2024-12-06

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 168

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Futibatinib plus Fulvestrant	Futibatinib plus Fulvestrant	Group/Cohort 4 Description HR+ HER2- Measurable Disease w/ FGFR1 Amplification
Futibatinib plus Fulvestrant	Futibatinib	Group/Cohort 4 Description HR+ HER2- Measurable Disease w/ FGFR1 Amplification
Futibatinib	Futibatinib	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

Primary Outcome Measures

Name	Time	Method
Objective Response Rate (ORR) - Cohorts 1, 2	12 months (estimated)	Response assessments will be made based on RECIST guidelines (version 1.1, 2009) for solid tumors
Clinical Benefit Rate (CBR) - Cohort 3	12 months (estimated)	CBR is defined as the proportion of patients with a confirmed response of CR or SD lasting at least 24 weeks
6-month Progression-free Survival (PFS) rate - Cohort 4	12 months (estimated)	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

Secondary Outcome Measures

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

Trial Locations

Locations (33)

BIDMC; 🇺🇸 Boston, Massachusetts, United States

Tennessee Oncology; 🇺🇸 Nashville, Tennessee, United States

USCF; 🇺🇸 San Francisco, California, United States

Florida Cancer Specialists; 🇺🇸 West Palm Beach, Florida, United States

Mayo Clinic - FL; 🇺🇸 Jacksonville, Florida, United States

Massachusetts General Hospital; 🇺🇸 Boston, Massachusetts, United States

Dana Farber Cancer Institute; 🇺🇸 Boston, Massachusetts, United States

Tom Baker Cancer Center; 🇨🇦 Calgary, Canada

SunnyBrook Health Sciences; 🇨🇦 Toronto, Canada

AOU Policlinico - Vittorio Emanuele; 🇮🇹 Catania, Italy

Istituto Europeo Di Oncologia - IEO; 🇮🇹 Milano, Italy

AOU Modena Policlinico; 🇮🇹 Modena, Italy

Ospedale E. Agnelli; 🇮🇹 Pinerolo, Italy

Istituto Nazionale Tumori Regina Elena; 🇮🇹 Roma, Italy

Vall d'Hebron; 🇪🇸 Barcelona, Spain

The Royal Marsden NHS Foundation Trust; 🇬🇧 Sutton, England, United Kingdom

HCA Healthcare UK; 🇬🇧 London, England, United Kingdom

Mayo Clinic - AZ; 🇺🇸 Phoenix, Arizona, United States

Moffitt Cancer Center; 🇺🇸 Tampa, Florida, United States

Mayo Clinic - MN; 🇺🇸 Rochester, Minnesota, United States

HCA Midwest Health; 🇺🇸 Kansas City, Missouri, United States

UT Southwestern; 🇺🇸 Dallas, Texas, United States

MD Anderson; 🇺🇸 Houston, Texas, United States

Centre Leon Berard; 🇫🇷 Lyon, France

Institut Gustave Roussy; 🇫🇷 Villejuif, Cedex, France

Azienda Ospedaliero Universitaria Pisana; 🇮🇹 Pisa, Italy

Fondazione Policlinico Universitario Agostino Gemelli IRCCS; 🇮🇹 Roma, Italy

Porto University; 🇵🇹 Porto, Portugal

Centro Hospitalar Universitario Lisboa Norte; 🇵🇹 Lisboa, Portugal

Instituto Portugues de Oncologia do Porto; 🇵🇹 Porto, Portugal

The Christie NHS Foundation Trust; 🇬🇧 Manchester, England, United Kingdom

University Gregorio Marañon; 🇪🇸 Madrid, Spain

START Madrid - CIOCC; 🇪🇸 Madrid, Spain