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
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
64
Futibatinib 20mg once daily on a 28-day cycle
Futibatinib 20mg once daily on a 28-day cycle and fulvestrant 500 mg 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.
Mayo Clinic - AZ
Phoenix, Arizona, United States
USCF
San Francisco, California, United States
Florida Cancer Specialists
Fort Myers, Florida, United States
Mayo Clinic - FL
Jacksonville, Florida, United States
Florida Cancer Specialists
St. Petersburg, Florida, United States
Florida Cancer Specialists
Objective Response Rate (ORR) - Cohorts 1, 2
ORR was defined as the percentage of participants with a confirmed response of either complete response (CR) or partial response (PR), based on Investigator assessment. CR was defined as disappearance of all target lesions. Any pathological lymph node must have reduction in short axis to \<10 millimeters (mm). PR was defined as at least a 30% decrease in the sum of diameters of the target lesions, taking as a reference the baseline sum diameters. ORR was calculated based on the best overall response recorded from the start of treatment until progressive disease or start of subsequent new anticancer treatment. Percentages were rounded off to the nearest single decimal place.
Time frame: At the end of every 2 cycles until disease progression (up to 40 months)
Clinical Benefit Rate (CBR) - Cohort 3
CBR was defined as the percentage of participants with a confirmed response of CR or stable disease (SD) lasting at least 24 weeks, based on Investigator assessment. CR was defined as disappearance of all target lesions. Any pathological lymph node must have reduction in short axis to \<10mm. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), referencing the smallest sum diameters while on study. PR was defined as at least a 30% decrease in the sum of diameters of the target lesions, taking as a reference the baseline sum diameters. PD was defined as at least a 20% increase in the sum of diameters of the target lesions, taking as a reference the smallest sum on study, including the baseline sum. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Definitive new lesion presence also indicates progression. Percentages were rounded off to the nearest
Time frame: At the end of every 2 cycles until disease progression (up to 40 months)
6-month Progression-free Survival (PFS) Rate - Cohort 4
The 6-month PFS rate was defined as the percentage of participants who are alive and progression-free 6 months after the first dose of study drug. Percentages were rounded off to the nearest single decimal place.
Time frame: At the end of every 2 cycles until disease progression (up to 6 months)
Complete Response (CR) Rate - Cohort 3
CR rate was defined as the percentage of participants who achieved CR. CR was defined as disappearance of all targets. Any pathological lymph node must have reduction in short axis to \<10 mm. Percentages were rounded off to the nearest single decimal place.
Time frame: At the end of every 2 cycles until disease progression (up to 40 months)
Overall Response Rate (ORR) - Cohort 4
ORR was defined as the percentage of participants with a confirmed response of either CR or PR, based on Investigator assessment. CR was defined as disappearance of all target lesions. Any pathological lymph node must have reduction in short axis to \<10 mm. PR was defined as at least a 30% decrease in the sum of diameters of the target lesions, taking as a reference the baseline sum diameters. ORR was calculated based on the best overall response recorded from the start of treatment until progressive disease or start of subsequent new anticancer treatment. Percentages were rounded off to the nearest single decimal place.
Time frame: At the end of every 2 cycles until disease progression (up to 40 months)
Clinical Benefit Rate (CBR) - Cohort 1,2, and 4
CBR was defined as the percentage of participants with a confirmed response of CR, PR or SD lasting at least 24 weeks, based on Investigator assessment. CR was defined as disappearance of all target lesions. Any pathological lymph node must have reduction in short axis to \<10 mm. PR was defined as at least a 30% decrease in the sum of diameters of the target lesions, taking as a reference the baseline sum diameters. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, referencing the smallest sum diameters while on study. PD was defined as at least a 20% increase in the sum of diameters of the target lesions, taking as a reference the smallest sum on study, including the baseline sum. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Definitive new lesion presence also indicates progression. Percentages were rounded off to the nearest single decimal place.
Time frame: At the end of every 2 cycles until disease progression (up to 40 months)
6-month PFS Rate - Cohorts 1,2, and 3
The 6-month PFS rate was defined as the percentage of participants who are alive and progression-free 6 months after the first dose of study drug. Percentages were rounded off to the nearest single decimal place.
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Tallahassee, Florida, United States
Moffitt Cancer Center
Tampa, Florida, United States
Florida Cancer Specialists
West Palm Beach, Florida, United States
Massachusetts General Hospital
Boston, Massachusetts, United States
BIDMC
Boston, Massachusetts, United States
...and 27 more locations
Time frame: At the end of every 2 cycles until disease progression (up to 6 months)
Progression Free Survival (PFS)
PFS was defined as the time from the first dose of study therapy to the date of death (any cause) or disease progression based on investigator assessment, whichever occurs first. The PFS was analyzed using a Kaplan-Meier method with PFS time being censored on the date of the last disease assessment. The 95% CI for median PFS was provided using the Kaplan-Meier procedure.
Time frame: At the end of every 2 cycles until disease progression (up to 40 months)
Duration of Response (DOR)
DOR was defined as the time from the first documentation of objective response to the to the date of death (any cause) or disease progression, based on Investigator assessment, whichever occurs first. Objective response was defined as participants with a confirmed response of either CR or PR, based on Investigator assessment. CR was defined as disappearance of all target lesions. Any pathological lymph node must have reduction in short axis to \<10 mm. PR was defined as at least a 30% decrease in the sum of diameters of the target lesions, taking as a reference the baseline sum diameters. DOR was estimated using the Kaplan-Meier method.
Time frame: At the end of every 2 cycles until disease progression (up to 40 months)
Overall Survival (OS)
OS was defined as the time (in months) from the date of first dose of the study drug to the date of death. Participants without a documented death date were censored on the last date they were known to be alive. The OS was presented using a Kaplan-Meier estimate. The 95% CI for median OS was provided using the Kaplan-Meier procedure.
Time frame: Up to 40 months
Number of Participants With Adverse Events (AEs)
An AE is defined as any untoward medical occurrence in a clinical study participant and does not necessarily have a causal relationship with the study drug.
Time frame: From the first dose of study drug up to 30 days after the last dose (Up to 40 months)
Number of Participants With Dose Limiting Toxicities (DLTs) - Cohort 4
A DLT was defined as any AE that occurs during Cycle 1 that is not clearly attributable to an extraneous cause, such as an underlying disease, occurring in Cycle 1, and meeting at least one of the criteria defined in the protocol. An AE is defined as any untoward medical occurrence in a clinical study participant and does not necessarily have a causal relationship with the study drug.
Time frame: Cycle 1 (cycle length= 28 days)