The purpose of this study is to evaluate the efficacy and safety of futibatinib in patients with FGFR aberrations in 3 distinct cohorts. Patients will be enrolled into one of 3 cohorts: patients with advanced, metastatic or locally-advanced solid tumors harboring FGFR1-4 rearrangements (excluding primary brain tumors and intrahepatic cholangiocarcinoma \[iCCA\]); patients with gastric or gastro-esophageal junction (GEJ) cancer harboring FGFR2 amplification; and patients with myeloid or lymphoid neoplasms with FGFR1 rearrangements.
Study TAS-120-202 is an open-label, multinational, 3-arm Phase 2 study evaluating the efficacy, safety, tolerability, PK, and pharmacodynamics of futibatinib in patients with FGFR aberrations. Eligible patients will be assigned to 1 of 3 treatment cohorts based on diagnosis and FGFR gene aberration status. Patients will receive futibatinib at an oral dose of 20 mg once a day on a continuous 28-day cycle. The study will enroll approximately: * Cohort A: 60 patients with locally advanced, advanced, or metastatic solid tumor harboring FGFR rearrangements other than primary brain tumor or iCCA; * Cohort B: 35 patients with locally-advanced, advanced, or metastatic gastric cancer or gastro-esophageal junction (GEJ) with FGFR2 amplification; * Cohort C: 20 patients with myeloid or lymphoid neoplasms (MLN) with FGFR1 rearrangements Treatment in all cohorts will continue until disease progression, unacceptable toxicity, or any other of the criteria for treatment discontinuation is met. For patients who discontinue treatment for reasons other than disease progression, tumor assessments should be continued until radiologic disease progression is documented or until initiation of subsequent new anticancer therapy (whichever occurs first). Patients will be followed for survival every 12 weeks (±2 weeks) until survival events (deaths) have been reported for 75% of enrolled patients or the study is terminated early by the Sponsor. Additional cohorts may be added in the future in case of new emerging efficacy data.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
115
Futibatinib tablets were dosed orally every day on a continuous 28-day cycle
Banner MD Anderson Cancer Center
Gilbert, Arizona, United States
UCLA Medical Center
Los Angeles, California, United States
Georgetown University - Lombardi Comprehensive Cancer Center
Washington D.C., District of Columbia, United States
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, United States
University of Maryland
Baltimore, Maryland, United States
Objective Response Rate (ORR) Based on Independent Central Review (IRC) in Cohorts A and B
ORR was defined as the percentage of participants experiencing a best overall response of partial response (PR) or complete response (CR) (per Response Evaluation Criteria in Solid Tumors, RECIST version 1.1), based on IRC of radiological images. 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 31 months)
Complete Response (CR) Rate in Cohort C
CR rate was defined as the percentage of participants who achieved a CR (per response criteria for myeloid or lymphoid neoplasm) based on investigator assessment of imaging, peripheral blood, and bone marrow. CR was defined as disappearance of all target lesions. Any pathological lymph node must have reduction in short axis to \<10 mm.
Time frame: At the end of every 2 cycles until disease progression (Up to 31 months)
ORR Based on Investigator Assessment in Cohorts A and B
ORR was defined as the percentage of participants experiencing a best overall response of PR or CR (per RECIST 1.1), 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 31 months)
Duration of Response (DOR) Based on IRC in Cohorts A, B and C
DOR was defined as the time from the first documentation of response (CR or PR in based on IRC) to the first documentation of objective tumor progression or death due to any cause, whichever occurs first. 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 31 months)
DOR Based on Investigator Assessment in Cohorts A, B and C
DOR was defined as the time from the first documentation of response (CR or PR in based on Investigator Assessment) to the first documentation of objective tumor progression or death due to any cause, whichever occurs first. 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 31 months)
Progression- Free Survival (PFS) Based on IRC in Cohorts A, B and C
PFS was defined as the time from first dose of the study therapy to the date of death (any cause) or disease progression (based on IRC), 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 31 months)
PFS Based on Investigator Review in Cohorts A, B and C
PFS was defined as the time from first dose of the study therapy to the date of death (any cause) or disease progression (based on Investigator Review), 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 31 months)
Overall Survival (OS) in Cohorts A, B and C
OS was defined as the time from the date of first dose to the death date. 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 31 months
Disease Control Rate (DCR) Based on IRC in Cohort A and B
DCR was defined as the percentage of participants experiencing a best overall response of stable disease (SD), PR, or CR (per RECIST 1.1), based on IRC. 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. PD was defined as at least a 20% increase in the sum of target lesion diameters from the smallest on study (including baseline), with an absolute increase of ≥ 5 mm, or the appearance of new lesions. 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. Percentages were rounded off to the nearest single decimal place.
Time frame: At the end of every 2 cycles until disease progression (Up to 31 months)
DCR Based on Investigator Review in Cohort A and B
DCR was defined as the percentage of participants experiencing a best overall response of SD, PR, or CR (per RECIST 1.1), based on IRC. 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 target lesion diameters from the smallest on study (including baseline), with an absolute increase of ≥ 5 mm, or the appearance of new lesions. 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. Percentages were rounded off to the nearest single decimal place.
Time frame: At the end of every 2 cycles until disease progression (Up to 31 months)
CR+ Complete Response With Incomplete Hematological Recovery (CRi) Rate in Cohort C
CR+CRi rate was defined as the percentage of participants who achieved a CR or CRi.
Time frame: Up to 31 months
Duration of CR in Cohort C
Duration of CR was defined as the time from the first documentation of CR to the first documentation of recurrence or death due to any cause, whichever occurs first.
Time frame: Up to 31 months
Duration of CR+CRi in Cohort C
Duration of CR+CRi was defined as the time from the first documentation of CR or CRi to the first documentation of disease relapse or death due to any cause, whichever occurs first.
Time frame: Up to 31 months
Complete Cytogenetic Response (CCyR) Rate in Cohort C
CCyR rate was defined as the percentage of participants who achieved a CCyR.
Time frame: Up to 31 months
Partial Cytogenetic Response (PCyR) Rate in Cohort C
PCyR rate was defined as the percentage of participants who achieved a PCyR.
Time frame: Up to 31 months
Relapse-free Survival (RFS) in Cohort C
RFS was defined as the time from first documentation of CR to the date of death (any cause) or disease relapse or death due to any cause, whichever occurs first.
Time frame: Up to 31 months
Event-free Survival (EFS) in Cohort C
EFS was defined as the time from first dose of study therapy to treatment failure, disease relapse after CR, or participant death due to any cause, whichever occurs first.
Time frame: Up to 31 months
Number of Participants With Treatment Emergent Adverse Events (TEAEs) - Cohort A, B and C
An adverse event (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. A treatment-emergent AE (TEAE) is defined as an AE that is starting or worsening at the time of or after the first dose of study drug administration and within 30 days after the last dose of study drug, and does not necessarily have a causal relationship to the use of the study drug.
Time frame: From the first dose of study drug up to 30 days after the last dose (Up to 31 months)
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