FGFR 1 High Amplification, FGFR2 Amplification, Metastatic Breast Cancer
Conditions
Keywords
Futibatinib, Metastatic Breast Cancer, FGFR, TAS-120
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
Interventions
DRUGFutibatinib
Futibatinib 20mg once daily on a 28-day cycle
DRUGFutibatinib plus Fulvestrant
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.
Sponsors
Taiho Oncology, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) - Cohorts 1, 2 | At the end of every 2 cycles until disease progression (up to 40 months) | 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. |
| Clinical Benefit Rate (CBR) - Cohort 3 | At the end of every 2 cycles until disease progression (up to 40 months) | 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 |
| 6-month Progression-free Survival (PFS) Rate - Cohort 4 | At the end of every 2 cycles until disease progression (up to 6 months) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 6-month PFS Rate - Cohorts 1,2, and 3 | At the end of every 2 cycles until disease progression (up to 6 months) | 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. |
| Progression Free Survival (PFS) | At the end of every 2 cycles until disease progression (up to 40 months) | 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. |
| Duration of Response (DOR) | At the end of every 2 cycles until disease progression (up to 40 months) | 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. |
| Complete Response (CR) Rate - Cohort 3 | At the end of every 2 cycles until disease progression (up to 40 months) | 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. |
| Number of Participants With Adverse Events (AEs) | From the first dose of study drug up to 30 days after the last dose (Up to 40 months) | 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. |
| Number of Participants With Dose Limiting Toxicities (DLTs) - Cohort 4 | Cycle 1 (cycle length= 28 days) | 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. |
| Overall Survival (OS) | Up to 40 months | 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. |
| Overall Response Rate (ORR) - Cohort 4 | At the end of every 2 cycles until disease progression (up to 40 months) | 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. |
| Clinical Benefit Rate (CBR) - Cohort 1,2, and 4 | At the end of every 2 cycles until disease progression (up to 40 months) | 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. |
Countries
Canada, France, Italy, Portugal, Spain, United Kingdom, United States
Participant flow
Recruitment details
Participants took part in the study from 28 January 2020 to 06 September 2023.
Pre-assignment details
A total of 64 participants were enrolled in either Cohorts 1, 2 or 3 to receive futibatinib or to Cohort 4 to receive futibatinib plus fulvestrant.
Participants by arm
| Arm | Count |
|---|---|
| Futibatinib (Cohort 1) Participants with advanced or metastatic HR+, HER2- breast cancer, harboring FGFR2 gene amplification, with measurable disease received futibatinib, 20 mg, oral tablets, once daily for a continuous 28-day cycle up to maximum of 244 days | 17 |
| Futibatinib (Cohort 2) Participants with advanced or metastatic TNBC, harboring FGFR2 gene amplification, with measurable disease received futibatinib, 20 mg, oral tablets, once daily for a continuous 28-day cycle up to maximum of 1066 days. | 21 |
| Futibatinib (Cohort 3) Participants with advanced or metastatic HR+, HER2- or TNBC, harboring FGFR2 gene amplification, with non-measurable disease received futibatinib, 20 mg, oral tablets, once daily for a continuous 28-day cycle up to maximum of 252 days. | 4 |
| Futibatinib Plus Fulvestrant (Cohort 4) Participants with advanced or metastatic HR+ HER2- breast cancer, harboring FGFR1 gene amplification, with measurable disease, received futibatinib, 20 mg, oral tablets, once daily for a continuous 28-day cycle up to maximum of 645 days. They also received IM fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and Day 1 of every subsequent cycle up to maximum of 618 days. | 22 |
| Total | 64 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Death | 10 | 14 | 2 | 7 |
| Overall Study | Loss to follow up | 1 | 0 | 0 | 1 |
| Overall Study | Reason Not Specified | 0 | 1 | 0 | 2 |
| Overall Study | Study termination by sponsor | 4 | 6 | 2 | 11 |
| Overall Study | Withdrawal of consent | 2 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Futibatinib (Cohort 1) | Futibatinib (Cohort 2) | Futibatinib (Cohort 3) | Futibatinib Plus Fulvestrant (Cohort 4) | Total |
|---|---|---|---|---|---|
| Age, Continuous | 59.8 years STANDARD_DEVIATION 11.42 | 51.4 years STANDARD_DEVIATION 14.5 | 60.8 years STANDARD_DEVIATION 5.74 | 52.7 years STANDARD_DEVIATION 12.68 | 54.7 years STANDARD_DEVIATION 13.01 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 1 Participants | 0 Participants | 2 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 15 Participants | 15 Participants | 4 Participants | 13 Participants | 47 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 5 Participants | 0 Participants | 7 Participants | 13 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 1 Participants | 0 Participants | 1 Participants | 4 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 7 Participants | 0 Participants | 4 Participants | 11 Participants |
| Race (NIH/OMB) White | 14 Participants | 12 Participants | 4 Participants | 16 Participants | 46 Participants |
| Sex: Female, Male Female | 17 Participants | 21 Participants | 4 Participants | 22 Participants | 64 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 10 / 17 | 14 / 21 | 2 / 4 | 7 / 22 |
| other Total, other adverse events | 16 / 17 | 21 / 21 | 4 / 4 | 22 / 22 |
| serious Total, serious adverse events | 4 / 17 | 5 / 21 | 1 / 4 | 4 / 22 |
Outcome results
Primary
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)
Population: All treated population included all enrolled participants who received at least 1 dose of study drug. This outcome measure was planned to be reported for only Cohort 4 as pre-specified in Protocol and SAP.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Futibatinib (Cohort 1) | 6-month Progression-free Survival (PFS) Rate - Cohort 4 | 45.5 percentage of participants |
Primary
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)
Population: All treated population included all enrolled participants who received at least 1 dose of study drug. This outcome measure was planned to be reported for only Cohort 3 as pre-specified in Protocol and SAP.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Futibatinib (Cohort 1) | Clinical Benefit Rate (CBR) - Cohort 3 | 50.0 percentage of participants |
Primary
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)
Population: All treated population included all enrolled participants who received at least 1 dose of study drug. This outcome measure was planned to be reported for only Cohort 1 and 2 as pre-specified in Protocol and SAP.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Futibatinib (Cohort 1) | Objective Response Rate (ORR) - Cohorts 1, 2 | 0 percentage of participants |
| Futibatinib (Cohort 2) | Objective Response Rate (ORR) - Cohorts 1, 2 | 9.5 percentage of participants |
Secondary
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.
Time frame: At the end of every 2 cycles until disease progression (up to 6 months)
Population: All treated population included all enrolled participants who received at least 1 dose of study drug. This outcome measure was planned to be reported for only Cohorts 1, 2 and 3 as pre-specified in Protocol and SAP.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Futibatinib (Cohort 1) | 6-month PFS Rate - Cohorts 1,2, and 3 | 5.9 percentage of participants |
| Futibatinib (Cohort 2) | 6-month PFS Rate - Cohorts 1,2, and 3 | 19.0 percentage of participants |
| Futibatinib Plus Fulvestrant (Cohort 4) | 6-month PFS Rate - Cohorts 1,2, and 3 | 50.0 percentage of participants |
Secondary
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)
Population: All treated population included all enrolled participants who received at least 1 dose of study drug. This outcome measure was planned to be reported for only Cohorts 1, 2 and 4 as pre-specified in Protocol and SAP.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Futibatinib (Cohort 1) | Clinical Benefit Rate (CBR) - Cohort 1,2, and 4 | 11.8 percentage of participants |
| Futibatinib (Cohort 2) | Clinical Benefit Rate (CBR) - Cohort 1,2, and 4 | 23.8 percentage of participants |
| Futibatinib Plus Fulvestrant (Cohort 4) | Clinical Benefit Rate (CBR) - Cohort 1,2, and 4 | 50.0 percentage of participants |
Secondary
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)
Population: All treated population included all enrolled participants who received at least 1 dose of study drug. This outcome measure was planned to be reported for only Cohort 3 as pre-specified in Protocol and SAP.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Futibatinib (Cohort 1) | Complete Response (CR) Rate - Cohort 3 | 0 percentage of participants |
Secondary
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)
Population: All treated population included all enrolled participants who received at least 1 dose of study drug. Overall number of participants analyzed is the number of participants with data available for analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Futibatinib (Cohort 2) | Duration of Response (DOR) | 3.38 months |
| Futibatinib Plus Fulvestrant (Cohort 4) | Duration of Response (DOR) | 6.34 months |
Secondary
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)
Population: All treated population included all enrolled participants who received at least 1 dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Futibatinib (Cohort 1) | Number of Participants With Adverse Events (AEs) | 17 Participants |
| Futibatinib (Cohort 2) | Number of Participants With Adverse Events (AEs) | 21 Participants |
| Futibatinib Plus Fulvestrant (Cohort 4) | Number of Participants With Adverse Events (AEs) | 4 Participants |
| Futibatinib Plus Fulvestrant (Cohort 4) | Number of Participants With Adverse Events (AEs) | 22 Participants |
Secondary
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)
Population: All treated population included all enrolled participants who received at least 1 dose of study drug. This outcome measure was planned to be reported for only Cohort 4 as pre-specified in Protocol and SAP.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Futibatinib (Cohort 1) | Number of Participants With Dose Limiting Toxicities (DLTs) - Cohort 4 | 0 Participants |
Secondary
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)
Population: All treated population included all enrolled participants who received at least 1 dose of study drug. This outcome measure was planned to be reported for only Cohort 4 as pre-specified in Protocol and SAP.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Futibatinib (Cohort 1) | Overall Response Rate (ORR) - Cohort 4 | 18.2 percentage of participants |
Secondary
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
Population: All treated population included all enrolled participants who received at least 1 dose of study drug.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Futibatinib (Cohort 1) | Overall Survival (OS) | 16.5 months |
| Futibatinib (Cohort 2) | Overall Survival (OS) | 10.2 months |
| Futibatinib Plus Fulvestrant (Cohort 4) | Overall Survival (OS) | 30.4 months |
| Futibatinib Plus Fulvestrant (Cohort 4) | Overall Survival (OS) | 23.9 months |
Secondary
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)
Population: All treated population included all enrolled participants who received at least 1 dose of study drug.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Futibatinib (Cohort 1) | Progression Free Survival (PFS) | 3.7 months |
| Futibatinib (Cohort 2) | Progression Free Survival (PFS) | 1.9 months |
| Futibatinib Plus Fulvestrant (Cohort 4) | Progression Free Survival (PFS) | 12.4 months |
| Futibatinib Plus Fulvestrant (Cohort 4) | Progression Free Survival (PFS) | 7.2 months |