A Phase 2 Study of TAS-120 in Metastatic Breast Cancers Harboring Fibroblast Growth Factor Receptor (FGFR) Amplifications
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 64
- 试验地点
- 33
- 主要终点
- Objective Response Rate (ORR) - Cohorts 1, 2
研究概览
简要总结
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.
详细描述
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
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Provide written informed consent
- •Age ≥ 18 years of age
- •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.
- •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
- •Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
- •Archival or (preferably) fresh tumor tissue must be available
- •Adequate organ function
排除标准
- •History and/or current evidence of any of the following disorders:
- •Non-tumor related alteration of the calcium-phosphorus homeostasis that is considered clinically significant
- •Ectopic mineralization/calcification, including but not limited to soft tissue, kidneys, intestine, or myocardia and lung, considered clinically significant
- •Retinal or corneal disorder confirmed by retinal/corneal examination and considered clinically significant
- •Prior treatment with an FGFR inhibitor
- •A serious illness or medical condition(s)
- •Brain metastases that are untreated or clinically or radiologically unstable
- •Pregnant or lactating female
研究组 & 干预措施
Futibatinib (Cohort 1)
Participants with advanced or metastatic hormone receptor - positive (HR+), human epidermal growth factor receptor 2 - negative (HER2-) breast cancer, harboring fibroblast growth factor receptor 2 (FGFR2) gene amplification, with measurable disease received futibatinib, 20 milligrams (mg), oral tablets, once daily for a continuous 28-day cycle up to maximum of 244 days.
干预措施: Futibatinib (Drug)
Futibatinib (Cohort 2)
Participants with advanced or metastatic triple negative breast cancer (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.
干预措施: Futibatinib (Drug)
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.
干预措施: Futibatinib (Drug)
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 intramuscular (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.
干预措施: Futibatinib plus Fulvestrant (Drug)
结局指标
主要结局
Objective Response Rate (ORR) - Cohorts 1, 2
时间窗: 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
时间窗: 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
时间窗: 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.
次要结局
- Complete Response (CR) Rate - Cohort 3(At the end of every 2 cycles until disease progression (up to 40 months))
- Overall Response Rate (ORR) - Cohort 4(At the end of every 2 cycles until disease progression (up to 40 months))
- Clinical Benefit Rate (CBR) - Cohort 1,2, and 4(At the end of every 2 cycles until disease progression (up to 40 months))
- 6-month PFS Rate - Cohorts 1,2, and 3(At the end of every 2 cycles until disease progression (up to 6 months))
- Progression Free Survival (PFS)(At the end of every 2 cycles until disease progression (up to 40 months))
- Duration of Response (DOR)(At the end of every 2 cycles until disease progression (up to 40 months))
- Overall Survival (OS)(Up to 40 months)
- 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))
- Number of Participants With Dose Limiting Toxicities (DLTs) - Cohort 4(Cycle 1 (cycle length= 28 days))