A Phase 2 Study of Futibatinib in Patients With Specific FGFR Aberrations
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 115
- 试验地点
- 61
- 主要终点
- Objective Response Rate (ORR) Based on Independent Central Review (IRC) in Cohorts A and B
研究概览
简要总结
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.
详细描述
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).
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
- •Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
- •Known FGFR aberration status and tumor type that meet all of the criteria for 1 of the following cohorts:
- •a. Cohort A
- •i. Histologically-confirmed, locally-advanced, advanced, or metastatic solid tumors harboring a FGFR1-4
- •ii. Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
- •iii. Had disease progression/recurrence after standard treatment for their cancer
- •b. Cohort B
- •i. Histologically-confirmed, locally-advanced, advanced, or metastatic gastric or gastroesophageal junction cancer harboring a FGFR2 amplification.
- •ii. Measurable disease per RECIST 1.1
- •iii. Received at least 2 prior systemic regimens for advanced/metastatic disease
- •iv. Experienced disease progression/recurrence during or after the most recent prior systemic treatment for advanced/metastatic gastric cancer or GEJ cancer
- •c. Cohort C
- •i. Confirmed myeloid or lymphoid neoplasms as defined by WHO criteria with a FGFR1 rearrangement
- •ii. Not a candidate for hematological stem cell transplant (HSCT) or relapsed after HSCT and donor lymphocyte infusion, and progressed and not a candidate for other therapies
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 in the opinion of the Investigator
- •Ectopic mineralization/calcification including, but not limited to, soft tissue, kidneys, intestine, or myocardia and lung, considered clinically significant in the opinion of the Investigator
- •Retinal or corneal disorder confirmed by retinal/corneal examination and considered clinically significant in the opinion of the Investigator.
- •Prior treatment with an FGFR inhibitor
- •Brain metastases that are untreated or clinically or radiologically unstable (that is, have been stable for <1 month)
研究组 & 干预措施
Futibatinib (Cohort A)
Participants with advanced or metastatic solid tumors harboring FGFR1-4 rearrangements received futibatinib 20 mg, oral tablets, once a day on a continuous 28-day cycle up to a maximum of 841 days.
干预措施: Futibatinib (Drug)
Futibatinib (Cohort B)
Participants with advanced or metastatic solid gastric or GEJ cancer harboring FGFR2 amplification received futibatinib 20 mg, oral tablets, once a day on a continuous 28-day cycle up to a maximum of 297 days.
干预措施: Futibatinib (Drug)
Futibatinib (Cohort C)
Participants with myeloid or lymphoid neoplasm harboring FGFR1 rearrangement were to receive futibatinib 20 mg, oral tablets, once a day on a continuous 28-day cycle until disease progression, unacceptable toxicity or other treatment discontinuation criteria are met.
干预措施: Futibatinib (Drug)
结局指标
主要结局
Objective Response Rate (ORR) Based on Independent Central Review (IRC) in Cohorts A and B
时间窗: At the end of every 2 cycles until disease progression (Up to 31 months)
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.
Complete Response (CR) Rate in Cohort C
时间窗: At the end of every 2 cycles until disease progression (Up to 31 months)
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.
次要结局
- ORR Based on Investigator Assessment in Cohorts A and B(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(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(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(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(At the end of every 2 cycles until disease progression (Up to 31 months))
- Overall Survival (OS) in Cohorts A, B and C(Up to 31 months)
- Disease Control Rate (DCR) Based on IRC in Cohort A and B(At the end of every 2 cycles until disease progression (Up to 31 months))
- DCR Based on Investigator Review in Cohort A and B(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(Up to 31 months)
- Duration of CR in Cohort C(Up to 31 months)
- Duration of CR+CRi in Cohort C(Up to 31 months)
- Complete Cytogenetic Response (CCyR) Rate in Cohort C(Up to 31 months)
- Partial Cytogenetic Response (PCyR) Rate in Cohort C(Up to 31 months)
- Relapse-free Survival (RFS) in Cohort C(Up to 31 months)
- Event-free Survival (EFS) in Cohort C(Up to 31 months)
- Number of Participants With Treatment Emergent Adverse Events (TEAEs) - Cohort A, B and C(From the first dose of study drug up to 30 days after the last dose (Up to 31 months))