A Phase II Basket Study of the Oral Selective Pan-FGFR Inhibitor Debio 1347 in Subjects With Solid Tumors Harboring a Fusion of FGFR1, FGFR2 or FGFR3
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 63
- 试验地点
- 104
- 主要终点
- Objective Response Rate (ORR) as Centrally Measured by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) Criteria
研究概览
简要总结
The primary objective of this study is to assess the efficacy of Debio 1347 in terms of objective response rate (ORR) in participants with solid tumors harboring fibroblast growth factor receptor (FGFR)1-3 gene fusion/rearrangement.
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
- •Cytologically or histologically confirmed advanced solid tumor
- •Radiographic progression on prior systemic therapy; prior localized therapy (i.e., radiation, ablation, embolization) is allowed provided radiographic progression out-of-field or in the treatment, field is shown
- •Locally-advanced (unresectable) or metastatic disease harboring an FGFR1-3 gene fusion/rearrangement potentially leading to a functional FGFR aberrant protein, identified through local and/or central molecular assay
排除标准
- •History of hypersensitivity to any of the excipients in the Debio 1347 formulation
- •History and/or current evidence of ectopic mineralization/calcification, including but not limited to soft tissue, kidneys, intestine, myocardia, or lung, excepting calcified lymph nodes, lung nodules and asymptomatic vascular or cartilage/tendon calcifications
- •Administration of any investigational agent within 2 weeks prior to initial dosing with Debio 1347 (3 weeks for immune checkpoint inhibitors)
研究组 & 干预措施
Cohort 1: Debio 1347 (Biliary Tract Cancer)
Participants with biliary tract cancer were included in this cohort to receive Debio 1347 80 milligrams (mg) tablets, orally, once daily (QD), from Day 1 to Day 28 in 28-day cycles until the occurrence of disease progression or unacceptable toxicity (up to a median duration of 20 weeks).
干预措施: Debio 1347 (Drug)
Cohort 2: Debio 1347 (Urothelial Cancer)
Participants with urothelial cancer were included in this cohort to receive Debio 1347 80 mg tablets, orally, QD, from Day 1 to Day 28 in 28-day cycles until the occurrence of disease progression or unacceptable toxicity (up to a median duration of 5.86 weeks).
干预措施: Debio 1347 (Drug)
Cohort 3: Debio 1347 (All Other Solid Tumor Histologies)
Participants with all other solid tumor histologies were included in this cohort to receive Debio 1347 80 mg tablets, orally, QD, from Day 1 to Day 28 in 28-day cycles until the occurrence of disease progression or unacceptable toxicity (up to a median duration of 8.14 weeks).
干预措施: Debio 1347 (Drug)
结局指标
主要结局
Objective Response Rate (ORR) as Centrally Measured by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) Criteria
时间窗: Up to disease progression or end of study (up to 1 year and 9 months)
ORR was defined as the percentage of participants with a best overall response (BOR) of partial or complete response (PR or CR). BOR was defined as the best confirmed response observed from first administration of study drug until disease progression. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR was defined as ≥30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
次要结局
- Duration of Response (DOR) as Centrally Measured by Independent Review Committee (IRC)(Up to disease progression or end of study (up to 2 years and 9 months))
- Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Assessed by National Cancer Institute Common Terminology Criteria (NCI CTCAE) v5.0 and Serious Adverse Events (SAEs)(From first dose of study drug up to 30 days post last dose (Up to 2 years and 9 months))
- Area Under the Plasma Concentration-Time Curve Over the Dosing Interval at Steady State (AUCtau,ss) of Debio 1347 in Plasma(Predose and post dose up to Cycle 2 Day 28 (each cycle length = 28 days))
- Correlation of Debio 1347 Plasma Concentration (C) and QT Interval Corrected for Heart Rate Using Fridericia's Formula (QTcF)(Pre-dose on Days 14 and 28, and 1, 3, 7 hours post-dose on Day 28 of Cycle 1; pre-dose on Days 14 and 28, and 3 hours post-dose on Day 28 of Cycle 2 (each cycle length = 28 days))
- Progression-Free Survival (PFS) as Centrally Measured by Independent Review Committee (IRC)(From the start of the study up to disease progression or death (up to 2 years and 9 months))
- Disease Control Rate (DCR) as Centrally Measured by Independent Review Committee (IRC)(Up to disease progression or end of study (up to 2 years and 9 months))
- Overall Survival (OS)(Until death or loss to follow-up or end of study (up to 2 years and 9 months))
- Trough Concentration at Steady State (Ctrough,ss) of Debio 1347 in Plasma(Predose and post dose up to Cycle 2 Day 28 (each cycle length = 28 days))