A Phase 2 Study of Erdafitinib in Subjects With Advanced Solid Tumors and FGFR Gene Alterations
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 316
- 试验地点
- 321
- 主要终点
- Broad Panel and Pediatric Cohorts: Objective Response Rate (ORR) Based on Response Assessment in Neuro-Oncology (RANO) as Assessed by Independent Review Committee (IRC)
研究概览
简要总结
The purpose of this study is to evaluate the efficacy of erdafitinib in terms of overall response rate (ORR) in adult and pediatric participants with advanced solid tumors with fibroblast growth factor receptor (FGFR) alterations (mutations or gene fusions). It will also evaluate ORR in pediatric participants with advanced solid tumors and FGFR alterations.
详细描述
Erdafitinib is a selective and potent pan FGFR 1-4 inhibitor with demonstrated clinical activity in participants with metastatic urothelial cancer and cholangiocarcinoma identified to have alterations in the FGFR pathway. This study targets the underlying altered biology of FGFR-driven tumors irrespective of solid tumor histology subtype. The study consists of screening phase, treatment phase and the post treatment follow-up phase (from the end of treatment visit until the participant has died, withdraws consent, is lost to follow-up, or the end of study, whichever comes first). End of study is considered as the time when the last participant receives the last dose of study drug on the study and either all pediatric participants are off study or until the most recently enrolled pediatric participant still participating in the study has 6 months of follow-up, whichever occurs first. Currently this study is recruiting pediatric participants only.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 6 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologic demonstration of an unresectable, locally advanced, or metastatic solid tumor malignancy with an fibroblast growth factor receptor (FGFR) mutation or FGFR gene fusion
- •Measurable disease
- •Participant must have received at least one prior line of systemic therapy in the advanced, unresectable, or metastatic setting; or is a child or adolescent participant with a newly-diagnosed solid tumor and no acceptable standard therapies
- •Documented progression of disease, defined as any progression that requires a change in treatment, prior to full study screening
排除标准
- •Has had prior chemotherapy, targeted therapy, or treatment with an investigational anticancer agent within 15 days or less than or equal to (<=) 5 half-lives of the agent (whichever is longer) and up to a maximum of 30 days before the first dose of erdafitinib
- •The presence of FGFR gatekeeper and resistance mutations
- •Histologic demonstration of urothelial carcinoma
- •Hematologic malignancy (i.e., myeloid and lymphoid neoplasms
- •For non-small cell lung cancer participants only: pathogenic somatic mutations or gene fusions in the following genes: EGFR, ALK, ROS1, NTRK, BRAF V600E and KRAS
- •Active malignancies other than for disease requiring therapy
研究组 & 干预措施
Erdafitinib
Participants with fibroblast growth factor receptor (FGFR) mutations and FGFR gene fusions will receive a dose of erdafitinib oral tablets until disease progression, intolerable toxicity, withdrawal of consent, decision by the investigator to discontinue treatment, or end of data collection timepoint if there is clinical benefit in the opinion of the investigator, has been achieved.
干预措施: Erdafitinib (Drug)
结局指标
主要结局
Broad Panel and Pediatric Cohorts: Objective Response Rate (ORR) Based on Response Assessment in Neuro-Oncology (RANO) as Assessed by Independent Review Committee (IRC)
时间窗: Baseline (Cycle 1 Day 1 [each cycle of 21 days]) up to 4 years
ORR is defined as the percentage of participants who achieved a complete response (CR), or partial response (PR) based on Response Assessment in Neuro-Oncology (RANO) criteria. According to RANO criteria whereby overall RANO response is based on both radiographic response (CR: disappearance of all target lesions; PR: sum of products of diameters \[SPD\] decreased by \>=50 percent \[%\] from baseline value) and clinical performance status with steroid dose information.
Core Panel Cohort: Objective Response Rate (ORR) Based on Response Assessment in Neuro-Oncology (RANO) as Assessed by Independent Review Committee (IRC)
时间窗: Baseline (Cycle 1 Day 1 [each cycle of 21 days]) up to 4 years
ORR is defined as the percentage of participants who achieved a CR, or PR based on RANO criteria. According to RANO criteria whereby overall RANO response is based on both radiographic response (CR: disappearance of all target lesions; PR: sum of products of diameters \[SPD\] decreased by \>=50 percent \[%\] from baseline value) and clinical performance status with steroid dose information. The core panel cohort is a subgroup of the broad panel cohort with a select panel of pre-specified FGFR markers: FGFR3 mutations (S249C;Y373C; R248C; G370C); FGFR2 mutations (C382R); FGFR3 fusions (FGFR3-TACC3); FGFR2 fusions (FGFR2-BICC1; FGFR2-TACC2).
次要结局
- Objective Response Rate (ORR) as Assessed by Investigators Assessment(Baseline (Cycle 1 Day 1 [each cycle of 21 days]) up to 5 years 4 months)
- Duration of Responses (DOR)(Baseline (Cycle 1 Day 1 [each cycle of 21 days]) up to 5 years 4 months)
- Disease Control Rate (DCR)(Baseline (Cycle 1 Day 1 [each cycle of 21 days]) up to 5 years 4 months)
- Clinical Benefit Rate (CBR)(Baseline (Cycle 1 Day 1 [each cycle of 21 days]) up to 5 years 4 months)
- Progression-free Survival (PFS)(Baseline (Cycle 1 Day 1 [each cycle of 21 days]) up to 5 years 4 months)
- Overall Survival (OS)(Baseline (Cycle 1 Day 1 [each cycle of 21 days]) up to 5 years 4 months)
- Number of Participants With Adverse Events (AEs)(Baseline (Cycle 1 Day 1 [each cycle of 21 days]) up to 5 years 4 months)
- Number of Participants With Adverse Events (AEs) by Severity(Baseline (Cycle 1 Day 1 [each cycle of 21 days]) up to 5 years 4 months)
- Pediatric Cohort: Plasma Concentration of Erdafitinib(Baseline (Cycle 1 Day 1 [each cycle of 21 days]) up to 5 years 4 months)
- Change From Baseline in European Organization for Research and Treatment of Cancer Quality-of-life Questionnaire Core 30 (EORTC-QLQ-C30) for Participants >=18 Years(Baseline (Cycle 1 Day 1 [each cycle of 21 days]) up to 5 years 4 months)
- Change From Baseline in Pediatric Functional Assessment Of Cancer Therapy-Brain (Peds FACT-Br)(Baseline (Cycle 1 Day 1 [each cycle of 21 days]) up to 5 years 4 months)
- Change From Baseline in Patient Global Impression of Symptom Severity (PGIS)(Baseline (Cycle 1 Day 1 [each cycle of 21 days]) up to 5 years 4 months)
- Change From Baseline in Patient Global Impression of Change (PGIC)(Baseline (Cycle 1 Day 1 [each cycle of 21 days]) up to 5 years 4 months)
- Change From Baseline in European Quality of Life -5 Dimensions-5 Levels (EQ-5D-5L)(Baseline (Cycle 1 Day 1 [each cycle of 21 days]) up to 5 years 4 months)