An Open-label Multi-cohort Phase 1b/2 Study of Derazantinib and Atezolizumab in Patients With Urothelial Cancer Expressing Activating Molecular FGFR Aberrations
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 95
- 试验地点
- 66
- 主要终点
- Recommended Phase 2 Dose (RP2D) of Derazantinib-atezolizumab in Combination Based on DLT Criteria, Safety and Efficacy Data (Substudy 2)
研究概览
简要总结
The purpose of this study was to evaluate efficacy of derazantinib monotherapy or derazantinib-atezolizumab in combination in patients with advanced urothelial cancer harboring fibroblast growth factor receptor (FGFR) genetic aberrations (GA) of various clinical stages of disease progression and prior treatments.
详细描述
The study comprised five open-label substudies (1-5) in patients with advanced urothelial cancer harboring FGFR GA (with the exception of substudy 2 which did not require a FGFR GA) who were treated by derazantinib monotherapy or derazantinib in combination with atezolizumab. The study enrolled patients with cisplatin-ineligible status, or patients whose disease progressed after either first-line treatment or prior treatment with FGFR inhibitors.
研究设计
- 研究类型
- Interventional
- 分配方式
- 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
- •Histologically-confirmed transitional cell carcinoma of the urothelium of the upper or lower urinary tract
- •Recurrent or progressing stage IV disease, or surgically unresectable, recurrent or progressing disease
- •Documented central FGFR genetic aberration (FGFR1, FGFR2, or FGFR3 mutations / short variants and rearrangements / fusions) (Note; Substudy 2 started with patients requiring an FGFR GA, but this requirement was removed from the protocol later on)
- •Measurable disease, as defined by the Investigator using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria
- •Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1 or 2
- •Adequate organ functions as indicated by Screening visit local laboratory values
排除标准
- •Receipt of prior cancer treatment within specific interval periods
- •Concurrent evidence of any clinically significant corneal or retinal disorder
- •History of clinically significant cardiac disorders
- •Known CNS metastases
- •Concurrent uncontrolled or active infection with human immunodeficiency virus
- •Active hepatitis B or chronic hepatitis B without current antiviral therapy
- •Active hepatitis C
- •Active tuberculosis
- •Severe bacterial, fungal, viral and/or parasitic infections on therapeutic oral or IV medication at the time of first dose of study drug administration
研究组 & 干预措施
Substudy 1: Derazantinib 300 mg once daily
Patients with urothelial cancer were treated with derazantinib 300 mg once daily
干预措施: Derazantinib 300 mg once daily monotherapy (Drug)
Substudy 2 (Dose-Level 1): Derazantinib 200 mg once daily + atezolizumab 1200 mg
Patients with any solid tumors were treated with derazantinib 200 mg once daily in combination with atezolizumab 1200 mg given every 3 weeks as intravenous (IV) infusion
干预措施: Derazantinib 200 mg once daily + atezolizumab 1200 mg (Drug)
Substudy 2 (Dose-Level 2): Derazantinib 300 mg once daily + atezolizumab 1200 mg
Patients with any solid tumors were treated with derazantinib 300 mg once daily in combination with atezolizumab 1200 mg given every 3 weeks as IV infusion
干预措施: Derazantinib 300 mg once daily+ atezolizumab 1200 mg (Drug)
Substudy 3: Derazantinib 200 mg twice daily + atezolizumab 1200 mg
Patients with urothelial cancer were treated with derazantinib 200 mg twice daily in combination with atezolizumab 1200 mg given every 3 weeks as IV infusion
干预措施: Derazantinib 200 mg twice daily + atezolizumab 1200 mg (Drug)
Substudy 4 (Cohort 4a):Derazantinib 300 mg once daily
Patients with FGFR inhibitor resistant urothelial cancer were treated with derazantinib 300 mg once daily
干预措施: Derazantinib 300 mg once daily monotherapy (QD) (Drug)
Substudy 4 (Cohort 4b):Derazantinib 300 mg once daily + atezolizumab 1200 mg
Patients with urothelial cancer were treated with derazantinib 300 mg once daily in combination with atezolizumab 1200 mg given every 3 weeks as IV infusion
干预措施: Derazantinib 300 mg once daily + atezolizumab 1200 mg (Drug)
Substudy 5: Derazantinib 200 mg twice daily
Patients with urothelial cancer were treated with derazantinib 200 mg twice daily
干预措施: Derazantinib 200 mg twice daily monotherapy (Drug)
结局指标
主要结局
Recommended Phase 2 Dose (RP2D) of Derazantinib-atezolizumab in Combination Based on DLT Criteria, Safety and Efficacy Data (Substudy 2)
时间窗: From first dose up to 2 years
The RP2D was determined by a joint decision taken by the Independent Data Monitoring Committee (IDMC), Investigators, and the Sponsor in reviewing the aggregate of DLT and AE data, and considering efficacy data
Objective Response Rate (ORR) Based on RECIST 1.1 (Substudies 1,3,4 and 5)
时间窗: From first dose up to 2 years
ORR was defined as the proportion of patients who achieved a confirmed clinical response (CR) or partial response (PR) by blinded investigator central review (BICR) using the internationally recognized criteria for the radiological assessment in tumor response of solid tumors (RECIST) Version 1.1
Number of Patients With Dose-limiting Toxicities (DLTs) in Substudy 2
时间窗: From first dose up to 2 years
In Substudy 2, the primary endpoint was the number of patients with DLTs. A DLT was defined as a clinically-significant adverse event (AE) or abnormal laboratory value assessed as unrelated to disease progression, intercurrent illness, or concomitant medications. Any DLT had to be a toxicity considered at least possibly related to derazantinib or the combination of derazantinib and atezolizumab
次要结局
- ORR Based on RECIST 1.1 (Substudy 2)(From first dose up to 2 years)
- Number of Patients With at Least Grade 3 Adverse Events (AEs)(From first dose and until 90 days following the last dose)
- Disease Control Rate (DCR) Per RECIST 1.1 in All Substudies(From first dose up to 2 years)
- Duration of Response (DOR) Per RECIST 1.1(From first dose up to 2 years)
- Progression-free Survival (PFS) by RECIST in All Substudies(From first dose up to 2 years)
- Overall Survival (OS) in All Substudies(From first dose up to 2 years)