A Phase 1b/2 Study of Derazantinib as Monotherapy and Combination Therapy With Paclitaxel, Ramucirumab or Atezolizumab in Patients With HER2-negative Gastric Adenocarcinoma Expressing FGFR2 Genetic Aberrations
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 47
- 试验地点
- 81
- 主要终点
- Progression-free Survival at 4 Months (PFS4) in Substudy 1 in Cohort 1.3
研究概览
简要总结
The purpose of this study was to evaluate the efficacy of derazantinib monotherapy or derazantinib in combination with paclitaxel and ramucirumab in patients with gastric adenocarcinoma (GAC) i.e. with human epidermal growth factor receptor 2 (HER2)-negative adenocarcinoma of the stomach or gastro-esophageal junction harboring fibroblast growth factor receptor 2 (FGFR2) genetic aberrations (GA).
详细描述
The study comprised two open-label substudies in patients with HER2-negative adenocarcinoma of the stomach or gastro-esophageal junction harboring FGFR2 gene translocations, FGFR2 gene amplifications, or FGFR1-3 mutations.
In Substudy 1, GAC patients with specified FGFR GAs, after either first- or second-line treatment, and no approved treatment alternative were treated with derazantinib 300 mg once daily or 200 mg twice daily, with the aim of evaluating the safety, tolerability, and efficacy of derazantinib monotherapy in this patient population.
In Substudy 2, GAC patients with specified FGFR GAs after standard first-line treatment, were treated with a derazantinib-paclitaxel-ramucirumab combination with the aim of evaluating the safety, tolerability, and efficacy of the combination therapy and determining the recommended phase 2 dose (RP2D).
The study originally planned to include three substudies but was prematurely terminated for administrative reasons before the third substudy (including combination therapy with derazantinib plus atezolizumab) was initiated.
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
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Substudy 1: Cohort 1.1 Derazantinib 300 mg once daily
Patients with FGFR2 fusions or amplifications were treated with 300 mg Derazantinib monotherapy once daily
干预措施: Derazantinib (Drug)
Substudy 1: Cohort 1.2 Derazantinib 300 mg once daily
Patients with FGFR1-3 mutations were treated with 300 mg Derazantinib monotherapy once daily
干预措施: Derazantinib (Drug)
Substudy 1: Cohort 1.3 Derazantinib 200 mg twice daily
Patients with FGFR fusions, amplifications or mutations were treated with 200 mg Derazantinib monotherapy twice daily
干预措施: Derazantinib (Drug)
Substudy 2: Derazantinib 200 mg once daily +Paclitaxel+ Ramucirumab
Patients with FGFR fusions, amplifications or mutations were treated with 200 mg Derazantinib once daily in combination with Paclitaxel and Ramucirumab
干预措施: Derazantinib-paclitaxel-ramucirumab combination (Drug)
Substudy 2: Derazantinib 300 mg once daily+Paclitaxel+ Ramucirumab
Patients with FGFR fusions, amplifications or mutations were treated with 300 mg Derazantinib once daily combination with Paclitaxel and Ramucirumab
干预措施: Derazantinib-paclitaxel-ramucirumab combination (Drug)
结局指标
主要结局
Progression-free Survival at 4 Months (PFS4) in Substudy 1 in Cohort 1.3
时间窗: From first dose and up to 4 months
PFS4 was defined by the percentage of patients alive and free of disease progression (defined as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions) by BICR per RECIST. 1.1. Patients in this Cohort had FGFR fusions, amplifications or mutations GAC
Recommended Phase 2 Dose (RP2D) in Substudy 2 (Derazantinib-paclitaxel-ramucirumab in Combination)
时间窗: From first dose and up to 18 months
RP2D was determined from safety and tolerability according to the aggregate of dose-limiting toxicity criteria and adverse event (AE) data, and considering further pharmacokinetic and efficacy data of the derazantinib-paclitaxel-ramucirumab combination in patients with FGFR fusions, amplifications or mutations GAC.
Objective Response Rate (ORR) in Substudy 1 (in Cohorts 1.1 and 1.2)
时间窗: From first dose and up to 18 months
ORR was defined by the percentage of patients with confirmed complete response (CR, which means disappearance of all target lesions) or partial response (PR, which means \>=30% decrease in the sum of the longest diameter of target lesions) by blinded independent central review (BICR) using the internationally recognized criteria for the radiological assessment in tumor response of solid tumors (RECIST 1.1). Overall Response (OR) = CR + PR. The patients in Cohort 1.1 had FGFR2 fusions or amplification gastric adenocarcinoma (GAC) and FGFR1-3 mutations GAC in Cohort 1.2.
次要结局
- ORR in Substudy 1 in Cohort 1.3(From first dose and up to 9 months)
- OS in Substudy 2(From first dose and up to 15 months)
- ORR in Substudy 2(From first dose and up to 15 months)
- DCR in Substudy 2(From first dose and up to 15 months)
- DOR in Substudy 2 (Separate and Combined Cohorts)(From first dose and up to 15 months)
- PFS in Substudy 2(From first dose and up to 15 months)
- Number of Patients With at Least Grade 3 Treatment-emergent Adverse Events (TEAEs)(TEAEs defined as AEs which were assessed per patient from the patient's first dose and until 90 days after the last dose, which corresponded up to 19 months)
- Disease Control Rate (DCR) in Substudy 1: Cohort 1.1, 1.2 and 1.3 and Combined Cohorts(From first dose and up to 18 months)
- PFS in Substudy 1 in Cohort 1.3(From first dose and up to 9 months)
- Overall Survival (OS) in Substudy 1 in Cohort 1.3(From first dose and up to 9 months)