A Phase 2, Open-label, Multi-centre, Multi-national Interventional Trial to Evaluate the Efficacy and Safety of Erdafitinib (ERDA) Monotherapy and Erdafitinib (ERDA) and Cetrelimab (CET) Combination as Neoadjuvant Treatment in Cisplatin-ineligible Patients With Muscle-invasive Bladder Cancer (MIBC) Whose Tumours Express Fibroblast Growth Factor Receptor ( FGFR ) Gene Alterations
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 90
- 试验地点
- 23
- 主要终点
- Pathological complete response (pCR)
研究概览
简要总结
Erdafitinib (ERDA) alone or in combination with cetrelimab (CET) as neoadjuvant treatment (prior to surgery) in subjects with muscle-invasive bladder cancer (MIBC) whose tumours express Fibroblast Growth Factor Receptor (FGFR )gene alterations and are ineligible for or refuse cisplatin based neoadjuvant chemotherapy.
详细描述
The aim of the study is to assess the antitumor activity measured as ypT0 rate, defined as no evidence of residual disease based on pathological review of the surgical specimen (pCR) and tumour downstaging (<ypT2). Patients must have a MIBC (cT2-T4a N0/N1 M0) who harbour selected FGFR alterations stated in the protocol and are either ineligible for or refuse cisplatin-based neoadjuvant chemotherapy, as defined by consensus criteria (see 6.1 Inclusion criteria).
Once it is confirmed that the subjects fulfil the eligibility criteria and have signed the informed consent form, they will receive erdafitinib alone (cohort 1) or erdafitinib in combination with cetrelimab (cohort 2).
Patients will receive neoadjuvant treatment with erdafitinib alone (cohort 1) or erdafitinib plus cetrelimab (cohort 2) before proceeding to Radical Cystectomy (RC) (to be performed within 2 - 6 weeks after the last study drug treatment)
Cohort 1: patients will receive erdafitinib Cohort 2: patients will receive erdafitinib in combination with cetrelimab intravenously (IV)
Radiological assessment: A Computed Tomography /Magnetic Resonance Imaging and/or Positron Emission Tomography (per standard local imaging practices) will be scheduled as follow:
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
- •Written informed consent stating that he or she understands the purpose of the study and the procedures involved and agrees to participate in the study.
- •Histologically confirmed diagnosis of MIBC (Stage T2-4a N0/N1 M0) obtained via a diagnostic or maximal Transurethral Resection of Bladder Tumor (TURBT) performed no later than 3 months prior to start the screening visit.
- •Pure or predominant (≥50%) urotelial Cancer (UC) histology as determined at the local site.
- •Age ≥ 18 years.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
- •Decline or ineligible ("unfit") for cisplatin-based chemotherapy
- •Presence of a selected FGFR alteration on analysis of tumour biopsy
- •Adequate organ function
- •No other malignancy
- •Willingness to avoid pregnancy or fathering children
排除标准
- •Clinical evidence of N2-N3 tumours or metastatic bladder cancer.
- •Has tumour with any neuroendocrine or small cell component.
- •Patients who are not considered fit for cystectomy or reject cystectomy.
- •Prior FGFR-targeted or an immune checkpoint inhibitor (antiPD1/PDL1 )systemic therapy.
- •Prior systemic therapy, radiation therapy, or surgery for bladder cancer
研究组 & 干预措施
Erdafitinib (ERDA) monotherapy
Patients will receive treatment neoadjuvant with erdafitinib alone (cohort 1: Erdafitinib) before proceeding to radical cystectomy (RC) (to be performed within 2 - 6 weeks after the end of treatment)
干预措施: Erdafitinib monotherapy (Drug)
Erdafitinib (ERDA) and Cetrelimab (CET) combination
Patients will receive treatment neoadjuvant with erdafitinib + cetrelimab (cohort 2: Erdafitinib + Cetrelimab) before proceeding to radical cystectomy (RC) (to be performed within 2 - 6 weeks after the end of treatment)
干预措施: Cetrelimab and Erdafitinib combination (Drug)
结局指标
主要结局
Pathological complete response (pCR)
时间窗: After a maximum of 30 weeks from the start of treatment (First Followup visit ) on specimens obtained during radical cystectomy.
Defined as no evidence of residual disease based on pathological review of the surgical specimen.It is defined as the proportion of patients whose pathological staging was ypT0N0M0 as assessed using specimens obtained post radical cystectomy following the study intervention.
Pathological downstaging response <ypT2
时间窗: After a maximum of 30 weeks from the start of treatment (First Followup visit ) on specimens obtained during radical cystectomy.
Defined as no microscopic evidence of residual disease in the bladder (ypT0) or evidence of non-muscle invasive residual disease including ypTa, ypTis, ypT1, based on histological evaluation of the resected bladder specimen collected during cystectomy (post-treatment)."
次要结局
- Rate of delay of surgery(During treatment (27 months) and follow-up period (36 months))
- Rate of pathological downstaging (pDS)(During treatment (27 months))
- Overall Survival(During follow-up period (36 months))
- Adverse events.(During treatment (27 months) and follow-up period (36 months))
- Event-free Survival rate.(During follow-up period (36 months))
- Overall Response Rate(During treatment (27 months))