A Phase 2, Open-Label, Randomized, Multicenter Study to Evaluate the Efficacy and Safety of Pemigatinib Plus Pembrolizumab Versus Pemigatinib Alone Versus Standard of Care as First-Line Treatment for Metastatic or Unresectable Urothelial Carcinoma in Cisplatin-Ineligible Participants Whose Tumors Express FGFR3 Mutation or Rearrangement (FIGHT-205)
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 7
- 试验地点
- 79
- 主要终点
- Progression-free Survival (PFS)
研究概览
简要总结
The purpose of this study is to evaluate the safety and efficacy of pemigatinib plus pembrolizumab or pemigatinib alone versus the standard of care for participants with metastatic or unresectable urothelial carcinoma who are not eligible to receive cisplatin, are harboring FGFR3 mutation or rearrangement, and who have not received prior treatment.
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 documented metastatic or unresectable urothelial carcinoma. Both transitional cell and mixed transitional cell histologies are allowed, provided urothelial component is ≥ 50%.
- •At least 1 measurable target lesion per RECIST v1.
- •Must be ineligible to receive cisplatin. Patients ineligible for any platinum-based chemotherapy are allowed.
- •Known FGFR3 mutation or rearrangement confirmed by the central laboratory prior to randomization.
- •Central laboratory test result of PD-L1 status is mandatory at screening.
- •Have received no prior systemic chemotherapy for metastatic or unresectable urothelial carcinoma (except adjuvant platinum-based chemotherapy following radical cystectomy, with recurrence > 12 months from completion of therapy, or neo-adjuvant platinum-based chemotherapy, with recurrence > 12 months since completion of therapy).
- •Eastern Cooperative Oncology Group (ECOG) performance status 0 to
- •Willingness to avoid pregnancy or fathering children.
排除标准
- •Prior receipt of a selective FGFR inhibitor for any indication or reason.
- •Prior receipt of an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent, or with an agent directed to another co-inhibitory T-cell receptor.
- •Receipt of anticancer medications or investigational drugs for unresectable and/or metastatic disease.
- •Concurrent anticancer therapy, except for treatment allowed per protocol.
- •Has disease that is suitable for local therapy administered with curative intent.
- •Has tumor with any neuroendocrine or small cell component.
- •Current evidence of clinically significant corneal or retinal disorder as confirmed by ophthalmologic examination.
- •Has received prior radiotherapy to a metastatic site without the use of chemotherapy radiosensitization within 3 weeks of the first dose of study treatment, with the exception of palliative radiotherapy to bone lesions, which is allowed if completed 2 weeks before the start of study treatment.
- •Has central nervous system metastases, unless the participant has completed local therapy (eg, whole brain radiation therapy, surgery, radiosurgery) and has discontinued use of corticosteroids for this indication for at least 4 weeks before starting treatment in this study.
- •Known additional malignancy that is progressing or required active treatment within the past 3 years
- •Laboratory values outside the protocol-defined range at screening.
- •Clinically significant or uncontrolled cardiac disease.
- •History of autoimmune disease that has required systemic treatment in past 2 years.
研究组 & 干预措施
Pemigatinib + Pembrolizumab
Combination of pemigatinib (13.5 milligrams [mg] once a day orally) plus pembrolizumab (200 mg every 3 weeks [Q3W] intravenously [IV])
干预措施: Pemigatinib (Drug)
Pemigatinib + Pembrolizumab
Combination of pemigatinib (13.5 milligrams [mg] once a day orally) plus pembrolizumab (200 mg every 3 weeks [Q3W] intravenously [IV])
干预措施: Pembrolizumab (Drug)
Pemigatinib
Pemigatinib (13.5 mg once a day orally) alone
干预措施: Pemigatinib (Drug)
Standard of Care
Either gemcitabine plus carboplatin or pembrolizumab as standard of care. Gemcitabine 1000 mg/meters squared (m^2) IV over 30 minutes on Days 1 and 8, followed by carboplatin (dosed to target area under the concentration-time curve [AUC] of 5 mg/milliliters [mL]/minute [min] or 4.5 mg/mL/min if required per local guidelines) on Day 1 or 2 of each 3-week cycle. Pembrolizumab 200 mg IV on Day 1 of each 21-day treatment cycle for up to 35 cycles or disease progression.
干预措施: Gemcitabine (Drug)
Standard of Care
Either gemcitabine plus carboplatin or pembrolizumab as standard of care. Gemcitabine 1000 mg/meters squared (m^2) IV over 30 minutes on Days 1 and 8, followed by carboplatin (dosed to target area under the concentration-time curve [AUC] of 5 mg/milliliters [mL]/minute [min] or 4.5 mg/mL/min if required per local guidelines) on Day 1 or 2 of each 3-week cycle. Pembrolizumab 200 mg IV on Day 1 of each 21-day treatment cycle for up to 35 cycles or disease progression.
干预措施: Carboplatin (Drug)
结局指标
主要结局
Progression-free Survival (PFS)
时间窗: up to 130 days
PFS was defined as the time from the randomization date until the date of disease progression (as measured by a blinded independent central review \[BICR\] per Response Evaluation Criteria in Solid Tumors version 1.1 \[RECIST v1.1\]) or death due to any cause, whichever occurred first.
次要结局
- Number of Participants With Treatment-emergent Adverse Events(up to 178 days)
- Change From Baseline in the EQ-5D-5L EQ Visual Analog Scale Score(Baseline; up to 160 days)
- Overall Survival (OS)(up to 225 days)
- Objective Response Rate (ORR)(up to 148 days)
- EORTC QLQ-C30 Score(up to 160 days)
- Duration of Response (DOR)(up to 148 days)
- Change From Baseline in the EORTC QLQ-C30 Score(Baseline; up to 160 days)
- Number of Participants With the Indicated EQ-5D-5L Dimension Scores(up to 160 days)