A Phase 2 Study Evaluating Futibatinib (TAS 120) Plus Pembrolizumab in the Treatment of Advanced or Metastatic Urothelial Carcinoma
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 43
- 试验地点
- 18
- 主要终点
- Objective Response Rate (ORR)
研究概览
简要总结
The purpose of the trial is to evaluate the antitumor activity and confirm the safety for the combination of Fibroblast Growth Factor Receptor (FGFR) inhibitor futibatinib and anti-programmed cell death-1 (PD-1) antibody pembrolizumab in patients with advanced or metastatic urothelial cancer who are not candidates to receive a platinum-based treatment regimens.
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
- •Willing and able to provide written informed consent for the trial.
- •Age ≥ 18 years of age
- •Histologically confirmed advanced or metastatic urothelial carcinoma who have not received systemic treatment for advanced metastatic disease.
- •Cohort A: must have an FGFR3 mutation or FGFR1-4 fusion/rearrangement.
- •Cohort B: all other patients with UC (including patients with other FGFR or non-FGFR genetic aberrations and patients with wild-type [non-mutated] tumors)
- •Unfit for or intolerant to standard platinum-based chemotherapy.
- •Have an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 to
- •Adequate organ function.
- •Have a measurable disease per RECIST 1.1
排除标准
- •Have received prior therapy with anti-PD-1, anti-PD-L1/L2 agent or FGFR inhibitor.
- •History and/or current evidence of any of the following disorders:
- •Non-tumor related alteration of the calcium-phosphorus homeostasis that is considered clinically significant in the opinion of the Investigator.
- •Ectopic mineralization/calcification considered clinically significant in the opinion of the Investigator.
- •Retinal or corneal disorder considered clinically significant in the opinion of the Investigator.
- •Has received a live vaccine within 30 days prior to the first dose of study drug.
- •Have an active autoimmune disease that has required systemic treatment in the past 2 years.
- •Have a history of (noninfectious) pneumonitis that required steroids or has current pneumonitis.
- •Have had an allogenic tissue/ organ transplant.
- •Has known human immunodeficiency virus (HIV) and/or history of Hepatitis B or C infections, or known to be positive for Hepatitis B antigen (HBsAg)/ Hepatitis B virus (HBV) DNA or Hepatitis C Antibody or RNA.
- •Have known active central nervous system metastases and/or carcinomatous meningitis.
- •Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy.
- •Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.
研究组 & 干预措施
Cohort A
Participants with metastatic urothelial carcinoma (UC) and FGFR3 mutation or FGFR1-4 fusion/rearrangement received futibatinib 20 milligrams (mg), orally, once daily (QD), in a 21-day cycle for maximum duration of 590 days along with pembrolizumab 200 mg, intravenously (IV), every 3 weeks (Q3W), in a 21-day cycle for a maximum of 35 doses or a maximum duration of 2 years.
干预措施: Futibatinib (Drug)
Cohort A
Participants with metastatic urothelial carcinoma (UC) and FGFR3 mutation or FGFR1-4 fusion/rearrangement received futibatinib 20 milligrams (mg), orally, once daily (QD), in a 21-day cycle for maximum duration of 590 days along with pembrolizumab 200 mg, intravenously (IV), every 3 weeks (Q3W), in a 21-day cycle for a maximum of 35 doses or a maximum duration of 2 years.
干预措施: Pembrolizumab (Drug)
Cohort B
Participants with metastatic UC (including participants with other FGFR or non-FGFR genetic aberrations and participants with wild type [non-mutated] tumors) received futibatinib 20 mg, orally, QD, in a 21-day cycle for maximum duration of 563 days along with pembrolizumab 200 mg, IV, Q3W in a 21-day cycle for a maximum of 35 doses or a maximum duration of 2 years.
干预措施: Futibatinib (Drug)
Cohort B
Participants with metastatic UC (including participants with other FGFR or non-FGFR genetic aberrations and participants with wild type [non-mutated] tumors) received futibatinib 20 mg, orally, QD, in a 21-day cycle for maximum duration of 563 days along with pembrolizumab 200 mg, IV, Q3W in a 21-day cycle for a maximum of 35 doses or a maximum duration of 2 years.
干预措施: Pembrolizumab (Drug)
结局指标
主要结局
Objective Response Rate (ORR)
时间窗: Up to 38 months
ORR was defined as the proportion of participants experiencing a best overall response of partial response (PR) or complete response (CR) according to response evaluation criteria in solid tumors, version 1.1 (RECIST 1.1) criteria based on investigator assessment. Evaluation of target lesions defined a CR as the disappearance of all target lesions and non-target lesions (if applicable), and normalization of tumor marker level; PR was defined as at least a 30 percent (%) decrease in the sum of diameters of the target lesions, taking as a reference the baseline sum of diameters for all target lesion assessments. Evaluation of non-target lesions was defined as the persistence of one or more non-target lesion(s) and/or maintenance of tumor marker level above the normal limits. For both target and non-target evaluations, any pathological lymph node must have had a reduction in short axis to less than (\<)10 millimeters (mm).
次要结局
- Disease Control Rate (DCR)(Up to 38 months)
- Duration of Response (DOR)(Up to 38 months)
- Overall Survival (OS)(Up to 38 months)
- Progression-free Survival (PFS)(Up to 38 months)
- Number of Participants With Treatment Emergent Adverse Events (TEAEs)(Up to 38 months)