A Phase III, Randomized, Controlled, Global Multicenter Study to Evaluate the Efficacy and Safety of Oral Tinengotinib VS Physician's Choice in Subjects With FGFR-altered, Chemotherapy- and FGFR Inhibitor-Cholangiocarcinoma
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 200
- 试验地点
- 142
- 主要终点
- Part A: Incidence, duration, and severity of adverse events (AEs)
研究概览
简要总结
This study is a Phase III, Randomized, Controlled, Global Multicenter Study to Evaluate the Efficacy and Safety of Oral Tinengotinib versus Physician's Choice in Subjects with Fibroblast Growth Factor Receptor (FGFR)-altered, Chemotherapy- and FGFR Inhibitor-Refractory/Relapsed Cholangiocarcinoma
详细描述
Approximately 200 subjects will be enrolled. Eligible subjects will be randomized in a 2:2:1 ratio to receive tinengotinib 8 mg QD, tinengotinib 10 mg QD or Physician's Choice in Part A; and eligible subjects will be randomized in a 2:1 ratio to receive the recommended Part B dose or selected dose or Physician's Choice in Part B.
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
- •≥ 18 years of age at the time of signing the informed consent form (ICF).
- •Histologically or cytologically confirmed CCA/adenocarcinoma of biliary origin with radiological evidence of unresectable or metastatic disease.
- •Documentation of FGFR2 fusion/rearrangement gene status
- •Subjects must have received at least one line of prior chemotherapy and exactly one FDA approved FGFR inhibitor.
排除标准
- •Prior receipt of two or more FGFR inhibitors, either approved or investigational drugs.
- •Subjects with known brain or central nervous system (CNS) metastases that have radiologically or clinically progressed in the 28 days prior to initiation of therapy. Subjects with asymptomatic brain/CNS metastases or treated brain/CNS metastases that have been clinically stable for 14 days on steroids without escalation of steroids are eligible for enrollment.
- •Subjects with a known concurrent malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, carcinoma in situ of the cervix, or other noninvasive or indolent malignancy, including those that have previously undergone potentially curative therapy.
- •Subjects who have received prior systemic therapy or investigational study drug ≤ 5 half-lives or 14 days, whichever is shorter, prior to starting the study drug or who have not recovered (grade ≤ 1 or at pretreatment baseline except tolerable grade 2 alopecia, fatigue/asthenia, and neuropathy due to trauma) from adverse events (AEs) of prior therapy.
- •Concurrent anticancer therapy including chemo-, immune-, or radiotherapy. Hormone therapy may be allowed with Sponsor approval.
- •Subjects who have received wide field radiotherapy ≤ 4 weeks or limited field radiation for palliation ≤ 2 weeks prior to starting the study drug or who have not recovered from AEs of prior therapy.
- •Subjects with uncontrolled hypertension (defined as blood pressure of ≥ 150 mm Hg systolic and/or ≥ 90 mm Hg diastolic despite adequate treatment with antihypertensive medications at screening)
研究组 & 干预措施
Physician's Choice
Physician's Choice treatments include FOLFOX or FOLFIRI
干预措施: Physician's Choice (Drug)
Tinengotinib 8 mg QD
Tinengotinib will be administered in 28-day cycles.
干预措施: Tinengotinib 8 mg (Drug)
Tinengotinib 10 mg QD
Tinengotinib will be administered in 28-day cycles.
干预措施: Tinengotinib 10 mg (Drug)
结局指标
主要结局
Part A: Incidence, duration, and severity of adverse events (AEs)
时间窗: Up to 30 days from study discontinuation
As assessed per Common Terminology Criteria for Adverse Events (CTCAE) v5.0 (or the most current version).
Part B: PFS by BICR
时间窗: From first study drug administration until the date of first documented progression assessed by BICR or date of death from any cause, whichever came first, assessed up to 24 months
Progression-free survival (PFS) by BICR: PFS is defined as the time from date of randomization to the date of first documented disease progression as assessed by BICR per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, or date of death due to any cause, whichever is earlier.
次要结局
- Part B: Objective Response Rate (ORR) by BICR and by Investigator:(Through study completion, an average of 9 months.)
- Part B: Duration of Response (DOR) by BICR and by Investigator(Through study completion, an average of 9 months.)
- Part A: ORR by Investigator(Through study completion, an average of 9 months.)
- Part B:Overall Survival (OS)(From first study drug administration until the date of death from any cause, assessed up to 24 months.)
- Part B: PFS by Investigators per RECIST v1.1.(From first study drug administration until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months.)
- Part A: DOR by Investigator(Through study completion, an average of 9 months.)