A Phase 3, Open-Label, Randomized, Active-Controlled, Multicenter Study to Evaluate the Efficacy and Safety of Pemigatinib Versus Gemcitabine Plus Cisplatin Chemotherapy in First-Line Treatment of Participants With Unresectable or Metastatic Cholangiocarcinoma With FGFR2 Rearrangement (FIGHT-302)
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 167
- 试验地点
- 215
- 主要终点
- Randomized Treatment Period: Progression-free Survival (PFS)
研究概览
简要总结
The purpose of this study is to evaluate the efficacy and safety of pemigatinib versus gemcitabine plus cisplatin chemotherapy in first-line treatment of participants with unresectable or metastatic cholangiocarcinoma with FGFR2 rearrangement.
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
- •Male and female participants at least 18 years of age at the time of signing the informed consent form (ICF).
- •Histologically or cytologically confirmed cholangiocarcinoma that is previously untreated and considered unresectable and/or metastatic (Stage IV per the American Joint Committee on Cancer (AJCC) Cancer Staging Manual).
- •Radiographically measurable or evaluable disease by CT or MRI per RECIST v1.1 criteria.
- •Eastern Cooperative Oncology Group performance status 0 to
- •Documented FGFR2 rearrangement.
- •Willingness to avoid pregnancy or fathering children.
排除标准
- •Received prior anticancer systemic therapy for unresectable and/or metastatic disease (not including adjuvant/neo-adjuvant treatment completed at least 6 months prior to enrollment, and participants that have received treatment for locally advanced disease with trans-arterial chemoembolization or selective internal radiation therapy, if clear evidence of radiological progression is observed before enrollment, or enrolled as of Amendment 6 (or Amendment 5-JP2) and the participant received 1 cycle of gemcitabine plus cisplatin [the start of study drug {Cycle 1 Day 1} must be at least 14 days and ≤ 4 weeks {28 days} from the last dose of gemcitabine plus cisplatin]).
- •Child-Pugh B and C.
- •Toxicities related to prior therapy(ies) must be Common Terminology Criteria for Adverse Events (CTCAE) v5.0 ≤ Grade 1 at the time of screening.
- •Concurrent anticancer therapy, other than the therapies being tested in this study.
- •Participant is a candidate for potentially curative surgery.
- •Current evidence of clinically significant corneal (including but not limited to bullous/band keratopathy, corneal abrasion, inflammation/ulceration, and keratoconjunctivitis) or retinal disorder (including but not limited to central serous retinopathy, macular/retinal degeneration, diabetic retinopathy, retinal detachment) as confirmed by ophthalmologic examination.
- •Radiation therapy administered within 4 weeks of enrollment/randomization/first dose of study treatment.
- •Known central nervous system (CNS) metastases or history of uncontrolled seizures.
- •Known additional malignancy that is progressing or requires active treatment (exceptions: basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy).
- •Laboratory values at screening outside the protocol-defined range.
- •History of calcium and phosphate hemostasis disorder or systemic mineral imbalance with ectopic calcification of soft tissues (exception: commonly observed calcifications in soft tissues, such as the skin, kidney, tendons or vessels due to injury, disease, and aging, in the absence of systemic mineral imbalance).
- •Significant gastrointestinal disorders that could interfere with absorption, metabolism, or excretion of pemigatinib.
- •Clinically significant or uncontrolled cardiac disease.
- •History or presence of an abnormal ECG, which, in the investigator's opinion, is clinically meaningful.
- •Chronic or current active infectious disease requiring systemic antibiotics or antifungal or antiviral treatment within 2 weeks prior to enrollment (participants with asymptomatic chronic infections on prophylactic treatment are allowed). Note: HIV-positive participants are allowed if all of the following criteria are met: CD4+ count ≥ 300/µL, undetectable viral load, receiving antiretroviral therapy that does not interact with study drug, and no HIV/AIDS-associated opportunistic infection in the last 12 months.
- •Use of any potent CYP3A4 inhibitors or inducers or moderate CYP3A4 inducers within 14 days or 5 half-lives (whichever is longer) before the first dose of study treatment. Note: Moderate CYP3A4 inhibitors are not prohibited
- •Known hypersensitivity or severe reaction to pemigatinib, gemcitabine, cisplatin, or their excipients.
- •Inadequate recovery from toxicity and/or complications from a major surgery before starting therapy.
研究组 & 干预措施
Gemcitabine + Cisplatin
Participants who experience disease progression while receiving gemcitabine + cisplatin or during the follow-up period and before starting a new anticancer therapy will be eligible to cross over and receive pemigatinib.
干预措施: Cisplatin (Drug)
Pemigatinib
干预措施: Pemigatinib (Drug)
Gemcitabine + Cisplatin
Participants who experience disease progression while receiving gemcitabine + cisplatin or during the follow-up period and before starting a new anticancer therapy will be eligible to cross over and receive pemigatinib.
干预措施: Gemcitabine (Drug)
结局指标
主要结局
Randomized Treatment Period: Progression-free Survival (PFS)
时间窗: up to 1422 days
PFS was defined as the time from the date of randomization until the date of disease progression (according to Response Evaluation Criteria in Solid Tumors version 1.1 \[RECIST v1.1\] and assessed by an Independent Central Review \[ICR\]) or death, whichever occurs first.
Randomized Treatment Period: Kaplan-Meier Estimates of PFS of the Indicated Lengths of Time
时间窗: up to 1422 days
PFS was defined as the time from the date of randomization until the date of disease progression (according to RECIST v1.1 and assessed by an ICR) or death, whichever occurs first. Kaplan-Meier estimates indicate the percent probability of a participant being alive at the indicated time after treatment start.
Transition Period: PFS
时间窗: up to 1496 days
PFS was defined as the time from the date of the first dose of study drug after transition until the earliest date of progressive disease or death due to any cause.
Transition Period: Kaplan-Meier Estimates of PFS of the Indicated Lengths of Time
时间窗: up to 1496 days
PFS was defined as the time from the date of the first dose of study drug after transition until the earliest date of progressive disease or death due to any cause. Kaplan-Meier estimates indicate the percent probability of a participant being alive at the indicated time after treatment start.
次要结局
- Randomized Treatment Period: Objective Response Rate (ORR)(up to 1422 days)
- Transition Period: ORR(up to 1496 days)
- Randomized Treatment Period: Overall Survival(up to 1422 days)
- Randomized Treatment Period: Kaplan-Meier Estimates of Overall Survival of the Indicated Lengths of Time(up to 1422 days)
- Randomized Treatment Period: Duration of Response (DOR)(up to 1422 days)
- Randomized Treatment Period: Kaplan-Meier Estimates of DOR of the Indicated Lengths of Time(up to 1422 days)
- Transition Period: DOR(up to 1496 days)
- Transition Period: Kaplan-Meier Estimates of DOR of the Indicated Lengths of Time(up to 1496 days)
- Randomized Treatment Period: Disease Control Rate (DCR)(up to 1422 days)
- Transition Period: DCR(up to 1496 days)
- Number of Participants With Any Treatment-emergent Adverse Event (TEAE)(up to 1457 days)
- Number of Participants With Any Treatment-related TEAE(up to 1457 days)
- Transition Period: Number of Participants With Any TEAE(up to 1531 days)
- Transition Period: Number of Participants With Any Treatment-related TEAE(up to 1531 days)
- Randomized Treatment Period: Change From Baseline (CFB) in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-30) Scores at Early Termination(Baseline; up to 1422 days)
- Randomized Treatment Period: Change From Baseline (CFB) in the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Including 21 Questions Specific to the Biliary System (EORTC QLQ-BIL21) at Early Termination(Baseline; up to 1422 days)
- Randomized Treatment Period: Number of Participants With the Indicated Responses on the European Quality of Life 5 Dimensions (3 Levels) Questionnaire (EQ-5D [3L])(Baseline; up to 1422 days)