FIGHT: A Phase 2 Randomized, Double-Blind, Controlled Study Evaluating Bemarituzumab (FPA144) and Modified FOLFOX6 in Patients With Previously Untreated Advanced Gastric and Gastroesophageal Junction Cancer: Phase 2 Preceded by Dose-Finding in Phase 1
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 155
- 试验地点
- 189
- 主要终点
- Progression-Free Survival (PFS)
研究概览
简要总结
The main objective of the Phase 2 part of the study is to evaluate the efficacy of bemarituzumab (FPA144), a targeted antibody, in combination with modified FOLFOX6 compared to placebo in combination with modified FOLFOX6 in participants with advanced gastrointestinal cancer.
详细描述
Study FPA144-004 is a phase 1/2, multicenter, global, double-blind, randomized, controlled study designed to evaluate the safety, tolerability, efficacy, and pharmacokinetics (PK) of bemarituzumab in combination with mFOLFOX6, compared with placebo in combination with mFOLFOX6, in adults with unresectable, locally advanced, or metastatic gastric cancer including cancer of the gastroesophageal junction (GEJ).
This study includes a Phase 1 safety run-in portion and a Phase 2 portion. The Phase 1 safety run-in is an open-label dose-escalation of bemarituzumab + mFOLFOX6 in patients with GI tumors (not FGFR2 selected) that is reported separately (NCT03343301).
The Phase 2 portion of the study (to follow the Phase 1 safety run-in) is described in this record.
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
- Double (Participant, Investigator)
盲法说明
Double blinded (participant, treating physician)
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 gastric or gastroesophageal junctional adenocarcinoma (not amenable to curative therapy)
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
- •Adequate hematological, liver and kidney function. Measurable or non-measurable, but evaluable disease using RECIST v1.1
- •Fibroblast growth factor receptor 2b (FGFR2b) overexpression as determined by a centrally performed immunohistochemistry tissue test and/or FGFR2 gene amplification as determined by a centrally performed circulating tumor deoxyribonucleic acid (ctDNA) blood based assay
- •Candidate for mFOLFOX6 chemotherapy
排除标准
- •Untreated or symptomatic central nervous system (CNS) metastases
- •Clinically significant cardiac disease,
- •Peripheral sensory neuropathy >/= Common Terminology Criteria for Adverse Events (CTCAE) Grade 2
- •Active infection requiring systemic treatment
- •Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness, or known active or chronic hepatitis B or C infection
- •Prior treatment with any selective inhibitor of the fibroblast growth factor (FGF)-FGFR pathway
- •Known abnormalities of the cornea that may pose an increased risk of developing a corneal ulcer
- •Known positivity for human epidermal growth factor receptor 2 (HER2)
- •Women who are pregnant or breastfeeding
- •Note: Other protocol defined Inclusion/Exclusion criteria may apply
研究组 & 干预措施
Bemarituzumab + mFOLFOX6
Participants received 15 mg/kg bemarituzumab administered every 2 weeks (Q2W) with a single additional bemarituzumab 7.5 mg/kg dose on cycle 1 day 8. Participants also received mFOLFOX6 chemotherapy administered Q2W. Treatment continued until unacceptable toxicity, disease progression, or death.
干预措施: Bemarituzumab (Biological)
Bemarituzumab + mFOLFOX6
Participants received 15 mg/kg bemarituzumab administered every 2 weeks (Q2W) with a single additional bemarituzumab 7.5 mg/kg dose on cycle 1 day 8. Participants also received mFOLFOX6 chemotherapy administered Q2W. Treatment continued until unacceptable toxicity, disease progression, or death.
干预措施: Modified FOLFOX6 (Drug)
Placebo + mFOLFOX6
Participants received placebo for bemarituzumab administered every 2 weeks with a single additional placebo dose on cycle 1 day 8. Participants also received mFOLFOX6 chemotherapy administered Q2W. Treatment continued until unacceptable toxicity, disease progression, or death.
干预措施: Placebo (Drug)
Placebo + mFOLFOX6
Participants received placebo for bemarituzumab administered every 2 weeks with a single additional placebo dose on cycle 1 day 8. Participants also received mFOLFOX6 chemotherapy administered Q2W. Treatment continued until unacceptable toxicity, disease progression, or death.
干预措施: Modified FOLFOX6 (Drug)
结局指标
主要结局
Progression-Free Survival (PFS)
时间窗: From randomization until the primary analysis data cut-off date of 23 September 2020; median time on follow-up was 10.9 months.
PFS was defined as time from randomization until the date of radiographic disease progression based on investigator assessment using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 or death from any cause, whichever came first. PFS was analyzed using Kaplan-Meier methods. Participants with no progression or death, or who started new anticancer therapy before documented progression or death without documented progression, or who had ≥ 2 consecutive missing tumor assessments before documented progression or death without documented progression were censored on the date of last adequate tumor assessment. Participants with no baseline tumor assessment, were censored at the date of randomization. The primary efficacy analysis was pre-specified to be conducted after at least 84 PFS events were observed.
次要结局
- Overall Survival (OS)(From randomization until the primary analysis data cut-off date of 23 September 2020; median time on follow-up was 10.9 months.)
- Number of Participants With Treatment-emergent Adverse Events (TEAEs)(From first dose of study drug to 28 days after last dose of study drug. Actual median (min, max) duration of treatment emergent period was 29 (4.1, 157) weeks in the bemarituzumab + mFOLFOX6 group and 28 (4.3, 133) weeks in the placebo + mFOLFOX6 group.)
- Overall Response Rate (ORR)(Tumor assessments were performed every 8 weeks until 12 months and then every 12 weeks thereafter until disease progression or additional anticancer therapy was initiated; the median duration of follow-up time was 10.9 months.)