A Phase 1/2 Study of ARQ 087 in Adult Subjects With Advanced Solid Tumors With FGFR Genetic Alterations, Including Intrahepatic Cholangiocarcinoma With FGFR2 Gene Fusion
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 119
- 试验地点
- 12
- 主要终点
- Number of Patients With Drug-related Treatment-emergent Adverse Events (TEAEs)
研究概览
简要总结
This was an open-label, Phase 1/2, dose escalation and signal finding study of derazantinib administered to patients with advanced solid tumors (Part 1; Dose Escalation/Food-effect Cohorts) or with advanced solid tumors with FGFR genetic aberrations, including iCCA with FGFR2 gene fusion (Part 2; Expanded Cohort, signal finding).
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 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
- •Signed written informed consent granted
- •Men or women ≥18 years of age
- •Histologically or cytologically confirmed, locally advanced, inoperable, or metastatic solid tumors. Patients eligible for enrollment in the Expanded Cohort must have documented and/or confirmed FGFR genetic aberrations, including iCCA with FGFR2 gene fusion.
- •Failure to respond to standard therapy, or for whom standard therapy does not exist.
- •Evaluable or measurable disease
- •Archival and/or fresh biopsy tissue samples must be available prior to the first dose of the study drug
- •Life expectancy ≥ 12 weeks
- •Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
- •Hemoglobin (Hgb) ≥ 9.0 g/dL
- •Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L
- •Platelet count ≥ 100 x 10^9/L
- •Total bilirubin ≤ 1.5 × upper limit of normal (ULN) (≤ 2 x ULN for patients with cholangiocarcinoma)
- •Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3 × ULN (≤ 5 x ULN for patients with liver metastases)
- •Serum creatinine ≤ 1.5 x ULN or creatinine clearance > 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal
- •Albumin ≥ 2.8 g/dL
- •INR 0.8 to ULN or ≤ 3 for patients receiving anticoagulant therapy
- •Men or women of child-producing potential must agree to use double-barrier contraceptive measures, oral contraception, or avoid intercourse during the study and for 90 days after the last dose of study drug
- •Women of childbearing potential must have a negative serum pregnancy test during Screening Period and within 48 hours of the first dose of derazantinib.
排除标准
- •Anti-cancer therapy, such as chemotherapy, immunotherapy, hormonal, targeted therapy, or investigational agents within four weeks or five times of the drug half life, whichever is longer, of the first dose of derazantinib
- •Major surgery or radiation therapy within four weeks of the first dose of derazantinib
- •Previous treatment with FGFR inhibitors
- •History of allergic reactions attributed to compounds of similar chemical or biological composition as derazantinib
- •Unable or unwilling to swallow the complete daily dose of derazantinib
- •Clinically unstable central nervous system (CNS) metastasis
- •History of myocardial infarction (MI) or congestive heart failure defined as Class II to IV per the New York Heart Association classification within 6 months of the first dose of derazantinib (MI occurring >6 months of the first dose of derazantinib will be permitted)
- •Significant GI disorder(s) that could interfere with the absorption, metabolism, or excretion of derazantinib (e.g. Crohn's disease, ulcerative colitis, extensive gastric resection)
- •History and/or current evidence of clinically relevant ectopic mineralization/calcification
- •Previous malignancy within 2 years prior to the first dose of derazantinib, except curatively treated non-melanoma skin cancer, carcinoma in-situ of the breast or cervix, or superficial bladder tumors
- •Known human immunodeficiency virus (HIV) infection
- •Concurrent uncontrolled illness not related to cancer, including but not limited to:
- •Psychiatric illness/substance abuse/social situation that would limit compliance with study requirements.
- •Uncontrolled diabetes mellitus
- •Blood transfusion within 5 days of the blood draw being used to confirm eligibility
- •Pregnant or breastfeeding
研究组 & 干预措施
Low Dose Group
Patients who received derazantinib orally at dose levels from 25 mg every other day (QOD) - 200 mg daily (QD) on a 28-day schedule until documented progression of disease (clinical or radiological), unacceptable toxicity, or another of the discontinuation criteria.
干预措施: Derazantinib low dose range (Drug)
Middle Dose Group
Patients who received derazantinib orally at dose levels from 250 mg QD - 325 mg QD on a 28-day schedule until documented progression of disease (clinical or radiological), unacceptable toxicity, or another of the discontinuation criteria.
干预措施: Derazantinib middle dose range (Drug)
High Dose Group
Patients who received derazantinib orally at dose levels from 400 mg QD - 425 mg QD on a 28-day schedule until documented progression of disease (clinical or radiological), unacceptable toxicity, or another of the discontinuation criteria.
干预措施: Derazantinib high dose range (Drug)
Expanded Cohort Group
Patients who received derazantinib orally at the recommended phase 2 dose of 300 mg QD on a 28-day schedule until documented progression of disease (clinical or radiological), unacceptable toxicity, or another of the discontinuation criteria.
干预措施: Derazantinib at recommended phase 2 dose (RP2D) (Drug)
结局指标
主要结局
Number of Patients With Drug-related Treatment-emergent Adverse Events (TEAEs)
时间窗: Adverse events were collected and reported from the time of receiving first dose of derazantinib to the end of study assessment and follow-up period (30-day post-treatment)
Adverse events were graded for severity according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. CTCAE is classifying AEs and their associated severity from Grade 1 (Mild AE), Grade 2 (Moderate AE), Grade 3 (Severe or medically significant but not immediately life-threatening), Grade 4 (Life-threatening consequences) to Grade 5 (Death related to AE)
次要结局
- Proportion of Patients With an Objective Tumor Response Per RECIST 1.1(Assessments were performed at Baseline, and every 8 weeks during continuous drug administration until the End of Treatment visit (7 [+3] days after the last dose of derazantinib) or as otherwise clinically indicated.)
- Proportion of Patients With Disease Control Per RECIST 1.1(Assessments were performed at Baseline, and every 8 weeks during continuous drug administration until the End of Treatment visit (7 [+3] days after the last dose of derazantinib) or as otherwise clinically indicated.)
- Progression-free Survival (PFS)(Assessments were performed at Baseline, and every 8 weeks during continuous drug administration until the End of Treatment visit (7 [+3] days after the last dose of derazantinib) or as otherwise clinically indicated.)