A Phase 1b/2, Multicenter, Open-label Basket Study Evaluating the Safety and Efficacy of Bemarituzumab Monotherapy in Solid Tumors With FGFR2b Overexpression (FORTITUDE-301)
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- Amgen
- 入组人数
- 260
- 试验地点
- 195
- 主要终点
- Part 1: Number of Participants Who Experience a Dose Limiting Toxicity (DLT)
研究概览
简要总结
The primary objectives of this study are to observe the safety and tolerability of bemarituzumab and to evaluate preliminary antitumor activity.
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 99 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥ 18 years (or legal adult age within country, whichever is older) at the time that the Informed Consent Form (ICF) is signed
- •Histologically or cytologically confirmed cancer of one of the following types, refractory to or relapsed after at least 1 prior standard therapeutic regimen in the advanced/metastatic setting, as specified below. If no standard of care therapies exist for the participant, or the participant cannot tolerate or refuses standard of care anticancer therapy, the participant may be allowed to participate on the study after discussion between the investigator and Amgen medical monitor. Participants who have not received all approved or standard treatments for their cancer must be informed that these alternatives to receiving bemarituzumab are available prior to consenting to participate in the trial.
- •head and neck squamous cell carcinoma: ≥ 1 line of therapy
- •triple-negative breast cancer: ≥ 2 lines of therapy
- •Intrahepatic cholangiocarcinoma ≥ 1 line of therapy
- •lung adenocarcinoma: at least platinum-based chemotherapy, checkpoint inhibitor, and targeted therapy
- •platinum resistant ovarian epithelial cell carcinoma, including fallopian tube cancers and primary peritoneal cancers, defined as progression during or within 6 months of a platinum containing regimen: ≥ 1 line of therapy
- •endometrial adenocarcinoma: ≥ 1 line of therapy
- •cervical carcinoma: ≥ 1 line of therapy
- •other solid tumors: ≥ 1 line of therapy
- •Disease that is unresectable, locally advanced, or metastatic (not amenable to curative therapy)
- •Tumor overexpresses FGFR2b as determined by centrally performed immunohistochemistry (IHC) testing
- •Measurable disease per Response Evaluation Criteria in Solid Tumors Version 1.1
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- •Adequate organ function as determined per protocol.
排除标准
- •Untreated or symptomatic central nervous system (CNS) metastases or leptomeningeal disease.
- •Other solid tumor cohort excludes primary tumors of the CNS, squamous non-small cell lung cancer, gastric adenocarcinoma, and gastroesophageal junction adenocarcinoma
- •Impaired cardiac function or clinically significant cardiac disease including: unstable angina within 6 months prior to first dose of study treatment, acute myocardial infarction ≥ 6 months prior to first dose of study treatment, New York Heart Association (NYHA) class II-IV congestive heart failure, uncontrolled hypertension (defined as an average systolic blood pressure ≥ 160 mmHg or diastolic ≥ 100 mmHg despite optimal treatment, uncontrolled cardiac arrhythmias requiring anti-arrhythmic therapy other than beta blockers or digoxin, active coronary artery disease or corrected QT interval QTc ≥ 470
- •History of systemic disease or ophthalmologic disorders requiring chronic use of ophthalmic steroids
- •Evidence of any ongoing ophthalmologic abnormalities or symptoms that are acute (within 4 weeks) or actively progressing
- •Unwillingness to avoid use of contact lenses during study treatment and for at least 100 days after the end of treatment
- •Recent (within 6 months) corneal surgery or ophthalmic laser treatment or recent (within 6 months) history of, or evidence of, corneal defects, corneal ulcerations, keratitis, or keratoconus, or other known abnormalities of the cornea that may pose an increased risk of developing a corneal ulcer prior/concomitant therapy
- •Prior treatment with any investigational selective inhibitor of the fibroblast growth factor (FGF)/FGF receptor pathway (unless approved standard of care for tumor indication).
研究组 & 干预措施
Part 2: Monotherapy Dose Expansion
Participants across multiple primary epithelial solid tumors with centrally determined FGFR2b overexpression and relapsed/refractory unresectable and/or metastatic disease will receive the dose of bemarituzumab identified as the recommended Phase 2 dose during Part 1.
干预措施: Bemarituzumab (Drug)
Part 1: Monotherapy Dose Exploration
Participants across multiple primary epithelial solid tumors with centrally determined FGFR2b overexpression and relapsed/refractory unresectable and/or metastatic disease will receive 1 of 2 dose regimens of bemarituzumab to determine recommended Phase 2 dose.
干预措施: Bemarituzumab (Drug)
结局指标
主要结局
Part 1: Number of Participants Who Experience a Dose Limiting Toxicity (DLT)
时间窗: Day 1 to Day 28
Part 1: Number of Participants Who Experience a Treatment-emergent Adverse Event (TEAE)
时间窗: Day 1 to 28 days after last dose (a maximum of 2 years)
Adverse events (AEs) are defined as any untoward medical occurrence in a clinical study participant irrespective of a causal relationship with the study treatment. TEAEs are any event that occurs after the participant has received study treatment. Any clinically significant changes in vital signs, visual acuity, and clinical laboratory tests that occur after study treatment administration will be recorded as TEAEs.
Part 1: Number of Participants Who Experience a Treatment-related Adverse Event
时间窗: Day 1 to 28 days after last dose (a maximum of 2 years)
Part 2: Objective Response (OR) Rate
时间窗: Up to approximately 2 years
OR = complete response (CR) + partial response (PR), measured by computed tomography (CT) or magnetic resonance imaging (MRI) as determined by investigator per Response Evaluation Criteria in Solid Tumors (RECIST v1.1).
次要结局
- Part 1: OR Rate(Up to approximately 2 years)
- Parts 1 and 2: Disease Control (DC) Rate(Up to approximately 2 years)
- Parts 1 and 2: Duration of Response (DOR)(Up to approximately 2 years)
- Parts 1 and 2: Time to Response(Up to approximately 2 years)
- Parts 1 and 2: Progression-free Survival (PFS)(Up to approximately 2 years)
- Parts 1 and 2: Overall Survival (OS)(Up to approximately 2 years)
- Part 2: Number of Participants Who Experience a TEAE(Day 1 to 28 days after last dose (a maximum of 2 years))
- Part 2: Number of Participants Who Experience a Treatment-related AE(Day 1 to 28 days after last dose (a maximum of 2 years))
- Parts 1 and 2: Area Under the Concentration Time Curve (AUC) of Bemarituzumab(Day 1 to 28 days after last dose (a maximum of 2 years))
- Parts 1 and 2: Maximum Observed Serum Concentration (Cmax) of Bemarituzumab(Day 1 to 28 days after last dose (a maximum of 2 years))
- Parts 1 and 2: Observed Concentration at the End of a Dose Interval (Ctrough) of Bemarituzumab(Day 1 to 28 days after last dose (a maximum of 2 years))