CRESTONE: A Phase 2 Study of Seribantumab in Adult Patients With Neuregulin-1 (NRG1) Fusion Positive Locally Advanced or Metastatic Solid Tumors
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 75
- 试验地点
- 42
- 主要终点
- Objective Response Rate
研究概览
简要总结
This study is an open-label, international, multi-center, Phase 2 study in adult patients with recurrent, locally-advanced or metastatic solid tumors, which harbor the NRG1 gene fusion.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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
- •To be eligible for participation in the study, patients must meet the following inclusion criteria:
- •Locally-advanced or metastatic solid tumor with an NRG1 gene fusion identified through molecular assays, such as PCR, NGS (RNA or DNA) or FISH, by a CLIA-certified or similarly accredited laboratory
- •Availability of fresh or archived FFPE tumor sample to be submitted to a central laboratory for confirmation of NRG1 gene fusion status
- •Patients should have received a minimum of one prior standard therapy appropriate for their tumor type and stage of disease, progressed or been nonresponsive to these available therapies, with no further available curative therapy options
- •≥ 18 years of age
- •ECOG performance status (PS) 0, 1 or 2
- •Patients must have at least one measurable extra-cranial lesion as defined by RECIST v1.1
- •Adequate hepatic function defined as:
- •Serum AST and serum ALT < 2.5 × upper limit of normal (ULN), or AST and ALT < 5 × ULN if liver function abnormalities due to underlying malignancy
- •Total bilirubin < 2.0 ULN. Subjects with a known history of Gilberts Disease and an isolated elevation of indirect bilirubin are eligible
- •Adequate hematologic status, defined as:
- •Absolute neutrophil count (ANC) ≥1.5 × 109/L not requiring growth factor support for at least 7 days prior to Screening, and
- •Platelet count ≥100.0×109/L not requiring transfusion support for at least 7 days prior to Screening
- •Able to provide informed consent or have a legal representative able and willing to do so
- •Ability to comply with outpatient treatment, laboratory monitoring, and required clinic visits for the duration of study participation
- •Willingness of men and women of reproductive potential to observe conventional and effective birth control for the duration of treatment and for 3 months following study completion; this may include barrier methods such as condom or diaphragm with spermicidal gel.
排除标准
- •Known, actionable oncogenic driver mutation other than NRG1 fusion where available standard therapy is indicated
- •Life expectancy < 3 months
- •Pregnant or lactating
- •Prior treatment with ERBB3/HER3 directed therapy (Cohort 1 only)
- •Prior treatment with pan-ERBB or any ERBB/HER2/HER3 directed therapy (Cohort 1 only)
- •Symptomatic or untreated brain metastases (Note: Patients with asymptomatic brain metastases treated with radiation or surgery and without evidence of progression by imaging at screening are eligible to participate in the study. Patients requiring ongoing corticosteroids to treat brain metastases will not be eligible).
- •Received other investigational agent or anticancer therapy within 28 days prior to planned start of seribantumab or 5 half-lives, whichever is shorter
- •Prior to initiation of seribantumab treatment, patients must have recovered from clinically significant toxicities from prior anticancer or investigational therapy
- •Any other active malignancy requiring systemic therapy
- •Known hypersensitivity to any of the components of seribantumab or previous CTCAE grade 3 or higher hypersensitivity reactions to fully human monoclonal antibodies
- •Clinically significant cardiac disease, including symptomatic congestive heart failure, unstable angina, acute myocardial infarction within 12 months of planned first dose, or unstable cardiac arrhythmia requiring therapy (including torsades de pointes)
- •Active uncontrolled systemic bacterial, viral, or fungal infection
- •Patients who are not appropriate candidates for participation in this clinical study for any other reason as deemed by the investigator
研究组 & 干预措施
Cohort 1
A minimum of 55 adult advanced solid tumor patients harboring NRG1 gene fusions, who have received prior standard treatment, excluding prior ERBB-directed therapy.
Seribantumab 1-h IV infusion at various doses once weekly, every 2 weeks and every 3 weeks, during the induction, consolidation and maintenance dosing phases, respectively.
干预措施: Seribantumab (Drug)
Cohort 2
Up to 10 adult advanced solid tumor patients harboring NRG1 gene fusions, who have received prior standard treatment, including prior ERBB-directed therapy.
Seribantumab 1-h IV infusion at various doses once weekly, every 2 weeks and every 3 weeks, during the induction, consolidation and maintenance dosing phases, respectively.
干预措施: Seribantumab (Drug)
Cohort 3
Up to 10 adult advanced solid tumor patients harboring NRG1 gene fusions lacking an EGF-like domain, who have received prior standard treatment, which may have included prior ERBB-directed therapy.
Seribantumab 1-h IV infusion at various doses once weekly, every 2 weeks and every 3 weeks, during the induction, consolidation and maintenance dosing phases, respectively.
干预措施: Seribantumab (Drug)
结局指标
主要结局
Objective Response Rate
时间窗: Up to 12 months
Tumor assessments were evaluated at baseline by computerized tomography (CT) or magnetic resonance imaging (MRI). The primary objective of this study was to determine the overall objective response rate (ORR) per investigator assessment, defined as confirmed complete response (CR; disappearance of all target lesions) + partial response (PR; at least a 30% decrease in the sum of the longest diameter of target lesions) by RECIST v1.1, for seribantumab monotherapy (3,000 mg QW) in patients with centrally confirmed NRG1 fusion.
次要结局
未报告次要终点