A Phase 2 Basket Study of Tucatinib in Combination with Trastuzumab in Subjects with Previously Treated, Locally Advanced Unresectable or Metastatic Solid Tumors Driven by HER2 Alterations - Basket study of tucatinib and trastuzumab in solid tumors with HER2 alterations

Seagen Inc.0 个研究点目标入组 270 人开始时间: 2021年3月25日最近更新: 2024年4月15日

适应症

试验速览

阶段: 1 期
状态: 进行中（未招募）
发起方: Seagen Inc.
入组人数: 270

研究概览入排标准研究者记录与标识符相似试验

研究概览

简要总结

暂无简介。

研究设计

研究类型: Interventional clinical trial of medicinal product

入排标准

性别: All

入选标准

•1.Histologically or cytologically confirmed diagnosis of locally-advanced
•unresectable or metastatic solid tumor, including primary brain tumors
•2.Prior therapy:
•a. Subjects with non-squamous NSCLC: Must have progressed during or
•after standard treatment or for which no standard treatment is available
•b. Subjects with other disease types: Must have progressed during or after
•=1 prior line of systemic therapy for locally-advanced unresectable or
•metastatic disease
•Subjects with metastatic HR+ HER2-mutated breast cancer must have
•received a prior CDK4/6 inhibitor in the metastatic setting
•Subjects with metastatic cervical cancer must have received platinumbased
•chemotherapy with or without bevacizumab in the metastatic
•3.Progression during or after, or intolerance of, the most recent line of
•systemic therapy
•4.Disease demonstrating HER2 alterations (overexpression/amplification
•or HER2 activating mutations), as determined by local or central testing
•processed in a Clinical Laboratory Improvement Amendments (CLIA)- or
•International Organization for Standardization (ISO)-accredited
•laboratory, according to one of the following:
•a.HER2 overexpression/amplification from fresh or archival tumor tissue
•or blood utilizing one of the following tests, in subjects with tumor types
•other than breast cancer, GEC, or CRC:
•i.HER2 overexpression by immunohistochemistry (IHC): 3+ by breast or
•gastric algorithms
•ii.HER2 amplification by in situ hybridization (ISH) assay: fluorescence in
•situ hybridization (FISH) or chromogenic in situ hybridization (CISH)
•signal ratio =2.0 or gene copy number >6
•iii.HER2 amplification in tissue by next generation sequencing (NGS)
•iv.HER2 amplification in circulating tumor DNA (ctDNA) by blood-based
•b.Known activating HER2 mutations detected in fresh or archival tumor
•tissue or blood by NGS assay, including:
•Extracellular domain: G309A/E; S310F/Y; C311R/S; C334S
•Kinase domain: T733I; L755P/S; I767M; L768S; D769N/Y/H; Y772;
•A775; G776; V777L/M; G778; T798; L841V, V842I; N857S, T862A,
•L869R, H878Y, R896C, other exon 20 insertions
•Transmembrane/juxtamembrane domain: S653C, I655V; V659E;
•G660D; R678Q; V697.
•Subjects with HER2 activating mutations not listed above may be
•eligible, if supported by scientific literature and approved by the medical
•5.Have measurable disease per RECIST v1.1 criteria according to
•investigator assessment
•9.Have adequate hepatic function as defined by the following:
•a.Aspartate aminotransferase (AST) and alanine aminotransferase (ALT)
•=3 × upper limit of normal (ULN) (=5 × ULN if liver metastases are
•b.Total bilirubin =1.5 × ULN. Exception: subjects with known history of Gilbert's syndrome with direct bilirubin =1.5 × ULN and normal AST and
•ALT are eligible
•10.Have adequate baseline hematologic parameters as defined by:
•a.Absolute neutrophil count (ANC) =1.0 × 109/L
•b.Platelet count =100 × 109/L; subjects with stable platelet count from
•75 to 100 × 109/L may be included with approval from Medical Monitor
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排除标准

•1.Subjects with breast cancer, gastric or gastroesophageal junction
•adenocarcinoma, or CRC whose disease shows HER2
•amplification/overexpression.
•2.Previous treatment with HER2-directed therapy; subjects with uterine
•serous carcinoma or HER2-mutated gastric or gastroesophageal junction
•adenocarcinoma without HER2-overexpression/amplification may have
•received prior trastuzumab
•3.Known hypersensitivity to any component of the drug formulation of
•tucatinib or trastuzumab (drug substance, excipients, murine proteins),
•or any component of the drug formulation of fulvestrant in subjects with
•HR+ HER2-mutated breast cancer
•4.History of exposure to a >360 mg/m² doxorubicin-equivalent or >720
•mg/m² epirubicin-equivalent cumulative dose of anthracyclines
•5.Treatment with any systemic anti-cancer therapy, radiation therapy,
•major surgery, or experimental agent within =3 weeks of first dose of
•study treatment or are currently participating in another interventional
•clinical trial.
•6.Have any toxicity related to prior cancer therapies that has not
•resolved to = Grade 1, with the following exceptions:
•b.Congestive heart failure (CHF), which must have been = Grade 1 in
•severity at the time of occurrence, and must have resolved completely
•c.Anemia, which must have resolved to = Grade 2
•7.Have clinically significant cardiopulmonary disease such as:
•a.Ventricular arrhythmia requiring therapy
•b.Symptomatic hypertension or uncontrolled hypertension as determined
•by investigator
•c.Any history of symptomatic CHF
•d.Severe dyspnea at rest (National Cancer Institute Common
•Terminology Criteria for Adverse Events [NCI CTCAE] Grade 3 or above)
•due to complications of advanced malignancy
•e.Hypoxia requiring supplementary oxygen therapy except when oxygen
•therapy is needed only for obstructive sleep apnea
•8.Have known myocardial infarction or unstable angina within 6 months
•prior to first dose of study treatment
•9.Known to be positive for hepatitis B by surface antigen expression.
•Known to be positive for hepatitis C infection (positive by polymerase
•chain reaction). Subjects who have been treated for hepatitis C infection
•are permitted if they have documented sustained virologic response of
•10.Presence of known chronic liver disease
•11.Subjects known to be positive for human immunodeficiency virus
•(HIV) are excluded if they meet any of the following criteria:
•a.CD4+ T-cell count of <350 cells/µL
•b.Detectable HIV viral load
•c.History of an opportunistic infection within the past 12 months
•d.On stable antiretroviral therapy for <4 weeks
•12.Are pregnant, breastfeeding, or planning a pregnancy from time of
•informed consent until 7 months after the final dose of any study drug,
•and, if applicable, for at least 2 years after the final dose of fulvestrant
•13.Have inability to swallow pills
•14.Have used a strong cytochrome P450 (CYP) 2C8 inhibitor within 5
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研究者

发起方

Seagen Inc.

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