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.

niversitair Medisch Centrum0 个研究点目标入组 10 人开始时间: 待定最近更新: 2024年4月9日

适应症

试验速览

阶段: 2 期
状态: 尚未招募
发起方
入组人数: 10

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

入排标准

年龄范围: 18 至 99（—）

入选标准

•1. Histologically or cytologically confirmed diagnosis of locally-advanced
•unresectable or metastatic solid tumor, including primary brain tumors
•2. Subjects with disease types other than breast cancer, biliary tract cancer,
•non-squamous NSCLC, and cervical cancer: Disease progression on or after the
•most recent systemic therapy for locally-advanced unresectable or metastatic
•3. Subjects with any breast cancer subtype:
•a. Must have HER2-mutated disease which does not display HER2
•overexpression/amplification
•b. Must have progressed on or after >=1 prior line of treatment (chemotherapy,
•endocrine therapy, or targeted therapy) for locally-advanced unresectable or
•metastatic breast cancer
•c. Subjects with metastatic HR+ HER2-mutated disease must have received a prior
•CDK4/6 inhibitor in the metastatic setting
•4. Subjects with biliary tract cancer: must have progressed on or after >=1
•prior line of treatment (chemotherapy, endocrine therapy, or targeted therapy)
•5. Subjects with non-squamous NSCLC: has relapsed from or is refractory to
•standard treatment or for which no standard treatment is available
•6. Subjects with cervical cancer:
•a. Subjects with metastatic cervical cancer must have progressed on or after >=1
•prior line of systemic therapy (platinum-based chemotherapy with or without
•bevacizumab) in the metastatic setting
•b. Subjects with locally advanced unresectable cervical cancer must have
•progressed on or after >=1 prior lines of systemic therapy
•7. 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 (3+ immunohistochemistry IHC) (breast or gastric
•algorithms)
•ii. HER2 amplification by in situ hybridization assay (fluorescence in situ
•hybridization [FISH] or chromogenic in situ hybridization signal ratio >=2.0 or
•gene copy number >6)
•iii. HER2 amplification in tissue by next generation sequencing (NGS) assay
•iv. HER2 amplification in circulating tumor DNA (ctDNA) by blood-based NGS assay
•b. Known activating HER2 mutations detected in fresh or archival tumor tissue
•or blood by NGS assay, including:
•o Extracellular domain: G309A/E; S310F/Y; C311R/S; C334S
•o Kinase domain: T733I; L755P/S; I767M; L768S; D769N/Y/H; Y772; A775; G776;
•V777L/M; G778; T798; L841V, V842I; N857S, T862A, L869R, H878Y, R896C
•o Transmembrane/juxtamembrane domain: S653C, I655V; V659E; G660D; R678Q; V697.
•o Subjects with HER2 activating mutations not listed above may be eligible, if
•supported by scientific literature and approved by the medical monitor
•8. Have measurable disease per RECIST v1.1 criteria according to investigator
•9. Be at least 18 years of age at time of consent, or considered an adult by
•local regulations
•10. Have Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
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排除标准

•1. Subjects with breast cancer, GEC, or CRC whose disease shows HER2
•amplification/overexpression.
•2. Previous treatment with HER2-directed therapy; subjects with uterine serous
•carcinoma 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
•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, 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:
•a. Alopecia
•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 12 weeks
•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:
•CD4+ T-cell count of <350 cells/µL
•Detectable HIV viral load
•History of an opportunistic infection within the past 12 months
•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 half-lives
•of the inhibitor, or have used a strong CYP3A4 or CYP2C8 inducer within 5 days
•prior to start of treatment
•15. Have any other medical, social, or psychosocial factors that, in the
•opinion of the investigator, could impact safety or compliance with study
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研究者

发起方

niversitair Medisch Centrum

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