NCT07143045招募中不适用
A Prospective Cohort Study of Zorifertinib as a First-line Treatment in Patients With Epidermal Growth Factor Receptor-mutant Advanced Non-small Cell Lung Cancer With Central Nervous System (CNS) Metastases
Alpha Biopharma (Jiangsu) Co., Ltd.34 个研究点 分布在 1 个国家目标入组 800 人开始时间: 2025年12月29日最近更新:
干预措施
相关药物
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 800
- 试验地点
- 34
- 主要终点
- Overall Survival (OS)
研究概览
简要总结
This study is a patient-centered, two-group, three-cohort, multi-center, prospective study to further evaluate the survival benefits and safety of zorifertinib as a first-line treatment in EGFRm+ advanced NSCLC patients with CNS metastases, and to compare the clinical value of zorifertinib with other epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs).
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
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
- •Male or female, aged ≥18 years.
- •Histologically or cytologically confirmed NSCLC with EGFR sensitizing mutations (including L858R or Exon 19Del), ineligible for curative surgery or radiotherapy.
- •CNS metastases diagnosed as brain metastases (BM) and/or leptomeningeal metastases (LM) by imaging and/or cerebrospinal fluid pathological examination.
- •Planning to receive zorifertinib (zorifertinib group) or other anti-tumor treatments (other treatment group) as first-line treatment.
- •Voluntarily agreeing to participate in this study and signing the informed consent form.
排除标准
- •Currently participating or planning to participate in any interventional clinical study for first-line treatment (patients who have participated in non-interventional, real-world studies may still be included).
- •Other reasons that, in the Investigator's opinion, make the patient unsuitable for this study.
- •For patients in Cohort A of the zorifertinib group, the following inclusion/exclusion criteria of the EVEREST study must also be met:
- •Inclusion Criteria A:
- •. No prior treatment with chemotherapy, EGFR-TKIs, biological therapy, immunotherapy, or any investigational drug that is considered first line treatment for advanced NSCLC.
- •. Eligible patients are not candidates for definitive surgical resection or radiation of all lesions in the opinion of the treating physician.
- •. All patients must be stable without any systemic (oral or parenteral) corticosteroid or anticonvulsant therapy for at least 2 weeks prior to study treatment. Inhaled non-absorbable and topical corticosteroid use are permitted as indicated.
- •. Patients may have prior placement of a properly functioning CNS shunt or Ommaya reservoir.
- •. ECOG performance status 0 or 1, with no deterioration over the past 2 weeks, and expected survival time ≥ 3 months.
- •. Women of child-bearing potential (WOCBP) and male patients should agree to take medically acceptable contraception measures while on study treatment and for 3 months following completion of study treatment. All WOCBP must have a negative pregnancy test at screening.
- •. Patients with measurable CNS lesions must have at least one site of CNS lesion, which has not been previously irradiated, can be accurately measured at baseline as ≥ 10 mm in the longest diameter by MRI, and is suitable for accurate repeated measurements. Measurable extracranial lesions are not required. Patients with non-measurable CNS lesions must have at least one extracranial lesion, which has not been previously irradiated, can be accurately measured at baseline as ≥ 10 mm in the longest diameter (except for lymph nodes which must have a short diameter ≥ 15 mm) by CT/MRI, and is suitable for accurate repeated measurements.
- •Exclusion Criteria A:
- •. Prior treatment with EGFR-TKIs (if EGFR-TKIs were used as adjuvant therapy, patients may be enrolled if the time from discontinuation to relapse meets the following requirements: >6 months for Cohort A, and >3 months for Cohorts B and C).
- •. Positive for T790M mutation documented by central or local laboratory using an approved or validated test method, or documented positive KRAS or cMET.
- •. Patients who have received any investigational drug, biological therapy, or immunotherapy for their malignant tumors within the past 21 days.
- •. Patients who have had a major surgical procedure (excluding the need for placement of vascular access or a CNS shunt), or significant traumatic injury within 4 weeks of the first dose of study treatment, or have an anticipated need for major surgery during the study.
- •. Presence of only leptomeningeal metastases (LM) disease confirmed by MRI and/or positive cerebrospinal fluid (CSF) pathology, with no brain metastases (BM).
- •. Prior radiation therapy for CNS metastases that involves measurable or non-measurable sites of disease to assess efficacy.
- •. Patients who have received radiation to more than 30% of the bone marrow within 2 weeks before the first dose of study treatment.
- •. Patients currently receiving (or unable to stop use at least 1 week prior to receiving the first dose of study treatment) certain medications or herbal supplements that are known to be potent inhibitors or inducers of CYP3A4/5 (see Appendix A).
- •. Unmanageable nausea and vomiting, chronic gastrointestinal diseases, or prior gastric resection or surgical procedure that may interfere with adequate absorption of study drug.
- •. History of concurrent and/or other active malignant tumors requiring treatment within 5 years of study treatment, excluding prior treated squamous cell carcinoma or basal cell carcinoma or carcinoma in situ.
- •. History of any type of documented interstitial lung disease or radiation pneumonitis.
- •. Presence of any severe or uncontrolled systemic disease or condition, including: (i) uncontrolled hypertension or diabetes; (ii) serious cardiac, pulmonary or renal disorders; (iii) active bleeding diatheses; (iv) any active type of bacterial, viral, fungal or other infection that would pose a significant risk to the patient in the opinion of the Investigator; or (v) active hepatitis B virus positive (defined as hepatitis B surface antigen (HBsAg) positive or hepatitis B core antibody (HBcAb) positive, and hepatitis B DNA positive (or detectable) or above the cut-off value) or positive HCV antibodies or positive HIV test result.
- •. Women who are pregnant or lactating. WOCBP and fertile men with a WOCBP-partner not using adequate contraception measures.
- •. Patients with unstable and symptomatic metastases: Any unstable and symptomatic CNS or distant metastasis that is not symptomatically controlled by prior surgery, radiotherapy or corticosteroid therapy within 2 weeks of initial study treatment.
- •. Any unresolved toxicities from prior therapy, greater than Common Terminology Criteria for Adverse Events (CTCAE 5.0) Grade 1 at the time of starting study treatment, with exception of alopecia.
- •. Patients with a significant cardiovascular disorder or condition, including any of the following:
- •Congestive heart failure (CHF) currently requiring treatment and patients with New York Heart Association (NYHA) Class III/IV CHF (see Appendix B).
- •Need for antiarrhythmic drug therapy for a ventricular arrhythmia or patients with uncontrolled or unstable arrhythmias.
- •Severe conduction disturbance (e.g., second- or third-degree AV block).
- •Angina pectoris requiring treatment.
- •QTc interval > 450 msec (males) or > 470 msec (females).
- •History of congenital long QT syndrome, congenital short QT syndrome, Torsades de Pointes, or Wolff Parkinson White syndrome.
- •Left ventricular ejection fraction (LVEF) <50% as determined by echocardiography or MUGA scan.
- •Myocardial infarction diagnosed within the past 6 months.
- •. Inadequate bone marrow reserve or organ function as demonstrated by any of the following laboratory values:
- •Absolute neutrophil count <1.5 × 109/L.
- •Platelet count <100 × 109/L (Transfusion-dependent patients are excluded from this study).
- •Hemoglobin <90 g/L.
- •Alanine aminotransferase (ALT) > 2.5 times the upper limit of normal (ULN) in the absence of documented metastases to liver or > 5 times the ULN in the presence of metastases to liver.
- •Aspartate aminotransferase (AST) > 2.5 times the ULN in the absence of documented metastases to liver or > 5 times the ULN in the presence of metastases to liver.
- •Total bilirubin > 1.5 times the ULN in the absence of metastases to liver or >3 times the ULN in the presence of documented Gilbert's syndrome (unconjugated hyperbilirubinemia) or metastases to liver.
- •Creatinine >1.5 times the ULN concurrent with creatinine clearance <50 mL/min (measured or calculated by Cockcroft-Gault equation). Confirmation of creatinine clearance is only required when creatinine is >1.5 times the ULN.
- •If bone metastases are present and liver function is otherwise considered adequate by the Investigator, then isolated elevated alkaline phosphatase (ALP) is not an exclusion criterion.
- •. History of hypersensitivity to active or inactive excipients of the study drug or drugs with a similar chemical structure or class to the study drug.
- •. Judgment by the Investigator that the patient should not participate in the study if the patient is unwilling to comply with all study procedures and treatment.
- •. History of recent stroke (<6 months), or prior central nervous system injury that has persistent neurologic deficits that would affect neurologic assessments.
- •. Significant medical or psychiatric illness that would interfere with the compliance to the protocol and ability to tolerate treatment.
- •. Patients who have received any anti-neoplastic herbal medicines for their malignant tumors within the past 2 weeks.
研究组 & 干预措施
Cohort A
Patients who receive first-line zorifertinib and meet the inclusion/exclusion criteria of the EVEREST study (the EVEREST study is a randomized, open-label, multi-center, Phase II/III study to compare the efficacy and safety of first-line zorifertinib versus gefitinib/erlotinib in EGFR-mutant advanced NSCLC patients with CNS metastases)
干预措施: zorifertinib (Drug)
Cohort B
Patients who receive first-line zorifertinib but do not meet the inclusion/exclusion criteria of the EVEREST study (the EVEREST study is a randomized, open-label, multi-center, Phase II/III study to compare the efficacy and safety of first-line zorifertinib versus gefitinib/erlotinib in EGFR-mutant advanced NSCLC patients with CNS metastases)
干预措施: zorifertinib (Drug)
Cohort C
Patients who receive various other anti-tumor drugs selected by the clinician, excluding zorifertinib, as first-line treatment.
结局指标
主要结局
Overall Survival (OS)
时间窗: up to 36 months
The period from the first administration date of the study treatment to the date of death due to any cause.
次要结局
- Incidence of Adverse Events (AEs) for zorifertinib(up to 36 months)
- Incidence of Dose Adjustments for zorifertinib(up to 36 months)
- Progression-free survival (PFS)(every 8 weeks,up to 36 months)
- intracranial Progression-free survival (iPFS)(every 8 weeks,up to 36 months)
- Objective Response Rate (ORR)(every 8 weeks, up to 36 months)
研究者
研究点 (34)
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