💬In plain words
What the trial is, and whether it could suit you
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).
Sign in to get the eligibility rules as simple questions to take to your doctor.
📋 Eligibility rules (as published)
Inclusion criteria:
1. Male or female, aged ≥18 years.
2. Histologically or cytologically confirmed NSCLC with EGFR sensitizing mutations (including L858R or Exon 19Del), ineligible for curative surgery or radiotherapy.
3. CNS metastases diagnosed as brain metastases (BM) and/or leptomeningeal metastases (LM) by imaging and/or cerebrospinal fluid pathological examination.
4. Planning to receive zorifertinib (zorifertinib group) or other anti-tumor treatments (other treatment group) as first-line treatment.
5. Voluntarily agreeing to participate in this study and signing the informed consent form.
Exclusion criteria:
1. 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).
2. 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:
1. . No prior treatment with chemotherapy, EGFR-TKIs, biological therapy, immunotherapy, or any investigational drug that is considered first line treatment for advanced NSCLC.
2. . Eligible patients are not candidates for definitive surgical resection or radiation of all lesions in the opinion of the treating physician.
3. . 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.
4. . Patients may have prior placement of a properly functioning CNS shunt or Ommaya reservoir.
5. . ECOG performance status 0 or 1, with no deterioration over the past 2 weeks, and expected survival time ≥ 3 months.
6. . 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.
7. . 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:
1. . 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).
2. . Positive for T790M mutation documented by central or local laboratory using an approved or validated test method, or documented positive KRAS or cMET.
3. . Patients who have received any investigational drug, biological therapy, or immunotherapy for their malignant tumors within the past 21 days.
4. . 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.
5. . Presence of only leptomeningeal metastases (LM) disease confirmed by MRI and/or positive cerebrospinal fluid (CSF) pathology, with no brain metastases (BM).
6. . Prior radiation therapy for CNS metastases that involves measurable or non-measurable sites of disease to assess efficacy.
7. . Patients who have received radiation to more than 30% of the bone marrow within 2 weeks before the first dose of study treatment.
8. . 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).
9. . Unmanageable nausea and vomiting, chronic gastrointestinal diseases, or prior gastric resection or surgical procedure that may interfere with adequate absorption of study drug.
10. . 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.
11. . History of any type of documented interstitial lung disease or radiation pneumonitis.
12. . 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.
13. . Women who are pregnant or lactating. WOCBP and fertile men with a WOCBP-partner not using adequate contraception measures.
14. . 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.
15. . 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,
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