Non-small cell lung cancer patients with brain parenchymal metastasis (except meningeal metastasis) diagnosed by imaging after disease progression during first-line treatment with third-generation EGFR-TKIs (single agent or combination)
Conditions
Interventions
Intervention group:Zorifertinib combination with Sacituzumab Tirumotecan
Sponsors
Shanghai Pulmonary Hospital
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: 1.The subject has fully understood the study and voluntarily signed the Written Informed Consent Form (ICF). 2.Aged 18 to 75 years (inclusive) at the time of signing the ICF. 3.Histologically or cytologically confirmed NSCLC with documented EGFR-sensitive mutations (including L858R and/or Exon 19 Del). 4.Radiographically confirmed brain parenchymal metastases. Patients may have concurrent leptomeningeal metastases (LM); however, those with LM only, spinal cord compression, or extensive LM are excluded. 5.Disease progression following first-line treatment with a third-generation EGFR-TKI (either as monotherapy or in combination), including patients who failed adjuvant therapy (progression during adjuvant therapy or within 6 months after treatment discontinuation). 6.Must have at least one reproducible and evaluable target lesion (intracranial and/or extracranial) according to RECIST v1.1. Previously irradiated lesions cannot be considered target lesions unless radiographic evidence shows clear progression of the lesion. 7.For subjects with neurological symptoms, the symptoms must be stable, requiring no increase in corticosteroid dosage for at least 1 week prior to the start of study treatment to maintain CNS symptom control. 8.All toxicities related to prior anti-tumor therapies (including radiotherapy) must have recovered to CTCAE v5.0 grade = 1.5 x 10^9/L (2) Platelet count >= 100 x 10^9/L (3) Hemoglobin >=90 g/L (4) Serum creatinine = 50 mL/min (5) Total bilirubin = 3 months. 11. ECOG performance status <= 1.
Exclusion criteria
Exclusion criteria: 1.Have a history of radiotherapy within 28 days prior to study drug administration, or palliative radiotherapy to bone occurring within 14 days prior to study drug administration. 2.Have undergone major surgery (e.g., intrathoracic, intra-abdominal, or intrapelvic surgery) within 4 weeks prior to the first dose of study treatment, or have not recovered from the side effects of such surgery. 3.Have other active malignancies currently requiring treatment, besides NSCLC. 4.Have clinically significant, uncontrolled heart disease and/or a cardiac-related event within the past 6 months, such as: (1) Myocardial infarction or documented history of heart failure (NYHA Class III-IV) within 6 months prior to screening; (2) Uncontrolled hypertension: systolic blood pressure >=160 mmHg and/or diastolic blood pressure >=100 mmHg, with or without antihypertensive medication; adjustment of antihypertensive medication before screening is permitted; (3) Arrhythmias not controlled by medication; (4) QTcF >470 ms at screening; (5) Left ventricular ejection fraction (LVEF) <50%. 5.Have gastrointestinal diseases or severely impaired gastrointestinal function that may significantly affect drug absorption (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, or malabsorption syndrome). 6.Have a documented history of severe dry eye syndrome, severe meibomian gland disease and/or blepharitis, or severe corneal disease that impedes/delays corneal healing. 7.Have clinically severe pulmonary impairment due to concomitant lung diseases, including but not limited to any underlying lung disease (e.g., severe asthma within 3 months prior to the first dose, severe COPD, restrictive lung disease, etc.) or any autoimmune, connective tissue, or inflammatory disease that may involve the lungs (e.g., rheumatoid arthritis, Sjögren's syndrome, sarcoidosis, etc.), or previous pneumonectomy. 8.Have a serious infection within 4 weeks prior to the first dose, including but not limited to complications requiring hospitalization, sepsis, or severe pneumonia; or have an active infection requiring systemic anti-infective therapy within 2 weeks prior to the first dose. 9.Have received non-specific immunomodulatory therapy (including but not limited to interferon, IL-2) within 2 weeks prior to dosing. 10.Cannot discontinue the following drugs within 1 week prior to study drug administration and during the study period: strong inducers or strong inhibitors of CYP3A4, or drugs that may prolong the QT interval or cause torsade de pointes. 11.Known previous or current HIV infection; known active syphilis infection; patients who are HCV antibody positive may be enrolled if HCV-RNA is undetectable (lower limit of normal based on the study site's assay) and there is no concurrent hepatitis B virus (HBV) infection. HBV-infected patients may be enrolled if the following criteria are met: For active hepatitis B: at least 6 weeks of antiviral therapy before starting study treatment, HBV DNA <100 IU/mL, and ALT and AST levels <ULN; For resolved or chronic hepatitis B: at least 2 weeks of prophylactic antiviral therapy before starting study treatment, transaminases <ULN, and HBV DNA <100 IU/mL. 12.Are pregnant or breastfeeding; women of childbearing potential and fertile men must agree to use highly effective contraceptive methods during zorifertinib administration and for 3 months after the last dose, and during sacituzumab tirumotecan administration and for 6 months after the last
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Progression-Free Survival; | — |
Secondary
| Measure | Time frame |
|---|---|
| Objective Response Rate;Intracranial Objective Response Rate;Intracranial Progression-Free Survival;Overall Survival; | — |
Countries
China
Contacts
Public ContactRen Shengxiang; Chen Xiaoxia
Shanghai Pulmonary Hospital
Outcome results
None listed