Aumolertinib with timed chemotherapy for newly treated EGFR L858R lung adenocarcinoma

Who can take part

• Individuals must be at least 18 years of age at the time of signing the informed consent form
• Participants must demonstrate the ability to understand the study procedures and provide written informed consent before any trial-specific activities begin
• A confirmed diagnosis of lung adenocarcinoma (LUAD) via histological or cytological examination is required. The disease must be in an advanced or metastatic stage (stage IIIB, IIIC, or IV by AJCC TNM staging system 9th edition) that is not suitable for curative-intent surgery or radiation therapy
• Documentation of an EGFR L858R mutation is mandatory. This status can be confirmed using tumor tissue or plasma-based molecular testing
• Participants must not have received prior systemic therapy for advanced or metastatic LUAD. Previous adjuvant or neoadjuvant treatments are allowed if they were completed at least 12 months before the first dose of the study medication
• An Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 is required. The estimated life expectancy of the participant must be at least three months
• Participants must have at least one measurable lesion that has not been previously irradiated, as defined by RECIST 1.1 criteria
• Adequate physiological function must be demonstrated within 14 days before the start of treatment, including:; Bone Marrow: Absolute neutrophil count ≥ 1.5 x 10\^9/L, platelet count ≥ 100 x 10\^9/L, and hemoglobin ≥ 9.0 g/dL; Hepatic: Total bilirubin ≤ 1.5 x upper limit of normal (ULN); aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN, or ≤ 5 x ULN if liver metastases are present; Renal: Serum creatinine ≤ 1.5 x ULN or a calculated creatinine clearance ≥ 45 mL/min
• Reproductive Safety: Participants of childbearing potential must agree to use highly effective contraception throughout the study and for a specified period after the final dose of the investigational products

Who cannot take part

• Patients with symptomatic or unstable central nervous system metastases. However, participants with symptomatic or unstable brain metastases who have completed local treatment and are off high-dose corticosteroids (>10 mg/d prednisone or equivalent) for at least two weeks may be considered eligible
• Concomitant Infections: Active infections requiring systemic therapy. Patients with HBV infection may be eligible if their have received adequate antiviral treatment (antiviral treatment ≥ 7 days before the first dose of the study medication)
• Medication Interference: Ongoing use of potent CYP3A4 inhibitors or inducers, as these may significantly alter the plasma concentrations of aumolertinib
• Severe Comorbidities:; Cardiac: History of clinically significant cardiovascular disease, such as uncontrolled hypertension, congestive heart failure (NYHA Class II or higher), or a recent myocardial infarction within the last six months; Pulmonary: Known history of interstitial lung disease (ILD) or drug-induced ILD that required steroid treatment; Gastrointestinal: Malabsorption syndromes or chronic inflammatory bowel disease that could interfere with the absorption of oral aumolertinib
• Other Malignancies: A history of another active primary malignancy within the last three years, except for adequately treated non-melanoma skin cancer or in situ carcinoma elsewhere
• Hypersensitivity: Known hypersensitivity to aumolertinib, pemetrexed, carboplatin, or any of the excipients used in these formulations
• Any previous treatment with EGFR tyrosine kinase inhibitors, including first-, second-, or third-generation agents (e.g., gefitinib, afatinib, or osimertinib)