∙ Participants must meet all of the following inclusion criteria to be eligible for this study:

• Signed written informed consent and ability to comply with the scheduled visits and study procedures outlined in the protocol.

• Age ≥ 18 years, any gender.

• Histologically or cytologically confirmed locally advanced or metastatic non-small cell lung cancer (mainly adenocarcinoma) not suitable for curative surgery or radiation therapy.

• ECOG Performance Status (ECOG PS) score of 0-1. Expected survival of at least 12 weeks.

• Prior treatment with a third-generation EGFR tyrosine kinase inhibitor (TKI) targeted therapy, with radiological evidence of disease progression. The last treatment before enrollment must show radiological evidence of disease progression, intolerance to chemotherapy toxicity, or the patient being ineligible for standard treatment or unable to tolerate the current treatment regimen.

• At least one measurable lesion according to the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria that has not been previously irradiated.

• Tissue, plasma, or cytological samples collected after disease progression confirmed by imaging following treatment with a third-generation EGFR TKI, demonstrating an EGFR-positive gene mutation sensitive to EGFR TKI treatment (including exon 19 deletion, 21 L858R mutation, etc.), with or without T790M mutation.

• Adequate organ and bone marrow function, with clinical laboratory test results meeting the following criteria:

‣ Hematology: Neutrophils ≥ 1.5 × 10\^9/L; Platelets ≥ 100 × 10\^9/L; Hemoglobin (Hgb) ≥ 100 g/L;

⁃ Liver function: Total bilirubin (TBIL) ≤ 1.5 × upper limit of normal (ULN) (≤3 × ULN for patients with Gilbert's syndrome); Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 × ULN;

⁃ Renal function: Serum creatinine (Cr) ≤ 1.5 × ULN or creatinine clearance rate (CCr, Cockcroft-Gault formula) ≥ 50 mL/min; Semi-quantitative urine testing (e.g., urine dipstick) result showing urine protein \< 2+; patients with urine protein ≥ 2+ at baseline should undergo a 24-hour urine collection, and the protein content in the urine within 24 hours should be \< 1g;

⁃ Coagulation function: Activated partial thromboplastin time (APTT) and international normalized ratio (INR) both ≤ 1.5 × ULN;

⁃ Cardiac function: Left ventricular ejection fraction (LVEF) ≥ 50%;

⁃ At rest, male QTcF \< 450 msec or female QTcF \< 470 msec.

• Ability to swallow oral medications.

⁃ Reproductive-age female patients must agree to use effective contraception throughout the study period until 60 days after discontinuing BPI-1178 and osimertinib. Female patients must have a negative pregnancy test result before the start of treatment or prove the absence of pregnancy possibility. Male patients must agree to use effective contraception throughout the study period until 120 days after discontinuing BPI-1178 and osimertinib.

⁃ Apart from stable Grade 2 peripheral neuropathy (CTCAE v5.0) and alopecia, any treatment-related clinical toxicity before enrollment must have recovered to baseline or Grade 1.

⁃ All patients must have sufficient mental capacity to understand the nature, significance of the study, and risks associated with the study.