Inclusion Criteria:  Male or female; Age: ≥ 18 years; Expected survival time ≥ 3 months;  Histopathologically and/or cytologically confirmed locally advanced or metastatic NSCLC patients who are enrolled in 3 cohorts:  A) patients progressed on prior 1st line or 2nd line 3rd generation EGFR-TKI treatment; B) patients progressed on prior 1st line 1st or 2nd generation EGFR-TKI treatment and with T790M negative mutation; C) patients with EGFR exon20ins mutation;  Agree to provide archival tumor tissue samples or fresh tissue samples of the primary tumor or metastases within 6 months; if the subject cannot provide tumor tissue samples, they can be evaluated by the investigator if they meet other inclusion and exclusion criteria; Must have at least one measurable lesion as defined by RECISTv1.1; Performance status score ECOG0 or 1; Toxicities from prior anticancer therapy have recovered to grade ≤ 2 as defined by NCI-CTCAEv5.0 (except alopecia); No severe cardiac dysfunction, left ventricular score ≥ 50%;  The level of organ function must meet the following criteria:  Bone marrow function: Absolute neutrophil count (ANC) ≥ 1.5 × 109/L, platelet count ≥ 80 × 109/L, hemoglobin ≥ 90 g/L; Liver function: TBIL ≤ 1.5ULN (total bilirubin ≤ 3ULN for subjects with Gilbert's syndrome, liver cancer or liver metastases); AST and ALT ≤ 2.5ULN for subjects without liver metastases; AST and ALT ≤ 5.0ULN for subjects with liver metastases; Renal function: creatinine (Cr) ≤ 1.5ULN, or creatinine clearance (Ccr) ≥ 50 mL/min (according to CockcroftandGault formula). Coagulation function: international normalized ratio (INR) ≤ 1.5 × ULN, and activated partial thromboplastin time (APTT) ≤ 1.5ULN; Urine protein ≤ 2 + (measured by dipstick) or < 1000 mg/24 h (urine); Premenopausal women of childbearing potential must have a negative serum or urine pregnancy test 7 before starting treatment and must be non-lactating; all patients (male or female) should take adequate barrier contraception measures throughout the treatment cycle and 6 months after the end of treatment.  Exclusion Criteria:  Patients with MET, ALK, RET, HER2 mutations suggested by gene sequencing; Patients who have previously received systemic chemotherapy in the first/second line of systemic therapy; Use chemotherapy, biological therapy, immunotherapy, radical radiotherapy, major surgery before the first dose; History of significant cardiac disease, such as: symptomatic congestive heart failure (CHF) ≥ grade 2 (CTCAE 5.0) history, New York Heart Association (NYHA) ≥ grade 2 heart failure, acute coronary syndrome, etc.; QT prolongation (QTc > 450 msec in men or QTc > 470 msec in women), complete left bundle branch block, third degree atrioventricular block; Active autoimmune diseases and inflammatory diseases, such as systemic lupus erythematosus, psoriasis requiring systemic treatment, rheumatoid arthritis, inflammatory bowel disease and Hashimoto's thyroiditis, except for type I diabetes, hypothyroidism controllable by replacement therapy only, skin diseases not requiring systemic treatment (such as vitiligo, psoriasis); Other malignancies diagnosed within 5 years prior to first dose, Exceptions include: radical basal cell carcinoma of the skin, scaly cell carcinoma of the skin, and/or radical resection of carcinoma in situ; Hypertension poorly controlled by two antihypertensive drugs (systolic blood pressure > 150 mmHg or diastolic blood pressure > 100 mmHg); Pulmonary disease defined as ≥ grade 3 according to CTCAEv5.0, including resting dyspnea, or requiring continuous oxygen therapy, or patients with a history of interstitial lung disease (ILD); Symptoms of active central nervous system metastases.However, patients with stable parenchymal metastases can be stable, and whether it is stable or not is judged by the investigator; Patients with a history of hypersensitivity to recombinant humanized antibodies or human-mouse chimeric antibodies or hypersensitivity to SI-B001 or any of the excipient components of Osimertinib; History of autologous or allogeneic stem cell transplantation; In previous anthracycline (neo) adjuvant therapy, the cumulative dose of anthracycline was > 360 mg/m2; Human immunodeficiency virus antibody (HIVAb) positive, active tuberculosis, active hepatitis B virus infection (HBV-DNA copy number > 104) or hepatitis C virus (HCV) infection; Active infection requiring systemic treatment, such as severe pneumonia, bacteremia, sepsis, etc.; Received other unmarketed clinical study drugs or treatments before participating in the study;