AMAZE-lung: Amivantamab, Lazertinib and Bevacizumab in Patients With EGFR-mutant Advanced Non-small Cell Lung Cancer With Progression on Previous Third-generation EGFR-TKI

Histologically confirmed non-squamous NSCLC, stage IIIB/C (not amenable to radical therapy) or stage IV according to 8th TNM classification.Presence of a sensitising EGFR-mutation (only patients with exon 19 deletion and/or L858R are eligible) and documentation of T790M status, tested locally by an accredited laboratory. Radiologically confirmed disease progression on previous treatment with osimertinib or lazertinib.Treatment with osimertinib must have been stopped at least 8 days before enrolment. Achieved objective clinical benefit from osimertinib or lazertinib treatment (e.g., documented PR/ CR or SD for ≥6 months while on osimertinib or lazertinib treatment). Measurable disease as defined according to RECIST v1.1. Age ≥18 years. Eastern Cooperative Oncology Group (ECOG) performance status 0-2. Life expectancy ≥12 weeks.

Adequate haematological function:

Haemoglobin ≥100 g/L,Absolute neutrophil count (ANC) ≥1.5× 109/L, Platelet count ≥75× 109/L.

Adequate renal function:

- Serum creatinine <1.5× ULN and calculated (Cockcroft-Gault formula) or measured creatinine clearance >45 mL/min.

Adequate liver function:

ALT and AST ≤3× ULN. If the patient has liver metastases, ALT and AST must be ≤5× ULN.Total bilirubin ≤1.5× ULN. Patients with Gilbert's syndrome are eligible if conjugated bilirubin is within normal limits. Women of childbearing potential, including women who had their last menstruation in the last 2 years, must have a negative pregnancy test (b-human chorionic gonadotropin [b-hCG]) within 5 weeks before enrolment and within 3 days before the first dose of protocol treatment. Women of childbearing potential must use highly effective contraceptive methods. Written IC for trial participation must be signed and dated by the patient and the investigator prior to any trial-related intervention.