A case study published in Oncotarget reports a rare non-small cell lung cancer patient with brain metastases harboring uncommon EGFR mutations responding durably to amivantamab monotherapy after osimertinib failure. Imaging showed complete resolution of CNS lesions at six months maintained at 19 months. This bispecific EGFR-MET antibody demonstrates CNS penetrance and efficacy against rare mutations, challenging existing treatment paradigms and expanding options for patients with limited targeted therapies.