Intracranial activity of amivantamab combined with carboplatin and pemetrexed in epidermal growth factor receptor exon 20 insertion-positive non-small cell lung cancer with brain metastases: a report of three cases.

Background: Epidermal growth factor receptor (EGFR) exon 20 insertion (Ex20ins) mutations in non-small cell lung cancer (NSCLC) are largely insensitive to conventional EGFR tyrosine kinase inhibitors (TKIs) because of steric hindrance in the TKI-binding pocket. Amivantamab, an EGFR-MET bispecific antibody, has been approved for use in combination with chemotherapy as the first-line treatment for EGFR Ex20ins NSCLC. However, intracranial activity remains unknown because monoclonal antibodies are generally thought to have limited central nervous system (CNS) penetration. Case Description: We report three patients with advanced NSCLC with EGFR Ex20ins and with asymptomatic brain metastases who were treated with carboplatin, pemetrexed, and amivantamab (PAPILLON regimen). Case 1 was a 48-year-old woman with ≥10 asymptomatic brain metastases that developed during prior treatment with carboplatin, pemetrexed, and an investigational TKI targeting their Conclusions: These three cases provide clinical evidence that carboplatin, pemetrexed, and amivantamab may exert clinically meaningful intracranial antitumor activity in patients with EGFR Ex20ins NSCLC harboring small, asymptomatic brain metastases. Amivantamab, a bispecific antibody, combined with carboplatin and pemetrexed may exert clinically meaningful intracranial antitumor activity.