Abstract 4113: Response to amivantamab, a bispecific EGF and MET receptor directed antibody, in a patient with an atypical EGFR mutated (G719X) non-small cell lung cancer (NSCLC) with leptomeningeal disease who progressed on osimertinib
Authors: Kim Jinah , Choi Horyun , Lee Yeun Ho , Kim Leeseul , Chae Young Kwang 
Published: June 2022

Abstract
Amivantamab is a bispecific antibody against EGF and MET receptors, approved for patients with locally advanced or metastatic NSCLC harboring EGFR exon 20 insertion after disease has progressed on or after platinum-based chemotherapy. Existing data is insufficient in establishing its efficacy on other rare EGFR mutated subtypes, central nervous system (CNS), or its resistance to 3rd generation tyrosine kinase inhibitor (TKI), osimertinib. Here, we report a case showing a good response on single agent amivantamab in an atypical EGFR mutation (G719A, exon18 substitution) NSCLC that progressed to CNS involvement on osimertinib. A 67-year-old male presented with stage IVB squamous cell carcinoma of lung with osseous metastases. CT chest, abdomen, and pelvis revealed a speculated 7.7 cm right upper lung lesion with hilar and subcarinal lymphadenopathies. MRI brain and spine showed multiple bone metastases without CNS involvement. Tissue biopsy confirmed poorly differentiated squamous cell carcinoma with PD-L1 IHC 75%. Tissue next generation sequencing (NGS) showed EGFR G719A. He was started on osimertinib. Two months later, he was hospitalized for drug-induced pneumonitis which prompted off osimertnib. CT angiogram chest showed new diffuse pericardial thickening and nodularity, suggestive of progressive disease. Two cycles of chemotherapy were delivered followed by immunotherapy with ipilimumab and nivolumab. In 10 weeks, progression of disease was revealed in MRI brain demonstrating new parenchymal and leptomeningeal metastases. Amivantamab monotherapy was initiated with discontinuation of immunotherapy. The patient tolerated amivantamab without major complications. His performance status remained the same before and after amivantamab. He denied fatigue, anorexia, nausea or vomiting, however, endorsed rash, which was managed with hydrocortisone cream. Repeat scans in 6 weeks showed decreased leptomeningeal enhancement, and reduction in the size of parenchymal lesions, lung mass, and lymphadenopathies. The highest variant allele fraction from circulating tumor DNA NGS assay from Guardant360 was significantly improved on amivantamab from 25.6% (EGFR G719A), at time of diagnosis, to non-detectable. Amivantamab monotherapy has shown an encouraging outcome in a patient with an atypical EGFR mutated (G719X) NSCLC with leptomeningeal disease who progressed on osimertinib. Our case has shown significant response on CNS involvements, which is contrary to known poor blood-brain barrier penetration of amivantamab. This supports current trial evaluating the efficacy of amivantamab for NSCLC with rare EGFR mutations such as G719X, and ones progressed on 3rd Gen TKI treatment. Additional studies evaluating the efficacy of amivantamab on CNS metastasis are warranted.
Citation Format: Jinah Kim, Horyun Choi, Yeun Ho Lee, Leeseul Kim, Young Kwang Chae. Response to amivantamab, a bispecific EGF and MET receptor directed antibody, in a patient with an atypical EGFR mutated (G719X) non-small cell lung cancer (NSCLC) with leptomeningeal disease who progressed on osimertinib [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 4113.