Data from Exploration of Immune-Modulatory Effects of Amivantamab in Combination with Pembrolizumab in Lung and Head and Neck Squamous Cell Carcinoma

AbstractImmune checkpoint inhibitors are effective first-line therapy for solid cancers. However, low response rate and acquired resistance over time has led to the need for additional therapeutic options. Here, we evaluated synergistic antitumor efficacy of EGFR × MET targeting bispecific antibody, amivantamab with PD-L1 immunotherapy, pembrolizumab in head and neck squamous cell carcinoma (HNSCC) and lung squamous cell carcinoma tumor–bearing humanized patient-derived xenograft (PDX) models. We demonstrated that pembrolizumab or amivantamab alone was ineffective and that combination treatment induced a significant reduction of tumor growth in both models (P P P HIGHMETHIGH subcluster displayed an increased expression of genes implicated in production of lactate SLC16A3 and lactate dehydrogenase A (LDHA) compared to the EGFRLOWMETLOW cluster. Accumulation of lactate in the TME has been associated with immunosuppression by hindering the infiltration of tumor killing CD8 T and NK cells. This study proved that amivantamab reduced glycolytic markers in the EGFRHIGHMETHIGH subcluster including SLC16A3 and LDHA and highlighted remodeling of the TME by combination treatment, providing rationale for additional therapy of amivantamab with PD-1 immunotherapy.Significance:Amivantamab in synergy with pembrolizumab effectively eradicated EGFRHIGHMETHIGH tumor subcluster in the tumor microenvironment of head and neck squamous cell carcinoma and overcame resistance against anti-PD-1 immunotherapy.