2023 World Conference on Lung Cancer (Posters)-P2.09. Enhanced in Vivo Efficacy of Mobocertinib and Amivantamab Combination in EGFR ex20ins+ NSCLC PDX Models

P2.09. Enhanced in Vivo Efficacy of Mobocertinib and Amivantamab Combination in EGFR ex20ins+ NSCLC PDX Models - PDF(Slides)

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In this study, the researchers investigated the potential synergistic effects of combining mobocertinib and amivantamab in treating patients with EGFR exon 20 insertion–positive non-small cell lung cancer (NSCLC). Both drugs have been individually approved for the treatment of this specific type of lung cancer. The study evaluated the efficacy of the combination therapy in several patient-derived xenograft (PDX) models and an engineered cell line.<br /><br />The results showed that the combination of mobocertinib and amivantamab had synergistic effects in inhibiting tumor growth in the PDX models. Specifically, the combination therapy resulted in greater growth inhibition compared to either drug alone in the EGFR S768dupSVD and EGFR H773insNPH models. In the EGFR A767dupASV model, the combination of mobocertinib and amivantamab was more effective than mobocertinib alone in suppressing tumor growth. In the EGFR V769insASV cell line model, the combination therapy exhibited greater tumor inhibition compared to individual therapies.<br /><br />Furthermore, molecular characterization of the tumor samples revealed changes in signaling pathways and gene expression associated with the combination therapy. The combination of mobocertinib and amivantamab resulted in the activation of pathways related to cell-cycle checkpoints and MYC targets, suggesting potential mechanisms for the enhanced efficacy of the combination therapy.<br /><br />Overall, the study findings suggest that the combination of mobocertinib and amivantamab has synergistic efficacy in EGFR exon 20 insertion–positive NSCLC. This combination therapy may provide a potential treatment option for patients with this hard-to-treat patient population. Further clinical studies are warranted to confirm these findings and evaluate the safety and efficacy of the combination therapy in patients.

Asset Subtitle

Sampurna Chatterjee

Meta Tag

Speaker Sampurna Chatterjee

Topic Metastatic NSCLC: Targeted Therapy - EGFR/HER2

Keywords

mobocertinib

amivantamab

EGFR exon 20 insertion–positive non-small cell lung cancer

combination therapy

tumor growth inhibition

synergistic effects

patient-derived xenograft models

engineered cell line

signaling pathways

gene expression