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(Abstract)

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A study presented at the WCLC 2023 conference explored the efficacy of combining the drugs Mobocertinib and Amivantamab in treating EGFR ex20ins non-small cell lung cancer. Both drugs have received accelerated approval for single-agent use in this patient population. The researchers hypothesized that the combination therapy could further benefit these patients. <br /><br />The study tested the combined efficacy of Mobocertinib and Amivantamab in two human patient-derived xenograft (PDX) models of EGFR ex20ins NSCLC. The results showed that Mobocertinib alone had dose-dependent efficacy in inhibiting tumor growth, while Amivantamab alone had limited efficacy. However, when Amivantamab was combined with a suboptimal dose of Mobocertinib, there was enhanced benefit observed compared to Mobocertinib alone. <br /><br />Further molecular characterization with RNA and whole exome sequencing revealed specific genes and pathways associated with drug response and signaling in the tumors. The combination therapy activated pathways associated with cell-cycle checkpoints, MYC targets, and mTORC1, while downregulating apoptosis, IL2/STAT5, and inflammatory response pathways. <br /><br />Overall, the combination of Mobocertinib and Amivantamab showed synergetic efficacy in the PDX models. The study identified unique resistant molecular profiles to single-agent or combination treatments. Further testing of this combination therapy is warranted to potentially improve outcomes for patients with EGFR ex20ins NSCLC.

Asset Subtitle

Sampurna Chatterjee

Meta Tag

Speaker Sampurna Chatterjee

Topic Metastatic NSCLC: Targeted Therapy - EGFR/HER2

Keywords

WCLC 2023 conference

drug combination therapy

Mobocertinib

Amivantamab

EGFR ex20ins non-small cell lung cancer

accelerated approval

patient-derived xenograft (PDX) models

tumor growth inhibition

molecular characterization

synergetic efficacy