Cetuximab plus Avelumab for Non-small Cell Lung Cancer

Cetuximab

As a recombinant chimeric human/mouse IgG1 monoclonal antibody. Cetuximab is an epidermal growth factor receptor (EGFR) inhibitor drug used to treat metastatic colorectal cancer and head and neck cancer.

In July 2009, Cetuximab (Erbitux) was approved for wild-type KRAS for colon cancer.

Fig.1 The structure of Cetuximab. (Wikipedia)

• Function of Cetuximab
• Enhanced NK cell-mediated ADCC
• Activate the link between natural killer cells (NK) and dendritic cells
• Promote phagocytosis of cancer cells by dendritic cells
• Increases the expression of major histocompatibility complex (MHC) class II molecules and tumor microenvironment T cell aggregation

Avelumab

• Avelumab is a fully human monoclonal antibody drug used to treat Merkel cell carcinoma, renal cell carcinoma, and urothelial carcinoma. Avelumab targets protein programmed death ligand 1 (PD-L1).
• It was approved for the treatment of gastric cancer in January 2017.
• It was approved for the treatment of Merkel cell carcinoma in March 2017.
• It was approved for the treatment of aggressive skin cancer in September 2017.

For more Avelumab products, please search on our website!

Non-Small Cell Lung Cancer

Lung cancer is one of the most common oncological diseases worldwide, and NSCLC is one of its classifications. Approximately 85% of lung cancer patients worldwide are diagnosed with NSCLC. Over the past few decades, treatment of NSCLC has evolved from empiric cytotoxic agents to regimens that are better tolerated and effective by targeting specific molecular subtypes. At present, the important intervention targets of NSCLC treatment mainly include EGFR, ALK, HER2, ROS1, BRAF, MET, and NTRK.

Fig.2 Subtype characterization of non-small cell lung cancer.¹

Method

This article evaluated ADCC activity in NSCLC using a lactate dehydrogenase (LDH) release assay. In addition, the antitumor activity and safety of Avelumab plus Cetuximab were evaluated using a single-arm proof-of-concept study. This study also measured predictive biomarkers.

Results

Fig.3 Assessment of natural killer (NK) activation and cytotoxic lytic activity after treatment with Cetuximab and/or Avelumab.²

Fig.4 Assessment of overall survival (OS) and progression-free survival (PFS).²

Fig.5 Assessment of natural killer (NK) activation and cytotoxic lytic activity after Cetuximab plus Avelumab treatment.²

Conclusion

• Treatment with Cetuximab plus Avelumab activates NK cells in NSCLC patients.
• In-vitro evaluation of circulating DNA levels, ADCC, and early cutaneous toxicity can predict the efficacy of Cetuximab plus Avelumab in NSCLC.

References

1. Relli, V.; et al. Abandoning the notion of non-small cell lung cancer. Trends in molecular medicine. 2019, 25(7): 585-594.
2. Fasano, M.; et al. Induction of natural killer antibody-dependent cell cytotoxicity and of clinical activity of Cetuximab plus Avelumab in non-small cell lung cancer. ESMO open. 2020, 5(5): e000753.