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The Rationale for Bemcentinib Plus Pembrolizumab in AXL-Positive NSCLC

Matthew Krebs, MBChB, PhD
Published Online:5:00 PM, Tue February 11, 2020


Matthew Krebs, MBChB, PhD, a clinical senior lecturer in Experimental Cancer Medicine at the University of Manchester, explains the rationale for a phase II study of bemcentinib (BGB324), a first-in-class selective AXL inhibitor, in combination with pembrolizumab (Keytruda) in patients with advanced non–small cell lung cancer, which he presented at the 2019 Society for Immunotherapy of Cancer (SITC) Annual Meeting.

AXL drives epithelial-mesenchymal transition and resistance to cytotoxic T-cell mediated cell death. If AXL inhibition is administered in the preclinical setting, the AXL positivity can be reduced, making the cells more susceptible to T-cell-mediated killing. This ability is what makes AXL inhibitors ideal for combination with immune checkpoint inhibitors, says Krebs.

Additionally, in vivo models that evaluated bemcentinib in combination with immune checkpoint inhibitors demonstrated synergy between these two types of therapy in lung cancer and in other malignancies.

For more about the phase II study from SITC 2019: https://www.targetedonc.com/news/adjuvant-immunotherapy-combination-shows-activity-in-axlpositive-nsclc
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