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WCLC 2026 | MIST3: bemcentinib and pembrolizumab in relapsed mesothelioma
Dean Fennell, FRCP, PhD, FRSB, University of Leicester & University Hospitals of Leicester NHS Trust, Leicester, UK, discusses the MIST3 trial (NCT03654833), which combines pembrolizumab with bemcentinib, an AXL inhibitor, to treat patients with relapsed mesothelioma, and presents findings on the role of neutrophils and the gut microbiome in predicting sensitivity to this immunotherapy. Targeting AXL can help overcome resistance to immunotherapy and the presence of neutrophils, regulated by the gut microbiome, is closely associated with response to the combination therapy. This interview took place at the IASLC 2026 World Conference on Lung Cancer congress in Seoul, Republic of Korea.
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Transcript
So the MIST3 trial is the third of five trials that we developed for mesothelioma, patients with relapsed disease. It’s an immunotherapy-based study, and we’re combining a PD-1 checkpoint, pembrolizumab, with bemcentinib, which is an AXL inhibitor. And the aim here, and what we’ll be focusing on in this presentation, are the multi-omic studies to try and identify biological features that predict sensitivity...
So the MIST3 trial is the third of five trials that we developed for mesothelioma, patients with relapsed disease. It’s an immunotherapy-based study, and we’re combining a PD-1 checkpoint, pembrolizumab, with bemcentinib, which is an AXL inhibitor. And the aim here, and what we’ll be focusing on in this presentation, are the multi-omic studies to try and identify biological features that predict sensitivity. So AXL is known to be an immune escape mediator, so it actually causes resistance to immunotherapy. By targeting AXL, we’re able to identify that neutrophils, these innate immune cells, were required for responsiveness of the therapy. But moreover, neutrophils appeared to be regulated by the gut microbiome. So we were able to see that the bacterial ecology, the type of bacteria that you have in your gut, seemed to influence whether the neutrophils were present or absent from the tumor. And that in turn seems to be closely associated with response to the combination immunotherapy.
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