The Lung Cancer Channel is supported with funding from Johnson & Johnson (Gold) and Takeda (Gold).
VJOncology is an independent medical education platform. Supporters, including channel supporters, have no influence over the production of content. The levels of sponsorship listed are reflective of the amount of funding given to support the channel.
ESMO Asia 2025 | Novel strategies targeting c-Met in non-small cell lung cancer
Hidehito Horinouchi, MD, PhD, National Cancer Center Hospital, Tokyo, Japan, discusses the importance of understanding MET alterations in non-small cell lung cancer, including mutations, amplifications, overexpression, and fusions. There is additionally a re-emerging focus on MET overexpression due to the development of antibody drug conjugates (ADCs) such as ABBV-400 (telisotuzumab adizutecan) and ABBV-399 (telisotuzumab vedotin). MET overexpression is the most frequent type of alteration in the MET field and that ADCs targeting MET overexpression have shown promising efficacy and safety profiles, with differences in payload leading to distinct outcomes. This interview took place at 2025 European Society for Medical Oncology (ESMO) Asia Congress in Singapore, Singapore.
These works are owned by Magdalen Medical Publishing (MMP) and are protected by copyright laws and treaties around the world. All rights are reserved.
Transcript
Yes, so I’d like to cover the MET alterations as a whole. So now, because MET alterations have been focused on the MET exon-14 skipping mutation covered by the MET TKI like capmatinib, tepotinib, and several other ones. So, however, now we have several other targeted agents in this field. So, but before getting into this MET talk, I’d like to share the very important information about MET acronyms...
Yes, so I’d like to cover the MET alterations as a whole. So now, because MET alterations have been focused on the MET exon-14 skipping mutation covered by the MET TKI like capmatinib, tepotinib, and several other ones. So, however, now we have several other targeted agents in this field. So, but before getting into this MET talk, I’d like to share the very important information about MET acronyms. So, recently in the JTO publication, we have a great editorial covering the misleading interpretation of the MET gene acronyms. So in this editorial, Leliga L.O. has been provided very important insights that MET is not coming from the mesenchymal, epidermal, epithelial transition as a gene name. So this is very important. Even the chat GPT has been provided a mistakenly misleading answer. So that please be careful. But in the right, in the appropriate manner, the MET gene acronyms are coming from the original presentation or publication of Nature 1984. This MET is coming from the cancer-inducing chemical MNG. So this METO something is the original name. It’s related to the MET. So the first portion of this chemical agent is turning into the acronyms of the MET. So first of all, I’d like to provide an important information. Do not misread the MET as a gene name. So when we check the MET alterations, we have several ways to target the MET alteration. We have the MET mutation, like the exon-14 skipping mutation, and MET amplification, and MET overexpression, and MET fusion. So in the previous years, very older days, we have the MET overexpression clinical trial using the onartuzumab as a MET antibody in combination with erlotinib. However, the trial showed a MET lung trial showed a huge failure. So based on such kind of a failure, we have a little bit long vacant time for the METs targeting antibody agent. So, however, after this several, almost 10 years or something absent period, we have now gotten back into the MET overexpression area again. So when, because the, when we compare the MET mutation, MET amplification, and MET overexpression again. So when we compare the MET mutation, MET amplification, and MET overexpression and MET fusion, MET overexpression is the most frequent type of alteration in the MET field. So why we have the re-emerging focus on the MET overexpression? That is a keyword is antibody drug conjugate. So we have several good antibody drug conjugates targeting the MET overexpression. So including them is several ones that one is one important one, ABBV-400. So the ABBV-400 is provided by AbbVie. And also we have the ABBV-399. Only one number change. However, these two MET targeting agents are a huge educational one because these two ADCs have shared the same antibody, terisotuzumab. However, the payload is different. Velotin for the ABBV-399, and a topoisomerase 1 inhibitor, aducantrabed for the terisotuzumab ABBV-400, terisotuzumab. So based on this, a little bit different situation by the payload, these two agents are having the contrasting and very interesting efficacy and safety profile difference. Especially the efficacy signal is quite different. So that when it comes to the Teliso-B, we need MET overexpression as a key for selecting the best patient to be treated. However, in telisotuzumab adizutecan ABBV-400 example, there is no need to select a MET overexpressed patient population. Although the efficacy signal is stronger in the higher MET overexpression patient population, however, when we use that topoisomerase 1 inhibitor as a payload, TEMAB-A showed a similar efficacy signal like the MET-selected teresomy experiences. So that is a great example of how we can develop the better ADC even using the same antibody. So based on such kind of great examples, we have the several MET-targeting ADCs right now. So that makes us very enthusiastic to check the MET overexpression in addition to the MET amplification mutations. So that is a background information why we are now re-entering the MET area, especially based on the MET overexpression. Thank you.
This transcript is AI-generated. While we strive for accuracy, please verify this copy with the video.
Read more...
