VIDEO: Future use of antibody-drug conjugates in EGFR-mutated lung cancer

Editor’s note: This is an automatically generated transcript. Please notify editor@healio.com if there are concerns regarding accuracy of the transcription.

Now as far as what I may be looking forward to in the near future in in the EGFR space, I think on the forefront of everyone's minds or the use of antibody-drug conjugates, and really there's of course plenty of data and certainly a wide array of clinical trials looking at the use of antibody-drug conjugates across the wide spectrum of all lung cancers. But I think there's a special place for antibody-drug conjugates in the context of oncogene-driven tumors, in particular, EGFR mutant lung cancers.

So patritumab deruxtecan (HER3-DXd; Daiichi Sankyo, Merck), which is a HER3-targeting antibody-drug conjugate, there's a lot of promising data with that particular agent. HER3 is actually widely expressed in patients with EGFR disease, and very well might be a resistance mechanism to resistance mechanisms for patients who are treated with a targeted therapy upfront. And it seems that even just a little bit of expression of HER3, you don't necessarily need to have a high-level expression, maybe enough for this particular agent to kind of target in on its particular target.

In addition to patritumab deruxtecan, another promising agent that's already FDA approved in the context of HER2 mutant disease is trastuzumab deruxtecan (Enhertu; AstraZeneca, Daiichi Sankyo). But as we know, trastuzumab deruxtecan also has a pan tumor approval, and there was data that was presented at this most recent World Lung Conference in San Diego that found that among those patients with EGFR disease that also were high expresses of HER2, that there was a fair amount of activity, good clinical activity with trastuzumab deruxtecan for these patients with EGFR mutant tumors that also had high expression of HER2.

And the last thing I'll say is there's a lot of interest certainly with combining antibody-drug conjugates with checkpoint inhibitors, and there's a number of trials ongoing looking at this in wild type tumors, not so much necessarily in EGFR-immune tumors. But like I said, I think there is a special place for antibody-drug conjugates in the context of oncogene-driven tumors. And I think there's strong rationale to potentially combine antibody-drug conjugates with checkpoint inhibitors in the EGFR space, especially in the context of knowing the antibody-drug conjugates in addition to their kind of cytotoxic anti-tumor properties also have a number of distinct immunomodulatory characteristics that might make it a good synergistic partner with checkpoint inhibitors.