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Activity of patritumab deruxtecan in patients with EGFR inhibitor-resistant NSCLC with EGFR mutations

*August 2021*

Dr. Joel Neal discusses this topic with Dr. Neill Love. Listen to the entire podcast here.

DR LOVE: So another agent we saw some Phase I data on was, patritumab deruxtecan, an anti-HER3 agent. What is it, and what did we learn about it at ASCO?

DR NEAL: Yeah. So this is an antibody-drug conjugate, the deruxtecan the drug conjugate, and patritumab, which is an anti-HER3 antibody. And Pasi Jänne presented these data on the response rate of this in patients that have EGFR-mutant lung cancer and resistance to prior EGFR-TKI, seeing, regardless of a bunch of biomarkers, a response rate almost 40%, PFS of 8 months, and really efficacy suggesting that this HER3 targeting pathway is active.

Now HER3 is not primarily altered in non-small cell lung cancer, but it’s one of the intermediary signals that either MET can signal through or the ERBB family members can signal through HER3, or ERBB3, same thing. And because of that intermediary signaling role, in a way I think of it as being downstream of some of the mechanisms of acquired resistance in EGFR-mutant lung cancer. So it’s not only targeting HER3, but it’s also downregulating and killing those cells with a cytotoxic conjugate.

DR LOVE: And where do you see things heading with this agent?

DR NEAL: Well, just like amivantamab, it looks like it’s active in acquired resistance in EGFR-mutant lung cancer across a spectrum of different acquired resistance mutations. So those response rates of 40% look on the order of what we expect for chemotherapy alone. And since the mechanism of action is different from a small molecule EGFR-TKI or chemotherapy I’d expect it to work independently. So I think this progression-free survival and response rate’s promising. I wonder if some day we might think about combining this with EGFR-TKIs and moving it more to the front-line setting. I’d think about the same thing potentially with amivantamab.