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ASCO 2021 | Patritumab deruxtecan in patients with EGFR-mutant NSCLC

Pasi Jänne, MD, PhD, Dana-Farber/Harvard Cancer Center, Boston, MA, provides an overview of the Phase I trial (NCT03260491) assessing patritumab deruxtecan, a HER3-directed antibody-drug conjugate (ADC), in patients with EGFR-mutant non-small cell lung cancer (NSCLC). The expansion study included patients with EGFR inhibitor-resistance and there was an overall response rate (ORR) of 39% as well as a median progression-free survival (PFS) of 8.2 months. Prof. Jänne additionally discusses a Phase II trial of patritumab deruxtecan in NSCLC (NCT04619004). This interview took place at the American Society of Clinical Oncology (ASCO) 2021 Virtual Meeting.

Transcript (edited for clarity)

This is a trial of a drug called patritumab deruxtecan, also know as HER3-DXd, which is a HER3 antibody-drug conjugate. And the trial was specifically in patients with EGFR-mutant lung cancer who had developed resistance to prior EGFR TKIs.

And the rationale for the trial is that many, if not all, EGFR-mutant cancers also co-express HER3, but HER3 is not a known resistance mechanism to EGFR inhibitors...

This is a trial of a drug called patritumab deruxtecan, also know as HER3-DXd, which is a HER3 antibody-drug conjugate. And the trial was specifically in patients with EGFR-mutant lung cancer who had developed resistance to prior EGFR TKIs.

And the rationale for the trial is that many, if not all, EGFR-mutant cancers also co-express HER3, but HER3 is not a known resistance mechanism to EGFR inhibitors. And so by targeting HER3, you could have a novel approach to treating these cancers that’s agnostic to how they became resistant to prior therapies.

And in this trial, which is a phase one trial followed by an extension cohort, we treated patients who had developed resistance to EGFR TKIs and, in many cases, chemotherapy as well, and saw a confirmed response rate of 39% and a PFS of 8.2 months. And, as predicted from the mechanism, we saw activity in patients with known resistance mechanisms, such as secondary EGFR mutations or those with bypass signal pathway activation, and also in patients that did not have a known resistance mechanism, and suggesting that this may be a mechanism agnostic strategy to treat patients that have developed resistance to EGFR inhibitors.

So this trial, this is the first expansion cohort in this trial. There’s a second expansion cohort, which has completed enrollment also in EGFR-immune patients. There is a phase two trial now ongoing as a single agent for patients that have been treated with prior osimertinib and chemotherapy, EGFR-mutant patients. And there’s also a phase one trial ongoing for EGFR-mutant patients combining osimertinib with HER3-DXd in patients that have been treated with just prior osimertinib.

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Disclosures

Dr Jänne reports consultancy to Daiichi Sankyo and receives sponsored research support from Daiichi Sankyo.

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