Patritumab deruxtecan (HER3-DXd) in EGFR inhibitor-resistant, EGFR-mutated NSCLC

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Published: 11 Jun 2021
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Dr Christina Baik - University of Washington School of Medicine, Seattle, USA

Dr Christina Baik talks to ecancer about her study looking at the efficacy and safety of patritumab deruxtecan as treatment in EGFR inhibitor-resistant EGFRm NSCLC.

Dr Baik beings by explaining that the study was a single arm study in patients with EGFRm NSCLC. The study began as a dose escalation study and then expanded into a larger cohort, stating that once the safe dosage was found during the dose escalation study then expanded to a larger study where everybody was being evaluated at the chosen dose.

She then goes on to explain the findings, saying that in the very heavily treated patient population a meaningful efficacy rate was observed, with the response rate being close to 40% and the progression-free survival being around 8 months.

Dr Baik concludes by explaining that there is an ongoing study that is meant to be a confirmatory and registrational study (in the US), looking at 2 different doses to determine the best dose going forward. Once that confirmatory trial shows similar efficacy rates then they're hoping to see patritumab deruxtecan become approved y regulatory bodies.

ecancer's filming has been kindly supported by Amgen through the ecancer Global Foundation. ecancer is editorially independent and there is no influence over content.

This was a study investigating a drug called U3-1402, also called partritumab deruxtecan. What it is, is an antibody-drug conjugate to a protein called HER3, so it’s an anti-HER3 antibody-drug conjugate. This study was a single arm study in patients with EGFR mutated non-small cell lung cancer. The study started out as a dose escalation study and then expanded into a larger cohort and the data is coming from that single arm study.

What was the methodology used in this study?

As I mentioned briefly, this was a dose escalation study initially, meaning that there were several doses that were investigated and once a safe dose was found then it expanded to a larger study where everybody was being evaluated at the chosen dose. It was a single arm study, there was no comparator, but there were a good number of patients for us to get very good and confident efficacy data.

What were your findings?

The finding was that in this very heavily treated patient population we saw a very meaningful efficacy rate, meaning the response rate was close to 40%, the progression free survival was around 8 months. Very high rates of disease control, meaning that either patients had a response or stable disease, in the 70% range which is very meaningful because the patients that were in this trial, the average prior lines of therapy was four, which is quite a bit. Typically after somebody has gone through four lines of therapy we wouldn’t really expect very much efficacy for chemotherapies and other agents after that. So the fact that we’re seeing durable responses, that was very exciting to us and that is, in my opinion, clinically very meaningful.

How can these results impact the future treatment of NSCLC?

This drug is not yet available for patients outside of a trial. Having said that, we hope and anticipate this drug to be available. The way it’s going to be used is likely in this setting where patients have progressed on their initial targeted therapies. Just to remind you, these are patients with a specific mutation, namely an EGFR mutation, who have a number of targeted therapy options. So these are patients who progress on these targeted therapies and likely have received a standard platinum-based chemotherapy and after that this would be an option for those patients.

One thing that I should point out is that this particular drug showed efficacy across multiple resistance alterations in these patients, meaning that patients responded regardless of whatever genomic change their tumour had evolved after their initial TKI therapy. So far it doesn’t look to be restricted to a certain HER3 protein expression so this drug could become a treatment across all EGFR patients who have had at least the targeted therapies.

What is next for this study?

Next there is an upcoming or ongoing study that is meant to be a confirmatory and registrational study, at least in the US. It’s looking at two different doses to really determine the best dose to move forward. It’s enrolling many patients beyond the ones that were enrolled in this phase I study. Once that confirmatory trial shows similar efficacy rates then we are hoping to see this drug become approved by regulatory bodies.

Is there anything else important that you would like to mention?

The last thing I would say is that for EGFR mutated patients it’s very exciting to see newer treatments being developed in this patient population. There are lots of developments so this field will continue to evolve and we’ll just to have to pay attention to what’s happening.