Another try with patri-dxd
Merck & Co and Daiichi Sankyo are not giving up on their anti-HER3 ADC patritumab deruxtecan just yet. A new clinicaltrials.gov listing has revealed the planned start next month of a fresh phase 3 study, this time in breast cancer. Patri-dxd is an extremely high-profile project, given that Merck handed across $1.5bn for rights to it under a 2023 tie-up. This made withdrawal of a US filing for second-line EGFR-mutant lung cancer an especially hard blow, made worse by full disclosure at ASCO of the disappointing data that caused it, from the Herthena-Lung02 trial. Given toxicities seen in Herthena-Lung02, safety will be something to watch in the new pivotal study, Herthena-Breast04, which aims to enrol 1,000 patients with pretreated, ER-positive, HER2-negative breast cancer, and compare patri-dxd against physician's choice of chemo or Enhertu (presumably owing to this anti-HER2 ADC's availability for HER2-ultralow disease). Daiichi first mooted plans for a phase 3 breast cancer trial back in 2018, wanting to test patri-dxd in HER3-positive disease, but found HER3 expression to be too variable, and testing for it to be insufficiently sensitive. The only nod to this in now is that patients' HER3 status must be known on entry into Herthena-Breast04.
Pivotal trials of patritumab deruxtecan
| Setting | Study | Status |
|---|---|---|
| 2nd-line EGFRm NSCLC | Herthena-Lung02 | No OS benefit & toxicity concerns; US filing withdrawn in May 2025 |
| 2nd-line ER+ve HER2-ve breast cancer | Herthena-Breast04 | Starts 4 Aug 2025 |
| 2nd-line EGFR w/t NSCLC | NA | Plan first announced in 2018, but not pursued |
| 1st-line HER3+ve HER2-ve breast cancer | NA | Plan first announced in 2018, but not pursued owing to conflicting data on detecting HER3 status |
Source: OncologyPipeline.
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