AMEERA-1: Phase 1-2 Study of Amcenestrant, An Oral Selective Estrogen Receptor Degrader, With Palbociclib in Postmenopausal Women With ER+ HER2- Metastatic Breast Cancer - Episode 4

Amcenestrant and Its Effects on ER+/HER2- Metastatic Breast Cancer

An expert introduces amcenestrant as a potential new therapy for ER+/HER2- metastatic breast cancer and addresses how it differs from current treatment options.

Sarat Chandarlapaty, MD: Amcenestrant is a form of hormone therapy. It’s what’s called a selective estrogen receptor degrader. That means it’s a drug that binds to the estrogen receptor or an estrogen receptor antagonist. It does so in a way that causes the receptor to be degraded as part of its effects. This class of agents, these selective estrogen receptor degraders, includes an already approved drug, fulvestrant. Amcenestrant was designed to improve on existing estrogen receptor inhibitors, like fulvestrant or even tamoxifen, by overcoming some of those limitations those drugs have.

What are those limitations? Some of the limitations of those drugs are pharmacological. They don’t get to very high consistent levels in patients. That is, they’re not highly bioavailable. Fulvestrant particularly has to be given as an intramuscular injection every month, and it doesn’t achieve high consistent levels over time. That lack of bioavailability ultimately limits the efficacy of those drugs. The other limitations may be in their potency, particularly tamoxifen. What we’ve learned in the last few years is that estrogen receptors are subject to genetic mutations that lead to a constitutively active form, and those constitutively active forms will require even more potent ER [estrogen receptor] antagonists to inhibit. Amcenestrant is designed to be a more potent and more bioavailable estrogen receptor inhibitor.

The AMEERA trials have been the platform for the first-in-human all the way to up to phase 3 studies of amcenestrant in advanced breast cancer. The first-in-human study, the AMEERA-1 study, really evaluated amcenestrant as a single agent and demonstrated in dose escalation, as well as in the recommended dose, that amcenestrant is a very selective and safe molecule. The adverse-effect profile was very consistent with a pure antiestrogen. There were no grade 3 treatment-related adverse events with the drug. The adverse-effect profile was the typical antiestrogen adverse effect, with the No. 1 adverse effect being hot flashes, then low-grade joint aches or arthralgias, and constipation. Importantly, what was not seen was ophthalmologic or cardiac adverse effects.

Transcript edited for clarity.