The Phase I/II AMEERA-1 clinical trial (NCT03284957) evaluates the safety and efficacy of amcenestrant, an oral selective estrogen receptor (ER) degrader (SERD) with palbociclib, everolimus, alpelisib and abemaciclib in women with ER-positive/HER2-negative advanced breast cancer. In this video, Mario Campone, MD, PhD, Cancérologie de l’Ouest, René Gauducheau, St Herblain, France, shares an update on the results from the analysis of the subgroup receiving palbociclib plus amcenestrant in dose escalation and dose expansion. This combination had an acceptable safety profile in comparison to other oral SERDs, with neutropenia and stomatitis as the most common side effects. The trial reported a response rate (RR) of 32% and a clinical benefit of 73% for patient in both the dose escalation and dose expansion groups, and irrespective of ESR1 mutation status and of other genomic alterations. This combination is going to be tested in a Phase III trial in comparison to palbociclib plus letrozole. This interview took place at the European Society for Medical Oncology (ESMO) 2021 congress.