Preliminary results from a phase I–II trial (NCT04072952) evaluating ARV 471, an oral PROTAC that degrades ER in ER-positive breast cancer cells, alone or in combination with palbociclib, in 21 patients affected by metastatic ER+/HER2- breast cancer, showed a 6-months CBR of 42% with a relatively favourable safety profile (no treatment-related grade 3 of 4 adverse events were reported) [100]. The gene discussed is ERBB2; the disease is breast cancer.