Phase 2 elacestrant oral SERD (estrogen receptor degrader) + everolimus mTOR inhibitor in ER+ endometrial cancer

This Phase 2, single-arm interventional study (ELAVERA) at UCLA/Jonsson Comprehensive Cancer Center evaluates elacestrant (an oral selective estrogen receptor degrader that binds ER and promotes receptor degradation) combined with everolimus (an mTORC1 inhibitor that suppresses PI3K/AKT/mTOR signaling and can help reverse endocrine resistance) in recurrent, persistent, advanced, or metastatic ER+ endometrial cancer. Participants take both drugs by mouth once daily continuously on days 1–28 of each 28-day cycle, with imaging (CT ± PET or MRI) and blood collection to track response and safety. The primary endpoint is the 24-week progression-free survival rate, with secondary endpoints including ORR, clinical benefit rate, PFS, and safety. Eligibility includes ER positivity (≥1% by IHC) across histologies; patients must have had prior platinum chemotherapy, and those with dMMR tumors generally must also have received prior immunotherapy. The commercial/scientific angle is endocrine-therapy intensification in a setting where many patients after platinum ± immunotherapy move to options like lenvatinib + pembrolizumab (for pMMR), additional immunotherapy approaches (for dMMR/MSI-H), or cytotoxic chemotherapy, with limited endocrine-based standards despite frequent ER expression in endometrioid tumors.