Phase 2 elacestrant SERD + trastuzumab/pertuzumab HER2 mAbs in triple-positive breast cancer.

This Phase 2 NYU Langone Health investigator-led study (ELATE; NCT07612215) evaluates the safety and anti-tumor activity of adding elacestrant—an oral selective estrogen receptor degrader (SERD) that binds ER and promotes its degradation—to dual HER2 blockade with trastuzumab (HER2-directed monoclonal antibody) plus pertuzumab (HER2 dimerization–blocking monoclonal antibody). The design uses two parallel cohorts based on ESR1 status (wild-type vs mutated), reflecting that ESR1 mutations are a common acquired resistance mechanism in ER+ metastatic disease (often emerging after aromatase inhibitors) and may be enriched after multiple endocrine lines. Although the sponsor is NYU Langone Health, elacestrant is marketed/developed by Menarini Group (Stemline Therapeutics) and Pfizer; trastuzumab and pertuzumab are from Genentech/Roche. The scientific angle is whether a next-generation oral SERD can improve endocrine control while maintaining chemotherapy-sparing HER2 dual-antibody backbone in later-line “triple-positive” disease. Today’s care after progression typically relies on sequential HER2-directed regimens (often ADC-based, such as trastuzumab deruxtecan, or tucatinib-based combinations) with endocrine therapy sometimes layered in, so this explores a targeted, all-biologic + oral endocrine combination to extend benefit without cytotoxic chemo.