ETX-636 + fulvestrant

ETX-636 + fulvestrant is a pharmaceutical combination therapy currently in clinical development for patients with advanced solid tumors, including hormone receptor-positive (HR+)/HER2-negative advanced breast cancer, harboring activating mutations in the PI3Kα (PIK3CA) gene. - **ETX-636** is a novel, orally bioavailable, allosteric, pan-mutant-selective inhibitor and degrader of PI3Kα, with high selectivity for multiple activating mutant forms while sparing wildtype PI3Kα. This dual mechanism (inhibition and proteasome-dependent degradation) leads to deep and durable pathway inhibition and has demonstrated robust anti-tumor activity without disrupting glucose metabolism, a common toxicity associated with non-selective PI3Kα inhibitors[1][2][3][8][9]. - **Fulvestrant** is a selective estrogen receptor degrader (SERD) approved for advanced HR+ breast cancer. The combination is being evaluated in first-in-human Phase 1/2 clinical trials to assess safety, tolerability, pharmacokinetics, pharmacodynamics, and anti-tumor activity[4][5][6][7][10].