A. Varkaris, A. Italiano, S. Sammons, E. Felip Falgas, A. Schram, B. Pistilli, A. Schott, P. Tolosa Ortega, K. Wisinski, M. Wei, R. Nanda, J.E. McGuinness, J. Rodon Ahnert, S. Ehsani, J.J. Liu, A. Timm, J. Shen, E.L. Kwak, C. Saura Manich, G. Curigliano
Oncogenic PIK3CA mutations activate PI3Kα in ∼40% of HR+/HER2- BC and define a validated therapeutic target. Approved PI3K inhibitors target the orthosteric site shared by mutant and WT PI3Kα, causing WT-associated toxicities such as hyperglycemia, rash, diarrhea, and stomatitis. Zovegalisib (zovega, RLY-2608) is an allosteric pan-mutant selective inhibitor that targets mutant forms of PI3Kα while sparing WT. The ReDiscover FIH trial studied zovega with standard-dose fulvestrant (F) in CDK4/6 inhibitor (i)-experienced pts with PIK3CAm HR+/HER2- ABC and defined 600 mg BID fasted as the recommended phase 2 dose (RP2D).