A Phase II Trial of the WEE1 Inhibitor Adavosertib in SETD2-Altered Advanced Solid Tumor Malignancies (NCI 10170).
Edward B MaldonadoW Kimryn RathmellGeoffrey I ShapiroNaoko TakebeJordi Rodon AhnertDevalingam MahalingamNikolaos A TrikalinosArash Rezazadeh KalebastyMamta ParikhScott A BoernerCelene BalidoGregor KringsTimothy F BurnsEmily K BergslandPamela N MunsterAlan AshworthPatricia M LoRussoRahul R AggarwalPublished in: Cancer research communications (2024)
WEE1 inhibition with adavosertib monotherapy demonstrated limited clinical activity in patients with SETD2-altered solid tumors despite compelling preclinical data indicating a synthetic lethal effect, which did not translate into robust tumor regression. Loss of the H3K36me3 trimethylation mark caused by SETD2-deficiency was confirmed in the majority of evaluable tumors. A subset of patients derived clinical benefit as manifested by minor tumor regressions and prolonged SD.