1396257-94-5

Ipatasertib is typically efficacious in xenograft models in which Akt is activated because of genetic alterations including PTEN loss, PIK3CA mutations/amplifications, or HER2 overexpression. In these models, tumor growth delay, stasis, or regression is achieved at or below 100 mg/kg daily oral dose, which is the maximum dose tested in immunocompromised mice that is well tolerated. When tested in vivo, daily dosing of Ipatasertib in combination with RP-56976 induces tumor regression and stasis in the PC-3 and MCF7-neo/HER2 xenograft models, at doses where each single agent is ineffective or only causes modest tumor growth delay. Similarly, increased TGI is observed in the OVCAR3 ovarian cancer xenograft model when Ipatasertib is combined with NSC 241240. The combination of Ipatasertib with RP-56976 or NSC 241240 is tolerated with less than 5% body weight loss when compared with treatment with each chemotherapeutic agent alone^[2].