Gedatolisib (pan-PI3K/mTOR) Triplet Hits 85% ORR in HR+/HER2- mBC

Gedatolisib 180 mg IV weekly plus palbociclib and letrozole/fulvestrant was explored in the phase 1b NCT02684032 dose-expansion (four cohorts by prior therapy). ORR reached 85% with 72% 12-mo PFS in treatment-naïve Arm A, 77%/55% after prior ET (Arm B), 36%/24% post-CDK4/6 (Arm C) and 63%/53% in an alternate-schedule post-CDK4/6 arm (Arm D); median OS is still immature. For context, palbociclib + letrozole alone records ≈44% front-line ORR, while real-world alpelisib after CDK4/6 failure delivers ORR ≲13%, highlighting the triplet’s potency across lines.

https://aacrjournals.org/clincancerres/article/31/12_Supplement/P4-08-25/752353/Abstract-P4-08-25-Overall-survival-in-patients