Phase Ib Study Of Gedatolisib In Combination With Palbociclib And Endocrine Therapy (Et) In Women With Estrogen Receptor (Er) Positive (+) Metastatic Breast Cancer (Mbc) (B2151009)

1040Background: The majority of women with ER+ MBC develop resistance to ET. ET plus a CDK4/6 inhibitor (CDKi 4/6) demonstrate improved progression-free survival (PFS) in first/later line MBC. Preclinical evidence in PI3K mutant cell-line xenografts (PIK3CA) supported developing a triplet combination of gedatolisib (G), a dual inhibitor of PI3K/mammalian target of rapamycin (mTOR), with CDKi 4/6 palbociclib (P)+letrozole (L) or fulvestrant (F) for patients (pts) with ER+/HER2- MBC. Methods: This ongoing dose escalation/expansion study in pts with ER+/HER2- MBC, in first/later line MBC, evaluates dose-limiting toxicities/recommended phase 2 dose (DLTs/RP2D) for triplet regimens of G+P+L or G+P+F. A 3-arm expansion investigates objective response rate (ORR) compared to historical controls of Arm A) G+P+L in first-line, B) G+P+F in pts with no prior CDKi 4/6 in second-line and C) G+P+F in pts with prior CDKi 4/6. Pts receive G (180 mg IV/week) combined with P+L or P+F at standard of care doses. Secondary end...