TBCRC028: A phase Ib/II trial of GDC-0941 (a PI3K inhibitor) in combination with cisplatin in metastatic androgen receptor-negative triple-negative breast cancer (TNBC).

Abstract

TPS1148 Background: We recently reported six distinct molecular subtypes of TNBC, including two basal-like subtypes with cell cycle and DNA damage response (DDR) gene expression (GE) signatures (BL1 and BL2) and a luminal androgen receptor (LAR) subtype which expresses AR by immunohistochemistry. BL1 and BL2 cell lines respond to DNA damaging agents, including cisplatin. Consistent with the frequent alterations in DDR and PI3K pathways in TNBC, the combination of cisplatin and the pan-PI3K inhibitor GDC0941 was very active against AR-negative TNBC cell lines in preclinical studies. This trial will evaluate the benefit of the addition of GDC-0941 to cisplatin in patients with metastatic AR-TNBC. Methods: This is an open-label phase Ib/II multiple institution trial in which patients with metastatic AR-TNBC will be randomized to: a) cisplatin 25 mg/m2 on days 1, 8, and 15 of a 28 day cycle, or b) cisplatin with GDC-0941. Biopsy of a metastatic lesion at baseline, at day 5-10, and at progression is required. ...