A Phase I-Ii Study To Evaluate Safety And Efficacy Of The Combination Of Niraparib Plus Cabozantinib In Patients With Advanced Kidney/Urothelial Carcinoma.

JOURNAL OF CLINICAL ONCOLOGY(2019)

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摘要
TPS501Background: Niraparib (N) is an orally selective poly(ADP-ribose) polymerase (PARP)-1/-2 inhibitor approved for maintenance treatment of patients (pt) with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer after complete or partial response to platinum-based chemotherapy (CT). Cabozantinib (C) is a tyrosine kinase (TK) inhibitor with activity against TKs including VEGFR2, MET and AXL, approved on kidney cancer pt after TK failure, that has demonstrated clinical activity in heavily pretreated, advanced UC pt. c-Met receptor TK is activated in urothelial carcinoma (UC) cells. c-Met activity can decrease response to PARP inhibitors, whereas treatment with c-Met inhibitors renders cells more sensitive to PARP inhibition. UC pt with tumors overexpressing c-Met may benefit from the combination of c-Met and PARP inhibitors. This multicenter, open-label phase (ph) I-II study is to explore the maximum-tolerated dose (MTD) of N + C combination in pt with advanced genitourinary maligna...
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