Phase I study of danusertib (D) in combination with bevacizumab (B) in solid tumors.

3066 Background: D is a small molecule that inhibits Aurora Kinases, proteins regulating mitosis and overexpressed in many tumors. Investigation of the combination is based on additive effect of the drugs in preclinical models, their different mechanism of action and non-overlapping toxicity profiles. Methods: Objectives: to define first cycle (C) dose limiting toxicities (DLTs) and thereby the recommended phase 2 dose (RP2D), safety, PK profiles and antitumor activity. Cohorts of 3-6 pts were sequentially allotted to dose levels (DL) 1, 2, 3 of D (190, 250, 330 mg/m2, respectively, on days [d] 1 and 8) and fixed dose of B (15 mg/kg, on d1) given IV every 3 weeks. DLTs were defined as grade 4 neutropenia (G4 ANC) for >7d, febrile neutropenia (FN), neutropenic infection, G4 thrombocytopenia (PLT), G3 PLT for >7d or with bleeding, any G3/4 non-hematologic toxicities, failure to administer 80% of D in C1, >2 week-delay in starting C2. Results: 20 pts (10 males), median age 54 [22-70] were treated. Primary tu...