Phase II study of danusertib (D) in advanced/metastatic breast and ovarian cancers (BC, OC).

Abstract

5014 Background: D is a small molecule that inhibits a urora kinases, proteins regulating mitosis implicated in tumorigenesis and overexpressed in BC and OC. Methods: In both tumor categories eligible patients (pts) were progressing after 2 prior chemotherapy lines for advanced/metastatic disease; OC pts were resistant or refractory to platinum- based therapy. We evaluated the progression-free rate at 4 months (PFR-4) in a Simon two-stage design. To proceed to the second stage, ≥4 or ≥10 pts free from progression at 4 months were required in BC and OC out of 19 and 24 evaluable pts, respectively. D (500 mg/m2) was administered IV over 24 hours every 14 days. Results: In BC, 42 pts, median age 53 [36-70] years were treated; both stages were completed; 4 pts were not evaluable for efficacy. Seven out of 38 evaluable pts were progression free at 4 months. This result cannot allow to conclude in favor of PFR-4 greater than 20%, set per protocol to define a sufficient activity. Best response was SD in 11 pts (median duration: 20 weeks). In OC, 34 pts, median age 60 [35-76] years, were treated and two withdrew their consent. Twenty-four pts were platinum resistant (50% after primary platinum based CT), and 10 pts platinum refractory (all cases except one after primary platinum based CT). Four pts were free from progression at 4 months and the study was closed after stage 1. Best response was a confirmed PR in 1 pt which lasted 17.3 weeks, and was associated with a partial metabolic response on PET and a drop in CA125 by 80% at 4 months. There were 10 pts with SD. The most frequent grade (G) 3/4 (NCI-CTCAE, version 3.0) hematological toxicity consisted of short lasting neutropenia (86%). G3 lymphocytopenia and thrombocytopenia occurred in 7 and 1 pts, respectively; G 3/4 anemia was noted in 2 pts. The most common non-hematological G3/4 drug-related events were fatigue (10 pts) and febrile neutropenia (5 pts). Diarrhea and pyrexia were noted in 2 pts each. Conclusions: The efficacy of D observed in this trial of third-line treatment of BC and platinum resistant/refractory OC at this dose and regimen did not meet the predefined boundaries of the protocol. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Nerviano Medical Sciences