889P - Phase I Dose-Escalation Study to Determine the Maximum Tolerated Dose (Mtd) of Nintedanib (Bibf 1120) in Combination with Carboplatin/Pegylated Liposomal Doxorubicin (Pld) in Patients (Pts) with Recurrent Ovarian Cancer (Roc)

Abstract

ABSTRACT Aim: Nintedanib (N) is an oral, triple angiokinase inhibitor of VEGF, PDGF and FGF signalling. A recent study showed that the addition of N to standard 1st-line chemotherapy significantly prolongs PFS (HR 0.84; p = 0.0239) in advanced EOC (epithelial ovarian cancer) pts.1 The current study (NCT01314105; 1199.119) was designed to determine dose-limiting toxicities (DLTs) and MTD of N + carboplatin/PLD in pts with ROC. 1Du Bois A, et al. Int J Gynecol Cancer. 2013;23(8suppl 1):abstract p7. Methods: This was a dose-escalation study of oral, continuous daily dosing of N (days 2–28) + iv carboplatin/PLD (AUC 5/30 mg/m2) on day 1 in a 28-day cycle in pts with ≤3 lines of therapy for platinum-sensitive ROC. Cohort 1 received 150 mg bid N, which was the starting dose. The other two predefined cohorts were Cohort -1 (100 mg bid N) and Cohort 2 (200 mg bid N); Cohort -1 was not explored because de-escalation to 100 mg was not necessary. Results: 13 pts (Cohort 1: n = 7, median age 63, EOC n = 7; Cohort 2: n = 6, median age 53, EOC n = 5, fallopian tube carcinoma n = 1) were treated and DLTs were noted in 2 of 12 evaluable pts during the first cycle (Cohort 1: elevated alanine aminotransferase [ALT], 1 pt; Cohort 2: elevated ALT and aspartate aminotransferase [AST], 1 pt). The MTD of N was determined to be 200 mg bid + carboplatin/PLD (AUC 5/30 mg/m2). The most frequent drug-related Grade ≥3 adverse events (AEs) in Cohort 1 were elevated ALT, AST and gamma - glutamyltransferase (GGT) (14.3% each) and in Cohort 2 were elevated ALT (50.0%), AST (33.3%) and GGT (33.3%); neutropenia (33.3%); decreased haemoglobin (16.7%); and diarrhoea (16.7%). The elevated ALT case in Cohort 1 was a serious AE. All CTCAE Grade 3 events were manageable with basic supportive care, temporary treatment interruptions and N dose reductions. Conclusions: The MTD of N was 200 mg bid with carboplatin/PLD (AUC 5/30 mg/m2), and none of the pts discontinued the trial because of safety reasons. This combination exhibited a favourable safety profile with no unexpected AEs in pts with platinum-sensitive ROC. An expansion cohort study of six additional patients treated at the MTD is currently ongoing. Disclosure: A. Ballester: Employee: Boehringer Ingelheim Espana S.A., Spain; M.O. Sailer: Employee: Boehringer Ingelheim Pharma GmbH KG, Germany; M. Merger: Employee: Boehringer Ingelheim Pharma GmbH KG, Germany; N. Morsli: Employee: Boehringer Ingelheim France S.A.S., France. All other authors have declared no conflicts of interest.