740P - Phase I Study of Nintedanib (BIBF 1120) in European Patients with advanced Hepatocellular Carcinoma

Abstract

ABSTRACT Background Caucasian and Asian patients (pts) with hepatocellular carcinoma (HCC) tolerate anticancer drugs differently. This open-label, multicentre, phase I/randomised phase II study (NCT01004003; phase II in progress) evaluated the efficacy, safety and pharmacokinetics of nintedanib (a triple angiokinase inhibitor targeting VEGFRs, PDGFRs and FGFRs) versus sorafenib in pts with advanced HCC from Europe. Initial phase I results are reported. Methods Pts (ECOG performance status ≤2, Child-Pugh [CP] score ≤7) with histologically/cytologically confirmed HCC and no prior systemic therapy were enrolled in the phase I trial and stratified into two groups: (I) AST and ALT ≤2 x upper limit of normal (ULN), and CP 5–6; (II) AST or ALT >2 to ≤5 x ULN, or CP 7. Utilising a 3 + 3 design, cohorts received oral nintedanib continuously in 28-day courses, starting at 50mg bid (group II) or 100mg bid (group I) and escalating up to 200mg bid in 50mg bid intervals. Therapy was continued until no clinical benefit or undue toxicity. The phase I primary endpoint was the maximum tolerated dose (MTD) of nintedanib in Course 1. Results A total of 28 pts (71% Caucasian) have been treated: 13 in group I (median [range] days: 345 [2–757]; 100/150/200mg bid, n = 6/3/4) and 15 in group II (median [range] days: 74 [17–428]; 50/100/150/200mg bid, n = 3/4/4/4). No dose-limiting toxicities (DLTs) were seen in group I or II during Course 1 at doses up to 200mg bid, which was the MTD of nintedanib. After the dose-escalation phase and determination of MTD, seven pts reported DLTs at various dose levels (CTCAE Grade [G]3 bilirubin increase, G3 AST increase, G4 amylase increase, G3 hypertension/ALP increase, G3 amylase increase, G5 multi-organ failure, G3 bilirubin increase). The most frequent adverse events (AEs) in both groups, by system organ class, were gastrointestinal (89%) and general/administration site (39%) disorders. Class-related AEs (any grade) were uncommon (hypertension [n = 2], rash [n = 3]). Hepatic enzyme data will be presented. Conclusions Nintedanib has an acceptable safety profile in pts with advanced HCC at the same dose used in other cancers (200 mg bid). Disclosure D. Palmer: Daniel Palmer: research funding from Boehringer Ingelheim. A.B. Loembe: Arsene-Bienvenu Loembe: employee of Boehringer Ingelheim. M. Studeny: Matus Studeny: employee of Boehringer Ingelheim. J. Hocke: Julia Hocke: employee of Boehringer Ingelheim. T. Meyer: Tim Meyer: research funding from Boehringer Ingelheim