744P - Early Data from a Phase I Study of Nintedanib (BIBF 1120) in Asian Patients with advanced Hepatocellular Carcinoma

Abstract

ABSTRACT Background Nintedanib is an oral, triple angiokinase inhibitor targeting VEGFRs, PDGFRs and FGFRs. This multicentre, open-label, phase I/randomised phase II study (NCT00987935; phase II ongoing) evaluated the efficacy, safety and pharmacokinetics of nintedanib versus sorafenib in patients (pts) with advanced hepatocellular carcinoma (HCC) from Asia, where HCC is endemic and has unique clinical features. Phase I data are presented. Methods Phase I pts had histologically, cytologically or clinically confirmed HCC, ECOG performance status ≤2, Child-Pugh (CP) score ≤7, and ≤1 line of prior systemic therapy. Using a 3 + 3 design, pts were stratified into two groups by liver function and CP score: (I) AST and ALT ≤2 x upper limit of normal (ULN), and CP 5–6; (II) AST or ALT >2 x to ≤5 x ULN, or CP 7. Nintedanib (given continuously in 28-day courses) was started at 50mg bid (group II) or 100mg bid (group I) and increased in 50mg bid increments up to 200mg bid. Therapy was continued until no clinical benefit or undue toxicity. The phase I primary endpoint was the maximum-tolerated dose (MTD) of nintedanib. Results Overall, 35 pts have received nintedanib: 11 in group I(100/150/200 mg bid, n = 4/3/4; median [range] duration: 140 [10–337] days) and 24 in group II (50/100/150/200 mg bid, n = 3/7/3/11; median [range] duration: 81 [2–587] days). In group I, no dose-limiting toxicities (DLTs) were seen at any dose during the first course. In group II, one pt experienced a DLT (CTCAE Grade [G] 3 AST increase) at 100 mg bid in Course 1 (dose-escalation phase). The MTD of nintedanib was thus 200 mg bid in both groups. DLTs seen after MTD assessment were G4 gastrointestinal (GI) haemorrhage/anaemia (50 mg bid), G3 ALT increase (150 mg bid), G3 GI haemorrhage (150 mg bid), G3 hypertension (200 mg bid; n = 2) and G4 gastric ulcer (200 mg bid). The most common adverse events, by system organ class, were GI (83%) and general/administration site disorders (51%), and investigations (51%). Hypertension and rash (any grade) occurred in 6 and 8 pts, respectively. Conclusions Nintedanib has an acceptable safety profile in this Asian HCC population. As in other cancer types and European HCC pts, the MTD of nintedanib was 200 mg bid. Disclosure C. Yen: Chia-Jui Yen: research funding from Boehringer Ingelheim. Y. Shen: Ying-Chun Shen: research funding from Boehringer Ingelheim. H. Shiah: Her-Shyong Shiah: research funding from Boehringer Ingelheim. J. Chen: Jo-Pai Chen: research funding from Boehringer Ingelheim. C. Hsu: Chiun Hsu: research funding from Boehringer Ingelheim. C. Hsu: Chih-Hung Hsu: research funding from Boehringer Ingelheim. D.C. Huang: Dennis Chin-Lun Huang: employee of Boehringer Ingelheim. J. Hocke: Julia Hocke: employee of Boehringer Ingelheim. W. Su: Wu-Chou Su: research funding from Boehringer Ingelheim. A. Cheng: Ann-Lii Cheng: research funding from Boehringer Ingelheim.