An open-label phase Ib study to determine safety and preliminary efficacy of oral Lucitanib (AL3810) in patients with locally advanced or metastatic gastric, hepatocellular, nasopharyngeal carcinoma, malignant biliary, and thymic tumors.

Abstract

e15502 Background: Angiogenesis is an essential prerequisite for tumor growth, invasion and metastasis. Targeting tumor angiogenesis has become a common therapeutic target in clinical work. Lucitanib, an oral tyrosine kinase inhibitor, precisely targets FGFR/VEGFR/PDFGR. In this study, we evaluated the safety profile and preliminary anti-tumor effects of lucitanib in patients with locally advanced or metastatic gastric (GC), hepatocellular (HCC), nasopharyngeal carcinoma (NPC), malignant biliary (MBT) and thymic tumors (TT). Methods: Patients (Pts) with locally advanced or metastatic GC, HCC, NPC, BTC and TT, standard therapy failed, ECOG status ≤1, were enrolled. Total 44 subjects (6 GC, 4 HCC, 10 BTC, 4 TT, 20 NPC) were recruited, then randomized into two groups with lucitanib 10 mg QD given continuously (CON) or intermittently (INT) lucitanib 10 mg QD three weeks on and one week off. Results: 22 pts were included in CON and INT group respectively. The most common drug-related treatment emergent adverse events (TEAEs) for CON (AE≥10%, Grade≥3 ): proteinuria (19 [86.4%], 4 [18.2%]), hypertension (18 [81.8%], 7 [31.8%]), haematuria (3 [13.6%], 0), aspartate aminotransferase increased (8 [36.4%], 1 [4.5%]), hypothyroidism (7 [31.8%], 0), blood creatinine increased (5 [22.7%], 0), platelet count decreased (5 [22.7%], 1[4.5%]), white blood cell count decreased (3 [13.6%], 0), weight decreased (4 [18.2%], 0), diarrhea (4 [18.2%], 0) and rash(6 [27.3%], 0). For INT: proteinuria (8 [36.4%], 1[4.5%]), hypertension (9 [40.9%], 4 [18.2%]), hypothyroidism (6 [27.3%], 0), platelet count decreased (3 [13.6%], 0), white blood cell count decreased (4 [18.2%], 0). Treatment discontinuation due to drug-related TEAEs were 3 pts (13.6%) and 1 pt (4.5%) in CON and INT respectively. Preliminary efficacy for CON: ORR: 13.6%, DCR: 72.7%, median PFS: 3.8 months; for INT: ORR: 4.5%, DCR: 40.9%, median PFS: 1.9 months. Conclusions: Although CON exhibited higher incidence, drug-related TEAEs at both groups were expected and manageable. Lucitanib exhibited better efficacy profile when administrated 10mg QD continuously. Further safety and efficacy of lucitanib is being evaluated in phase II/III studies. Clinical trial information: 03260179.