126O - A phase I study evaluating the safety, efficacy, pharmacokinetics and pharmacodynamics of AL3810 in advanced solid tumors

Date 20 December 2015
Event ESMO Asia 2015 Congress
Session Developmental therapeutics
Topics Drug Development
Translational Research
Presenter Athanasios Pallis
Citation Annals of Oncology (2015) 26 (suppl_9): 37-39. 10.1093/annonc/mdv521
Authors J. Cao1, J. Li1, D. Ji1, W. Shen1, L. Jiang2, X. Ma2, J. Pang2, A. Kanehisa3, F. Legrand4, A. Pallis3, G. Paux3, R. Robert3, X. Chen5, P. Letecheur5, L. Qiang5, J. Ding6
  • 1Department Of Medical Oncology, Fudan University Shanghai Cancer Center, 200032 - Shanghai/CN
  • 2Haihe, ShangHai HaiHe pharmaceutical, 201203 - Shanghai/CN
  • 3Iris, Institut de Recherches Internationales Servier, Suresnes/FR
  • 4Pit Oncology, Institut de Recherches Internationales Servier (IRIS), Suresnes, Suresnes/FR
  • 5Ictr, International Centre for Therapeutic Research (Servier), Beijing/CN
  • 6Simm, Shanghai Intsitute of Materia Medica, Shanghai/CN

Abstract

Aim/Background

AL3810 (lucitanib) is a potent, oral tyrosine kinase inhibitor of FGFR1-3, VEGFR1-3 and PDGFRα/ß. These well-described signaling pathways are essential for tumor growth, survival, migration, and angiogenesis. This study aims to evaluate the safety of AL3810 in Chinese patients with advanced solid tumors.

Methods

This phase I, single-center study evaluated the tolerability of oral AL3810 in terms of Maximum Tolerated Dose (MTD), Dose-Limiting Toxicities (DLTs), and aimed to identify the Recommended Dose (RD). A 3 + 3 dose escalating design was used. Initial dose levels to be tested were 10mg, 15mg and 20mg daily on a continuous basis. Moreover, up to 12 patients were to be included at the RD level to confirm the RD based on safety and efficacy evaluation. PK analysis using a non-compartmental PK population modeling approach will be performed.

Results

As of August 2015, 16 patients (pts) were treated with AL3810, 14 were female, median age was 56 yrs (range 28-64) with ECOG 0/1 in 1/15 pts. During the escalation part, 10mg and 15mg dose levels were explored. Two DLTs occurred at 15mg daily dose out of 5 patients (fatigue Gr 3 and direct bilirubin increase Gr 3,). Therefore 15mg dose level was defined as the MTD and 10mg as the RD. Currently, 8 additional pts are enrolled at this dose level to confirm the RD.

Common Gr 2-3 adverse events occurring in ≥ 3pts were hypertension (10 pts), hypothyroidism (9 pts), proteinuria (6 pts), fatigue (3 pts), decreased appetite (3 pts), and white blood cell count decreased (3 pts).

Two pts with metastatic breast cancer, treated at 10mg daily, had a confirmed Partial Response according to RECIST. Disease stabilization of 4 months was observed in pt with ovarian cancer treated at 10 mg.

Conclusions

This phase I trial, testing for first time AL3810 in Chinese patients, identified 15mg daily as the MTD and 10mg as the RD for future studies. Expansion cohorts are planned in different indications.

Clinical trial identification

CL1-8088-005

Disclosure

L. Jiang, X. Ma, J. Pang: employee of HaiHe pharmaceutical. A. Kanehisa, F. Legrand, A. Pallis, G. Paux, R. Robert: employee at Institut de Recherches Internationales Servier (IRIS). X. Chen, P. Letecheur, L. Qiang: employee at ICTR China. J. Ding: employee of SIMM. All other authors have declared no conflicts of interest.