268MO - A phase-Ib study of lucitanib (AL3810) in a cohort of patients with recurrent and metastatic nasopharyngeal carcinoma (NPC)

Background

There remains no standard therapy for patients with multiply pretreated recurrent and metastatic NPC. Overexpression of VEGFR and FGFR is common in NPC and the higher expression is related to poor prognosis. This feature makes NPC potentially suitable for antiangiogenic treatment. AL3810 is a novel multi-target inhibitor of VEGFR1-3, FGFR1-3, and PDGFRα/β. Preliminary data from the phase-Ib, randomized, noncomparative, open label trial are presented showing the safety and efficacy of AL3810 in patients with pretreated recurrent and metastatic NPC.

Methods

Eligible patients were required to have histologically confirmed undifferentiated NPC with measurable lesion according to RECIST 1.1. They had to receive at least 1 prior line of treatment and recurred at locoregional and/or distant sites. All patients were randomized into a continuous (Arm A, 10 mg QD) or intermittent (Arm B, 3 weeks on/1 week off, 10 mg QD) AL3810 dosing arm. The primary endpoint is safety profile. Secondary endpoints include objective response rate (ORR) and disease control rate (DCR).

Results

A total of 20 patients (10 patients in each arm) have been enrolled to date with a median age of 47 years. The median number of prior systemic treatments was 3. The most common drug-related grade 3 or worse TEAEs were hypertension (3/10 in Arm A, 0/10 in Arm B), proteinuria (2/10 in Arm A, 0/10 in Arm B). With appropriate supportive treatment, dose reduction and/or temporary discontinuation, The ≥ grade 3 TEAEs were all manageable. The confirmed ORR was 20% in Arm A, and 10% in Arm B. The DCR was 90% in Arm A vs 60% in Arm B. As of the date of this publication, 2 patients are still receiving AL3810 treatment and one of them in arm A had partial response lasting > 32 months. Detail efficacy outcomes are shown in the below table. Table: 268MO

Conclusions

AL3810 has promising activity and tolerable safety profile in pre-heavily treated NPC. Additional evaluation in a randomized trial with larger sample size is warranted.

Clinical trial identification

NCT03260179.

Editorial acknowledgement

Legal entity responsible for the study

Shanghai HaiHe Pharmaceutical Co., Ltd.

Funding

Shanghai HaiHe Pharmaceutical Co., Ltd.

Disclosure

All authors have declared no conflicts of interest.