625O - Efficacy and safety of lucitanib (AL3810) in second or subsequent-line treatment of advanced recurrent or metastatic thymic carcinoma: A randomized, double-blind, placebo-controlled multicenter phase II trial

Background

There are limited treatment options once chemotherapy fails for patients with advanced thymic carcinoma. Lucitanib (AL3810) is a novel orally potent tyrosine kinase inhibitor, selectively targeting FGFR1-3, VEGFR1-3 and PDGFRα/β. This report presents the results of the first randomized, double-blind, placebo-controlled clinical trial (AL3810-202) evaluating efficacy and safety of Lucitanib in patients with advanced recurrent or metastatic thymic carcinoma.

Methods

Patients with advanced recurrent or metastatic thymic carcinoma who have failed at least first-line chemotherapy were randomly assigned (2:1 ratio) to receive Lucitanib 10mg QD (Lucitanib group), or placebo (control group). The primary endpoint was progression-free-survival (PFS) assessed by independent review committee (IRC) using RECIST 1.1.

Results

As of September 6 2021, 68 patients were enrolled, with 46 in Lucitanib group and 22 in control group. Investigator-assessed median PFS was 6.6 months (95%CI: 5.45, 7.49) in Lucitanib group and 1.9 months (95%CI: 0.92, 9.23) in control group (log rank p=0.0306, HR=0.53, 95% CI: 0.29-0.96). IRC assessed median PFS was 5.8 months (95%CI: 4.07, 7.29) in Lucitanib group and 3.7 months (95%CI: 0.99, 7.29) in control group (log rank p=0.1050, HR=0.60, 95% CI: 0.32-1.13). Weighted log rank tests (Modified Peto-Peto, Peto-Peto, Tarone-Ware, Gehan-Breslow) showed statistically significant results (p<0.05) favoring Lucitanib group. Restricted Mean Survival Time analysis showed significantly prolonged PFS benefit in Lucitanib group at week 8, 16, 24, and 32 compared to control group. Bayesian analyses also showed a high posterior probability (96.10%-100%) of Lucitanib group outperforming control group in PFS. The most common grade 3 TRAEs (≥5%) with Lucitanib were hypertension, proteinuria and thrombocytopenia, which are comparable to other similar drugs. No grade 4/5 TRAEs were observed.

Conclusions

This study suggests that Lucitanib may have significant clinical benefit and has acceptable safety for patients with advanced recurrent or metastatic thymic carcinoma.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Haihe Biopharma Co., Ltd., Shanghai, China.

Funding

Haihe Biopharma Co., Ltd., Shanghai, China.

Disclosure

H. Cai, J. Zheng, M. Li, F. Li: Financial Interests, Personal, Full or part-time Employment: Haihe Biopharma Co., Ltd. All other authors have declared no conflicts of interest.