Hengrui initiates a phase III study without proof of concept

Hengrui Medicine (SHSE: 600276) has initiated a pivotal phase III study (CTR20132427) to evaluate the safety and efficacy of apatinib as second-line treatment in patitents with hepatocellular carcinoma (HCC) who had progressed after receiving systemic therapy (e.g., oxaliplatin, arsenious acid) or sorafenib.

Advanced HCC is the third most common cause of cancer death in worldwide. There is a need for second line therapies in patients who had progressed after sorafenib. However, apatinib as second-line treatment in HCC hasn’t yet been tested in clinical study.

In the phase II open-label trial[1], Hengrui tested apatinib in naive patients with HCC. The median time to progression (mTTP) was 4.2 months, and the median overall survival (mOS) was 9.7 months. Apatinib was not superior to sorafenib which demonstrated a mTTP of 5.5 months and a mOS of 10.7 months (12.3 months in Chinese patients[2]).

Apatinib is a selective VEGFR-2 inhibitor derived from vatalanib (PTK787), while sorafenib is a multi-target inhibitor of several protein kinases including VEGFRs, PDGFRs and Raf kinases. It is a high-risk task to demonstrate the efficacy of apatinib in patients who have developed resistance to sorafenib.

Previously, Bristol-Myers Squibb  developed a dual VEGFR/FGFR inhibitor called brivanib (BMS-582664) as second-line treatment for HCC. The phase II results were positive[3], with a disease control rate (DCR) of 45.7%. However, in the phase III trial, brivanib didn’t significantly improve mOS (9.4 vs 8.2 months)[4].

Similarly, Bayer has initiated a phase III trial of regorafenib in patients with sorafenib-pretreated HCC[5]. In the previous phase II study, the mTTP was 4.3 months and the mOS was 13.8 months[6].

[1] J Clin Oncol 32:5s, 2014 (suppl; abstr 4019).

[2] Chinese Journal of Oncology. 2009, 31(1), 58-61.

[3] Clin Cancer Res. 2012, 18(7), 2090-2098.

[4] J Clin Oncol. 2013, 31(28), 3509-3516.

[5] J Clin Oncol 32:5s, 2014 (suppl; abstr TPS4156^)

[6] Eur J Cancer. 2013, 49(16), 3412-3419.

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