Aveo Quietly Terminates Ficlatuzumab Study

Discontinuation rates are unacceptable

Aveo Oncology has announced the discontinuation of a pivotal phase 2, placebo-controlled study of ficlatuzumab (formerly known as AV-299), a hepatocyte growth factor (HGF) inhibitory antibody that binds to the HGF ligand with high affinity and specificity to inhibit HGF/c-Met biological activities.

A blinded analysis found that patients positive for both vascular endothelial growth factor signaling pathway and epidermal growth factor receptor (EGFR) mutations experienced higher discontinuation rates. This observation significantly compromised the feasibility of the trial, prompting Aveo to pull the plug.

AVEO had entered into a worldwide agreement with Biodesix, Inc., to develop and commercialize ficlatuzumab with VeriStrat, a commercially available serum protein test that helps physicians guide treatment decisions for patients with advanced non–small-cell lung cancer (NSCLC). Under the terms of the agreement, AVEO and Biodesix conducted a proof-of-concept study of ficlatuzumab in combination with erlotinib in advanced NSCLC patients who were selected using BDX001, a serum protein test similar to the VeriStrat test.

HGF is the sole ligand that binds to the c-Met receptor. Activation of the HGF/c-Met pathway is believed to be important in normal processes in embryonic development and wound healing, but its dysregulation is believed to play a role in cancer development, metastasis, and drug resistance.

HGF/c-Met overexpression is observed in many solid tumors, including breast, colorectal, gastric, head-and-neck, lung, and prostate, as well as in hematological malignancies. In addition, c-Met and EGFR are often co-amplified and co-expressed in a variety of tumor types; HGF/c-Met pathway upregulation can render resistance to EGFR-targeted therapies, and vice-versa.

Sources: Reuters; September 12, 2016; and Aveo Oncology; 2016.