Chi-Med starts phase II study of savolitinib in pulmonary sarcomatoid carcinoma

Savolitinib is a highly selective and potent oral c-Met inhibitor with global first-in-class potential.  The first drug dose was administered on February 10, 2017.

This Phase II study is a multi-center, single-arm, open-label study to evaluate the efficacy and safety of savolitinib as a monotherapy in treating locally advanced or metastatic PSC patients harboring mesenchymal epithelial transition (“Met”) gene alterations. 

The primary endpoint is objective response rate (ORR), with secondary endpoints including progression free survival (PFS), disease control rate (DCR), duration of response (DoR), overall survival (OS) and safety.

PSC is a rare subset of poorly differentiated non-small cell lung cancer (“NSCLC”).  Containing a component with sarcoma-like (spindle and/or giant cell) features, PSC accounts for approximately 0.4% of all cases of lung cancer in the US, according to the Surveillance, Epidemiology and End Results database. 

These tumors are highly aggressive with outcomes significantly worse than other forms of NSCLC, and are more resistant to conventional chemotherapies.  There is no approved targeted therapy for this fatal disease.

The sarcomatoid component of some PSC tumors is believed to derive from carcinoma cells through the activation of Met.  Met gene exon 14 skipping has been reported as one of the major genetic alterations in PSC, acting as a negative control in Met signaling. 

This genetic alteration has been found in approximately 20-30% of PSC patients. As such, a highly selective c-Met inhibitor may provide clinically meaningful benefit to patients with PSC.

Savolitinib is a potential global first-in-class inhibitor of c-Met (also known as mesenchymal epithelial transition factor) receptor tyrosine kinase, an enzyme which has been shown to function abnormally in many types of solid tumors. 

It was developed as a potent and highly selective oral inhibitor specifically designed to address issues observed in the clinic with first-generation c-Met inhibitors, including renal toxicity.