RESULTS published from a Phase II clinical trial have shown the potential of the investigational drug savolitinib in the treatment of c-MET-driven papillary renal cell carcinoma. Renal cell cancer is the most common type of kidney cancer and papillary renal cell carcinoma is the second most histologic subtype. This subtype is linked with c-MET gene alternations; currently both c-MET and its ligand, hepatocyte growth factor, have been found to be a key factor in the underlying molecular events leading to cancer formation in papillary renal cell carcinoma.
Papillary renal cell carcinoma is challenging to treat, with currently available therapies for renal cell carcinoma only resulting in a modest improvement. Furthermore there are no approved therapies for the direct treatment of c-MET-driven papillary renal cell carcinoma, hence the pertinence of this clinical trial investigating savolitinib.
This Phase II trial was carried out at 22 sites across the UK, USA, Spain, and Canada. Patients in the study had papillary renal cell carcinoma at the locally advanced or metastatic stage. Overall, 109 patients were treated with ≥1 dose of savolitinib. Of these patients, papillary renal carcinoma was c-MET-driven in 44, c-MET-independent in 46, and the c-MET status of 19 patients was unknown. It was demonstrated that c-MET status was a better predictor of response to savolitinib than classification of papillary renal cell carcinoma based on pathology. The drug was found to selectively inhibit c-MET-driven tumour progression in papillary renal carcinoma patients: 18% of this subgroup achieved a partial response. Furthermore, progression-free survival was greater in patients with c-MET-driven papillary renal cell carcinoma compared with those with c-MET-independent disease, at 6.2 months and 1.4 months, respectively (p<0.0001). Overall, savolitinib treatment was typically tolerated well, with most adverse events being Grade 1 or 2.
Taking the investigation of savolitinib to the next stage, a Phase III study in patients with advanced papillary renal carcinoma is planned to begin enrolling patients later in 2017.