AstraZeneca (AZ) has started phase III trials of savolitinib, a drug for a rare form of kidney cancer, in partnership with its original developer Hutchison China MediTech (Chi-Med).
The start of the late-stage trials programme triggers a $5m payment from AZ to the Hong Kong-based biotech company, which is listed on the London Stock Exchange, and marks a key milestone in Chi-Med’s efforts to develop a range of oral cancer drugs for international markets. AZ licensed rights to savolitinib in 2011.
The SAVOIR trial will compare savolitinib to Pfizer’s marketed RCC drug Sutent (sunitinib) in patients with papillary renal cell carcinoma (PRCC) whose tumours are driven by the c-MET cancer-associated mutation, and is billed as the first to test a molecularly-targeted therapy in PRCC. It is intended to support marketing applications for savolitinib in Europe and the US, according to Chi-Med.
More than 80% of RCC tumours originate in clear cells – found in the epithelial cells lining the kidney. PRCC is the most common form of non-clear cell RCC, accounting for around 10-15% of all cases and the c-MET pathway is thought to be an important driver in most cases of PRCC.
Savolitinib is at the forefront of an effort to develop more effective treatment strategies that are moving towards a “precision medicine” approach to PRCC.
Phase II results with savolitinib in 109 PRCC patients have just been published in the Journal of Clinical Oncology, with around 40% those recruited having c-MET-driven tumours, 40% c-MET-independent and 20% with unknown c-MET status.
Response to the drug was strongly associated with c-MET status, with median progression-free survival (PFS) more than six months in c-MET-driven disease versus 1.4 months in c-MET-independent disease.
“Based on the results of our phase II study, we believe savolitinib has the potential to bring meaningful clinical benefit to patients with c-MET-driven PRCC,” said Christian Hogg, Chi-Med’s chief executive. He noted that the company has developed a companion diagnostic that will be used to select patients for its phase III programme.
Meanwhile, savolitinib is also being tested in combination with AZ’s pair of immuno-oncology drugs – recently-approved PD-L1 inhibitor Imfinzi (durvalumab) and CTLA4 inhibitor tremelimumab – in the CALYPSO trial involving a broader population of patients with metastatic RCC.
The two partners have various other combination studies ongoing, including one pairing savolitinib with AZ’s third-generation EGFR inhibitor Tagrisso (osimertinib) in patients with EGFR-positive advanced lung cancer.