Shanghai: Thursday, June 29, 2017: HMP, a 99.8% subsidiary of Chi-Med, and AstraZeneca today announce that they have initiated a global pivotal Phase III, open-label, randomized multi-center registration study of the highly selective inhibitor of c-MET receptor tyrosine kinase, savolitinib, in c-MET-driven papillary renal cell carcinoma (“PRCC”). This is the first pivotal study ever conducted in c-MET-driven PRCC and the first molecularly selected trial in renal cell carcinoma (“RCC”).
“The launch of the SAVOIR trial, designed to support product registration in the U.S. and Europe, continues to advance our strategy to deliver innovative medicines to major markets worldwide,” said Christian Hogg, Chief Executive Officer of Chi-Med. “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. We also expect to further understand the correlations between c-MET alterations and patient outcomes through epidemiological analyses using our newly developed companion diagnostic assay.”
Susan Galbraith, SVP IMED Oncology, AstraZeneca commented that “It is exciting to achieve this milestone in savolitinib’s development. The data building across our early development studies are encouraging, that savolitinib has the potential to be an important treatment option for c-MET driven cancers including kidney, lung and gastric cancers.”
The initiation of this Phase III trial has triggered a US$5 million milestone payment to HMP from AstraZeneca under the terms of the license and collaboration agreement signed between them in 2011 (as amended).
In addition to SAVOIR, HMP and AstraZeneca are conducting a number of Phase Ib and II studies of savolitinib in kidney cancer, lung cancer and gastric cancer. These studies involve savolitinib as a monotherapy or in combination with other targeted therapy, such as Tagrisso® (osimertinib) or Iressa® (gefitinib). Additional studies combining with Imfinzi® (durvalumab) and Taxotere® (docetaxel) are also in progress.
SAVOIR is a global Phase III, open-label, randomized, controlled trial evaluating the efficacy and safety of savolitinib, compared with sunitinib, in patients with c-MET-driven, unresectable, locally advanced or metastatic PRCC. Approximately 180 patients will be randomized at 50 to 75 sites across five to ten countries. c-MET status is confirmed by the novel targeted next-generation sequencing (NGS) assay developed for savolitinib. Patients will be randomized in a 1:1 ratio to receive either continuous treatment with savolitinib 600 mg (400 mg if <50 kg) orally, once daily, or intermittent treatment with sunitinib 50 mg orally once daily (4 weeks on/2 weeks off), on a 6-week cycle.
The primary objective is to evaluate the primary efficacy endpoint progression free survival (“PFS”) of savolitinib as compared with sunitinib. Secondary endpoints include overall survival, objective response rate (“ORR”), duration of response, best percentage change in tumor size, disease control rate, and safety and tolerability. The impact of savolitinib compared with sunitinib on disease symptoms and quality of life, along with the pharmacokinetics of savolitinib will also be assessed. Additional details about this study may be found at clinicaltrials.gov, using identifier NCT03091192.
Savolitinib (AZD6094/HMPL-504) is a potential first-in-class selective 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 other selective c-MET inhibitors, such as renal toxicity.
Savolitinib was discovered by HMP and is being developed in collaboration with AstraZeneca. Savolitinib is currently being studied in multiple tumor types worldwide including kidney, lung and gastric cancers, both as a monotherapy or in combination with other targeted and immunotherapy agents.
About c-MET-Driven PRCC
Worldwide, about 366,000 new patients are diagnosed with kidney cancer annually. RCC accounts for approximately 80-85% of kidney cancer and has several histological sub-types with different genetic and biochemical characteristics. PRCC is the most common of the non-clear cell renal carcinomas accounting for 10-15% of RCC. However, the biology and molecular characteristics of PRCC are different from those of clear cell RCC (“ccRCC”). Multiple studies indicate that PRCC is c-MET-driven in 40-70% of patients.
There are no therapies approved for patients with PRCC, who currently receive treatments approved for RCC such as sunitinib. These RCC agents were mostly approved on the basis of studies where the majority of subjects were ccRCC patients and where the benefits to the PRCC minority were more modest. Currently the National Comprehensive Cancer Network Guidelines advise PRCC patients to enter clinical trials.
About Savolitinib in PRCC
In February 2017, the results of a global Phase II multicenter study in advanced PRCC was presented at the 2017 American Society of Clinical Oncology Genitourinary Cancers Symposium, which indicated a clear efficacy signal with savolitinib monotherapy in c-MET-driven patients. Median PFS of 6.2 months in c-MET-driven patients as compared with 1.4 months (p<0.0001) in c-MET-independent patients. ORR was 18.2% in c-MET-driven patients vs. 0% (p=0.002) in c-MET independent patients. An encouraging durable response and safety profile were reported in savolitinib treated patients.
Studies of c-MET-driven disease in gastric cancer and lung cancer suggest that c-MET amplification and/or overexpression can be a negative prognostic for disease progression. Over the course of 2017, HMP and AstraZeneca are also conducting a comprehensive molecular epidemiology study of approximately 300 PRCC patient samples to further understand the correlations between c-MET alterations and patient outcomes, including any predictive biomarkers.