HUTCHMED Announces Initiation of SAFFRON Global Phase III Trial in NSCLC with Savolitinib and Osimertinib Combination

On March 7, HUTCHMED announced that it had received a $15 million milestone payment from AstraZeneca. This milestone payment was triggered by the initiation of work on the SAFFRON study.

SAFFRON Study is the first global Phase III study of the combination therapy of Volitinib® (savolitinib) and Tagrisso® (osimertinib) for the treatment of patients with non-small cell lung cancer harboring mesenchymal-epithelial transition factor (MET) amplification and epidermal growth factor receptor (EGFR) mutations. Patient recruitment is expected to begin by mid-2022. The earlier SAVANNAH study provided significant experience for the initiation of the SAFFRON study, and its data are planned to be presented at an upcoming academic conference in the second half of 2022.

To date, AstraZeneca has paid HUTCHMED a total of USD 85 million in upfront, development, and first commercial sale milestone payments under their license and collaboration agreement, out of a total of USD 140 million.

Savolitinib (formerly known as Volitinib) is a potent and highly selective oral MET tyrosine kinase inhibitor that can block the abnormal activation of the MET receptor tyrosine kinase signaling pathway caused by mutations (such as exon 14 skipping mutations or other point mutations) or gene amplification.

Savolitinib was approved for marketing by the NMPA in China in June 2021, for the treatment of patients with non-small cell lung cancer who have MET exon 14 skipping mutations and whose disease has progressed after systemic therapy or who are unable to receive chemotherapy.

After HUTCHMED independently developed and initially advanced savolitinib, AstraZeneca entered into a global licensing and collaboration agreement with them in 2011 to co-develop and promote the commercialization of savolitinib. HUTCHMED leads the clinical development of savolitinib in China and is responsible for its regulatory approval, manufacturing, and supply within the country, while AstraZeneca manages the commercialization in China and leads development and commercialization efforts overseas. In 2012, HUTCHMED submitted the first clinical trial application for savolitinib in China.

"Savolitinib" Project Details

Source: Insight Database (http://db.dxy.cn/v5/home/)

Currently, savolitinib is being developed as a monotherapy or in combination with other drugs for the treatment of various tumor types, including lung cancer, renal cancer, and gastric cancer.

Lung cancer is the leading cause of cancer death in men and women, accounting for approximately one-fifth of all cancer deaths; the number of lung cancer patients in China accounts for more than one-third of the total number of lung cancer patients worldwide. 80-85% of lung cancer patients have non-small cell lung cancer (NSCLC), and most are diagnosed at an advanced stage. Only about 25-30% of patients have the opportunity to undergo surgery at the time of diagnosis. Among those who are eligible for surgery, despite undergoing complete tumor resection and adjuvant chemotherapy, the majority will eventually relapse. In Asian NSCLC patients, the proportion with EGFR mutations is as high as 30%-40%.

MET is a receptor tyrosine kinase. MET amplification or overexpression can occur not only in untreated patients but also represents one of the primary mechanisms of acquired resistance to EGFR TKI therapy in patients with metastatic non-small cell lung cancer harboring EGFR mutations. In newly diagnosed non-small cell lung cancer patients, approximately 2%-3% have MET exon 14 skipping mutations, which are specific genetic alterations.