Savolitinib Demonstrates Significant Survival Benefits in MET Exon 14 Skipping NSCLC Across Overall and Key Subgroups Including PSC and Brain Metastases

Shanghai, March 31, 2022 /PRNewswire/ -- The 2022 European Lung Cancer Congress (ELCC) officially announced on March 30 local timeAstraZeneca and HUTCHMED's jointly developed Orpathia^®(General Name: Savolitinib)Final Overall Survival (OS) Results and Subgroup Analysis for the Treatment of Adult Patients with Locally Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC) Harboring Mesenchymal-Epithelial Transition Factor (MET) Exon 14 Skipping Alterations, Who Have Disease Progression or Are Intolerant to Standard Platinum-Based Chemotherapy After Platinum-Based Chemotherapy. The published results showed that savolitinib achieved a median overall survival (mOS) of 12.5 months in the overall population with MET exon 14 skipping mutations, with a favorable safety profile, and demonstrated significant survival benefits in subgroups such as pulmonary sarcomatoid carcinoma (PSC), previously treated patients, and those with brain metastases.^[1]。

The number of lung cancer patients in China accounts for more than one-third of the total number of lung cancer patients worldwide, and the incidence of MET exon 14 skipping mutations in NSCLC is approximately 2%-3%. This mutation is a targeted mutation of the MET gene.^[2]-[3][4]Previous clinical study results showed that the median OS was only 6.7 months for lung cancer patients with MET exon 14 skipping who received first-line chemotherapy, indicating a poor prognosis.^[5]. In addition, this mutation is more common in PSC (13%-22%), which is a rare and aggressive NSCLC subtype, accounting for 0.3%-3% of all malignant lung tumors.^[6]Compared with other NSCLC subtypes, PSC patients have a poorer prognosis, limited treatment options, and are insensitive to traditional chemotherapy.^[7]-[8][9]. Advanced PSC has low responsiveness to radiotherapy and is resistant to multiple chemotherapeutic drugs, with a low treatment efficacy rate. The mOS after chemotherapy is only about 4 to 8 months.^{[10]-[11][12][13]}。

Savolitinib, with the positive results achieved in the NCT02897479 Phase II single-arm clinical study conducted in China, has changed the clinical practice for MET exon 14 skipping mutations and became available in China in 2021.The FirstApproved targeted drug for MET exon 14 skipping mutations. The clinical data released this time show that the survival benefit of the total population tested with savolitinib is significant, with mOS reaching 12.5 months, and it takes effect very quickly, with a median response time (TTR) of only 1.4 months. The tumor response rate is very high, and the disease control rate (DCR) reaches 91.9%. In addition, savolitinib is currently the only...^*1MET inhibitors with PSC subgroup data achieved an mOS of 10.6 months, an objective response rate (ORR) of 50%, and a disease control rate (DCR) of 90% in the PSC population, showing significant tumor responses and a consistent trend of benefit.^[1]。

In the subgroup of previously treated patients, savolitinib achieved an mOS of 19.4 months, and its ORR in previously treated patients was the highest to date at 52.6%, demonstrating a very significant survival benefit; meanwhile, studies have shown that savolitinib has sufficient brain penetration capability and is currently the only one.^*2A MET inhibitor observed in OS data for brain metastasis populations demonstrates the best tumor response currently seen in brain metastasis populations: ORR of 64.3%, DCR of 100%, median progression-free survival (mPFS) of 7 months in treated brain metastasis patients, and mOS reaching 17.7 months, showing significant survival benefits.^[1], providing a treatment option for this subgroup of patients with poor prognosis and few treatment choices.^[14]。

The Phase II registrational study of Savolitinib included 100% Chinese patient population, enrolling NSCLC patients with MET exon 14 skipping mutations. Among them, 36% were PSC patients, and 21% were patients with brain metastases. The study population had complex characteristics, but both the overall population and each subgroup demonstrated clinically meaningful and significant survival benefits. Additionally, the long-term follow-up analysis results revealed that Savolitinib has a good safety profile, with no interstitial lung disease or new adverse event (AE) signals observed. The incidence of AEs was consistent with findings from previous studies.^[1]。

Professor Lu Shun, Director of the Department of Thoracic Surgery at Shanghai Jiao Tong University Affiliated Chest Hospital and Director of the Shanghai Pulmonary Tumor Clinical Medical Center, stated: "Savolitinib is currently the only one in China.^*3Approved as the first innovative selective MET inhibitor independently developed in China and the first to be marketed in China, it provides a new treatment option for Chinese lung cancer patients with MET gene mutations, finally freeing these patients from the dilemma of having "no available treatment." All patients enrolled in the clinical study are from China. Its advantage over existing chemotherapy regimens has changed the treatment landscape for MET gene mutation-positive non-small cell lung cancer, bringing China’s precision treatment for lung cancer to a new level. It also has the potential to become the first innovative lung cancer targeted drug from China to go global. The release of the final overall survival (OS) data and subgroup analysis results once again confirms the excellent efficacy and safety of savolitinib, further strengthening the confidence of Chinese doctors and patients in using savolitinib for treatment. We hope savolitinib can be included in the medical insurance system as soon as possible to benefit Chinese patients with rare target mutations in lung cancer.

As a multinational pharmaceutical company deeply rooted in the Chinese market, AstraZeneca has always adhered to a localized development path. It is committed to continuously deepening cooperation with outstanding local enterprises, enabling domestically innovated drugs to benefit Chinese patients with broader indications, wider coverage, and faster accessibility, upholding the unchanging value of being "patient-centered." In the future, AstraZeneca will also more firmly continue to collaborate with China's local biopharmaceutical companies, expanding multi-pipeline cooperation in the field of lung cancer, and constantly delivering high-quality innovative drugs incubated, developed, and manufactured in China to an even broader global patient population.