On August 29, 2023 HUTCHMED (China) Limited ("HUTCHMED") (Nasdaq/AIM:HCM; HKEX:13) reported that the Center for Drug Evaluation of China’s National Medical Products Administration ("NMPA") has granted Breakthrough Therapy Designation ("BTD") to savolitinib for the treatment of locally advanced or metastatic gastric cancer or gastroesophageal junction ("GEJ") adenocarcinoma patients with mesenchymal epithelial transition factor ("MET") amplification who have failed at least two lines of standard therapies (Press release, Hutchison China MediTech, AUG 29, 2023, View Source [SID1234634745]).
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The study of savolitinib is a single-arm, multi-center, open-label, Phase II registration study to evaluate the efficacy, safety and tolerability of savolitinib in treating gastric cancer or GEJ adenocarcinoma patients with MET amplification. Primary endpoint is objective response rate ("ORR") evaluated by the Independent Review Committee ("IRC") (RECIST 1.1). Secondary endpoints include progression free survival (PFS) and incidence of various adverse events (AE), among others. The study is expected to enroll approximately 60 patients. Further details may be found at clinicaltrials.gov using identifier NCT04923932.
About Breakthrough Therapy Designation in China
NMPA grants BTD to new drugs that treat life-threatening diseases or serious conditions for which there are no effective treatment options, and where clinical evidence demonstrates significant advantages over existing therapies. Drug candidates with BTD may be considered for conditional approval and priority review when submitting a New Drug Application ("NDA"). This indicates that the development and review of the therapy for this disease indication may be expedited, to address patients’ unmet needs more quickly.
About Gastric Cancer with MET Amplification
MET-driven gastric cancer has a very poor prognosis.1 The ongoing registration trial follows multiple Phase II studies that have been conducted in Asia to study ORPATHYS in MET-driven gastric cancer patients, including VIKTORY.2 VIKTORY is an investigator initiated Phase II umbrella study in gastric cancer in South Korea in which a total of 715 patients were successfully sequenced into molecular-driven patient groups, including those with MET amplified gastric cancer. Patients whose tumors harbor MET amplification were treated with ORPATHYS monotherapy. The VIKTORY study reported a 50% ORR.
At American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2023 (AACR 2023), it was reported that the interim results from a China Phase II study of savolitinib in patients with MET-amplified GEJ adenocarcinomas or gastric cancer showed a 45% ORR confirmed by IRC and a 50% ORR in patients with high MET gene copy number. Duration of response (DOR) rate at 4-month was 85.7% with median follow up time of 5.5 months. The most common grade≥3 treatment-related adverse events ("TRAE") (≥5%) were platelet count decreased, hypersensitivity, anemia, neutropenia and hepatic function abnormal. Only 1 patient discontinued treatment due to grade 4 liver function abnormal (TRAE) and no patient died due to TRAE.
It is estimated that MET amplification accounts for approximately 4-6% of gastric cancer patients.2,3 The annual incidence of MET amplification gastric cancer is estimated to be approximately 24,000 in China.4
About Savolitinib
Savolitinib is an oral, potent and highly selective MET tyrosine kinase inhibitor that has demonstrated clinical activity in advanced solid tumors. Іt blocks atypical activation of the MET receptor tyrosine kinase pathway that occurs because of mutations (such as exon 14 skipping alterations or other point mutations), gene amplification or protein overexpression.
Savolitinib is marketed in China under the brand name ORPATHYS for the treatment of patients with non-small cell lung cancer ("NSCLC") with MET exon 14 skipping alterations who have progressed following prior systemic therapy or are unable to receive chemotherapy. Іt is currently under clinical development for multiple tumor types, including lung, kidney and gastric cancers, as a single treatment and in combination with other medicines. Starting on March 1, 2023, ORPATHYS was included in the National Reimbursement Drug List (NRDL) for the treatment of locally advanced or metastatic NSCLC adult patients with MET exon 14-skipping alterations who have progressed after or unable to tolerate platinum-based chemotherapy.
Іn 2011, AstraZeneca and HUTCHMED entered a global licensing and collaboration agreement to jointly develop and commercialize savolitinib. Joint development of savolitinib in China is led by HUTCHMED, while AstraZeneca leads development outside of China. HUTCHMED is responsible for the marketing authorization, manufacturing and supply of savolitinib in China. AstraZeneca is responsible for the commercialization of savolitinib in China and worldwide. Sales of savolitinib are recognized by AstraZeneca.