On April 4, 2023 HUTCHMED (China) Limited ("HUTCHMED") (Nasdaq/AIM:HCM; HKEX:13) reported that it has consulted the China National Medical Products Administration ("NMPA") and reached an agreement to initiate the registration phase of the ongoing Phase II trial of HMPL-453 for intrahepatic cholangiocarcinoma ("IHCC") patients with fibroblast growth factor receptors ("FGFR") 2 fusion (Press release, Hutchison China MediTech, APR 4, 2023, View Source [SID1234629797]). If positive, the data from the registration phase may be used to support a future New Drug Application ("NDA") filing. The first patient received their first dose in March 2023.
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In addition, it also reached an agreement to initiate the registration phase of the ongoing Phase II trial of savolitinib for gastric cancer patients with mesenchymal–epithelial transition ("MET") amplification following NMPA consultation. If positive, the data from the registration phase may be used to support a future NDA filing. The first patient also received their first dose in March 2023.
The study of HMPL-453 is a single-arm, multi-center, open-label, Phase II registration study to evaluate the efficacy, safety and pharmacokinetic of HMPL-453 in treating advanced IHCC patients with FGFR2 fusion. Primary endpoint is objective response rate ("ORR"). Secondary endpoints include progression-free survival ("PFS"), disease control rate (DCR), duration of response (DoR) and overall survival (OS). The study is expected to enroll approximately 90 additional patients. Additional details may be found at clinicaltrials.gov using identifier NCT04353375.
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 and esophagogastric junction adenocarcinoma patients with MET amplification. Primary endpoint is ORR evaluated by the Independent Review Committee (IRC) (RECIST 1.1). Secondary endpoints include PFS and incidence of various adverse events (AE). The study is expected to enroll approximately 60 additional patients. Further details may be found at clinicaltrials.gov using identifier NCT04923932.
About HMPL‑453
HMPL‑453 is a novel, highly selective and potent inhibitor targeting FGFR 1, 2 and 3. Aberrant FGFR signaling has been found to be a driving force in tumor growth (through tissue growth and repair), promotion of angiogenesis and resistance to anti-tumor therapies. Abnormal FGFR gene alterations are believed to be the drivers of tumor cell proliferation in several solid tumor settings.
HUTCHMED currently retain all rights to HMPL-453 worldwide.
About IHCC with FGFR2 Fusion
IHCC is one of the subtypes of primary liver cancer. In China, an estimated 61,900 newly diagnosed IHCC occurred in 2015 and the overall IHCC incidence increased by 9.2% per year between 2006 and 2015.[i] FGFR2 fusion has been reported to have a prevalence of 10-15% in IHCC patients.[ii] [iii]
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.
About Gastric Cancer with MET Amplification
MET-driven gastric cancer has a very poor prognosis.[iv] 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.3 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.
It is estimated that MET amplification accounts for approximately 4-6% of gastric cancer patients.[v],[vi] The annual incidence of MET amplification gastric cancer is estimated to be approximately 24,000 in China.