Savolitinib (Orpathys), an oral, selective MET TKI, has received conditional approval from China's National Medical Products Administration (NMPA) for the treatment of patients with locally advanced or metastatic gastric cancer or gastroesophageal junction (GC/GEJ) adenocarcinoma harboring MET amplification who have progressed on at least 2 prior lines of systemic therapy.1
The decision marks the first approval of a selective MET inhibitor for this indication in China and represents the third approved indication for savolitinib in the country.
Data from a phase 2 registrational study (NCT04923932) supported the NMPA decision. Findings published in Nature Medicine and presented at the 2026 ASCO Annual Meeting showed that the objective response rate (ORR) per RECIST 1.1 criteria, as assessed by an independent review committee (IRC), was 32.3% (95% CI, 21.2%–45.1%) in the pivotal phase population (n = 65), exceeding the prespecified efficacy threshold.1,2 Additionally, the IRC-assessed disease control rate (DCR) was 63.1% (95% CI, 50.2%–74.7%). The median duration of response (DOR) by IRC was 9.7 months (95% CI, 3.7–18.5). The median time to response (TTR) was 1.4 months.1
Additionally, the median progression-free survival (PFS) with savolitinib by IRC was 4.0 months (95% CI, 2.6–5.0), with a 6-month PFS rate of 28.8% (95% CI, 17.5%–41.2%).2 The median overall survival (OS) was 6.9 months (95% CI, 5.9-8.6).
“This milestone approval marks a critical leap forward for biomarker-driven precision medicine in gastrointestinal oncology,” Lin Shen, MD, vice president of Peking University Cancer Hospital and principal investigator of the phase 2 study, stated in a news release.1 “The clinical data from our pivotal study, recently recognized and published by Nature Medicine, provided compelling evidence that identifying MET amplification through timely molecular testing can directly guide patients to a highly effective, targeted oral option. [Savoltinib’s] entry into the MET-amplified gastric cancer clinical setting offers clinicians a powerful, precise new tool to interrupt this aggressive oncogenic driver.”
MET Its Match: Savolitinib Clears NMPA for MET-Amplified Gastric Cancer
- The NMPA granted conditional approval to savolitinib for MET-amplified GC/GEJ adenocarcinoma based on a pivotal phase 2 trial in which the agent achieved an IRC-assessed ORR of 32.3% (95% CI, 21.2%–45.1%) in the pivotal population (n = 93).
- In the pooled target population (n = 85), the DCR was 68.2% (95% CI, 57.2%–77.9%) and the median DOR was 9.2 months (95% CI, 4.2–23.2), supporting the durability of response with savolitinib monotherapy.
- The safety profile of savolitinib was manageable and consistent with prior MET inhibitor experience, with no treatment-related deaths in the pivotal population.
How was the pivotal phase 2 registrational trial designed?
This single-arm, open-label, phase 2 registrational trial was conducted across sites in China and enrolled adult patients at least 18 years of age with locally advanced or metastatic GC/GEJ adenocarcinoma whose tumors harbored MET amplification and who had received at least 2 prior lines of systemic therapy, including at least one fluoropyrimidine- or platinum-based regimen.2 Patients were required to have an ECOG performance status of 0 or 1, measurable disease per RECIST 1.1 criteria, and adequate organ function. Patients with prior MET-targeted therapy were excluded.
Eligible patients received oral savolitinib at a dose of 600 mg once daily in continuous 21-day cycles until disease progression, unacceptable toxicity, or withdrawal of consent. The primary end point was IRC-assessed ORR per RECIST 1.1 criteria, evaluated against a prespecified null hypothesis ORR of 10% with a target ORR of 25%. Secondary end points included DCR, TTR, DOR, and PFS, all assessed by both IRC and investigator; OS was also evaluated as an exploratory end point.
The data cutoff for the primary analysis supporting the NMPA submission was October 8, 2025.1,2 The median age among patients treated on the study (n = 93) was 62.0 years (range, 34–82), 76.3% were male, and the majority (83.9%) had an ECOG performance status of 1.2 Most patients had gastric primary tumors (74.2%) vs GEJ (25.8%), and 84.9% had previously received 2 lines of prior therapy, with 15.1% having received 3 or more prior lines. Prior therapy included fluoropyrimidine-based (100%), platinum-based (96.8%), taxane-based (68.8%), and anti-HER2 therapy (11.8%) regimens. MET amplification was confirmed centrally in all patients; the median MET/CEP7 ratio was 4.7 (range, 2.0–34.9).
What additional safety data were reported?
Savolitinib was generally well tolerated in the pivotal population (n = 65), and its safety profile was consistent with the agent’s established mechanism of MET inhibition. Treatment-related adverse effects (TRAEs) of any grade occurred in 92.3% of patients. Grade 3 or higher TRAEs were reported in 35.4% of patients, and serious TRAEs occurred in 16.9% of patients. TRAEs leading to interruption or reduction of savolitinib occurred in 32.3% of patients, including dose interruptions in 13.8% and dose reductions in 24.6%. TRAEs leading to permanent discontinuation of savolitinib were reported in 7.7% of pivotal patients. No treatment-related deaths were reported.
References
- HUTCHMED announces NMPA approval for ORPATHYS® for the treatment of gastric cancer patients with MET amplification. News Release. Hutchmed. July 2, 2026. Accessed July 6, 2026. https://www.hutch-med.com/savolitinib-gc-nmpa-approval/
- Peng Z, Liu T, Wang J, et al. A phase 2 pivotal study of savolitinib in patients with MET-amplified gastric cancer or gastroesophageal junction adenocarcinomas. J Clin Oncol. 2026;44(suppl 16):4011. doi:10.1200/JCO.2026.44.16_suppl.4011
