China NMPA Approves Savolitinib Plus Osimertinib for EGFR-Mutant, MET-Amplified NSCLC

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China’s National Medical Products Administration (NMPA) has approved the combination of savolitinib (Orpathys) and osimertinib (Tagrisso) for the treatment of patients with locally advanced or metastatic, EGFR-mutated, nonsquamous non–small cell lung cancer (NSCLC) harboring a MET amplification, following disease progression on prior EGFR TKI therapy.1

This regulatory approval was supported by findings from the phase 3 SACHI trial (NCT05015608). Findings presented at the 2025 ASCO Annual Meeting demonstrated that the combination yielded a clinically meaningful improvement in median progression-free survival (PFS), overall response rate (ORR), and duration of response (DOR) compared with standard chemotherapy.

In the intent-to-treat population, the median PFS was 8.2 months (95% CI, 6.9-11.2) with the combination vs 4.5 months (95% CI, 3.0-5.4) with chemotherapy (HR, 0.34; 95% CI, 0.23-0.49; P < .0001).2 Among patients previously treated with a third-generation EGFR TKI, the median PFS was 6.9 months (95% CI, 4.2-9.7) with the combination (n = 37) vs 3.0 months (95% CI, 2.7-4.6) with chemotherapy (n = 37; HR, 0.32; 95% CI, 0.18-0.58; P < .0001). The ORR in the intent-to-treat population was 58% (95% CI, 49%-68% vs 34% (95% CI, 25%-44%), respectively, and the respective disease control rates (DCRs) were 89% (95% CI, 81%-94%) vs 67% (95% CI, 57%-76%). The median DOR was 8.4 months (95% CI, 5.9-11.1) vs 3.2 months (95% CI, 2.8-4.2), respectively.

“The approval of the [savolitinib] and [osimertinib] combination is a significant milestone in addressing the complex challenges of lung cancer treatment in China, where the EGFR mutation is common amongst [patients with] NSCLC,” Shun Lu, MD, PhD, chief of the Shanghai Lung Cancer Center at Shanghai Chest Hospital, School of Medicine, Shanghai Jiaotong University in China, stated in a news release,1 “For patients who develop MET amplification after progressing on EGFR inhibitors, the combination offers a continued all-oral, chemotherapy-free approach to tackle a critical resistance mechanism. As a researcher and clinician, I am excited about the opportunity to offer this targeted therapy to patients, improving their treatment outcomes and quality of life through innovative research.”

SACHI Trial Breakdown

The randomized, open-label, multicenter phase 3 SACHI study enrolled patients with unresectable or metastatic NSCLC who had progressed on first-line EGFR TKI therapy and exhibited centrally confirmed MET amplification.2 Eligible patients were required to have an ECOG performance status of 0 or 1. Along with an acquired MET amplification following either a first- or second-generation TKI could not also have an EGFR T790M mutation; those who received a prior third-generation EGFR TKI only needed MET amplification.

Patients were randomly assigned 1:1 to receive savolitinib at 600 mg once per day for patients weighing at least 50 kg or 400 mg per day for those under 50 kg in combination with osimertinib at 80 mg once per day; or platinum plus pemetrexed chemotherapy for 4 to 6 cycles followed by pemetrexed maintenance. Treatment continued until disease progression or the development of intolerable toxicity. Patients in the chemotherapy arm were permitted to cross over to the combination arm upon confirmation of progressive disease by an independent review committee (IRC).

Stratification factors included brain metastases (yes vs no), prior exposure to third-generation EGFR TKI (yes vs no), and EGFR mutation subtype (exon 19 deletion vs L858R insertion mutation vs others).

The primary end point of the trial was PFS by investigator assessment, and key secondary end points included PFS by IRC, ORR, DCR, DOR, time to response (TTR), overall survival (OS), and safety.

Survival Analysis Continued

Subgroup analyses showed consistent PFS benefit regardless of brain metastasis status. Among patients with a history of brain metastases, the median PFS was 6.9 months with savolitinib/osimertinib vs 4.7 months with chemotherapy (HR, 0.40; 95% CI, 0.23-0.71; P = .0011). In patients without brain metastases, median PFS was 9.6 months vs 4.2 months, respectively (HR, 0.30; 95% CI, 0.18-0.48; P < .0001).

OS data were immature at the time of the analysis, with 40% maturity. The median OS was 22.9 months (95% CI, 16.8-not evaluable) in the savolitinib/osimertinib group vs 17.7 months (95% CI, 14.9-26.3) in the chemotherapy arm (HR, 0.84; 95% CI, 0.55-1.29). Notably, 52% of patients in the chemotherapy group received subsequent treatment with a MET inhibitor, including 45 who crossed over and 10 who received other MET-directed therapies.

Safety Profile

Among patients treated with savolitinib and osimertinib (n = 106), the most frequently observed AEs of any grade included decreased white blood cell count (49%), nausea (48%), vomiting (44%), anemia (41%), and decreased neutrophil count (41%). Other notable AEs in this cohort included hypoalbuminemia (38%), decreased appetite (37%), peripheral edema (36%), and decreased platelet count (33%).

Hepatotoxicity-related laboratory abnormalities were also noted, with 28% of patients experiencing increased alanine aminotransferase levels and 28% experiencing increased aspartate aminotransferase levels. Additionally, 25% had increased blood creatinine levels, and 24% experienced pyrexia.

Compared with the chemotherapy group, patients receiving savolitinib plus osimertinib generally experienced lower rates of hematologic toxicities. For example, anemia occurred in 41% of patients vs 73%, neutropenia was reported in 41% of patients vs 59%, and thrombocytopenia occurred in 33% vs 46%, respectively.

“The NMPA approval marks an important step forward in our mission to address MET-driven progression following first-line EGFR-inhibitor therapy in [patients with] NSCLC.” Weiguo Su, PhD, chief executive officer and chief scientific officer of HUTCHMED, stated in a news release.1 “Our collaboration with AstraZeneca, built on a shared vision to transform oncology care, has been crucial in reaching this achievement. We are committed to advancing this partnership, continuing our research into further treatment settings, and bringing this innovative combination to patients in China and beyond.”

References

1. HUTCHMED announces China approval for Orpathys in combination with Tagrisso for the treatment of lung cancer patients with MET amplification after progression on first-line EGFR inhibitor therapy. News Release. HUTCHMED. June 30, 2025. Accessed June 30, 2025. https://www.hutch-med.com/china-approval-for-orpathys-plus-tagrisso-for-lung-cancer-with-met-amplification-after-1l-egfr-inhibitor/
2. Lu S, Wang J, Yang N, et al. Savolitinib (Savo) combined with osimertinib (osi) versus chemotherapy (chemo) in EGFR-mutant (EGFRm) and MET -amplification ( MET amp) advanced NSCLC after disease progression (PD) on EGFR tyrosine kinase inhibitor (TKI): Results from a randomized phase 3 SACHI study. J Clin Oncol. 2025;43(suppl 17):LBA8505.doi:10.1200/jco.2025.43.17_suppl.LBA8505