Savolitinib Plus Osimertinib Receives Priority Review in China for Pretreated EGFR+ NSCLC With a MET Amplification

Savolitinib Plus Osimertinib for Pretreated

EGFR+ NSCLC | Image Credit: © Axel Kock

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China’s National Medical Products Administration (NMPA) has granted priority review to a new drug application (NDA) seeking the approval of savolitinib (Orpathys) in combination with osimertinib (Tagrisso) for the treatment of patients with locally advanced or metastatic EGFR-mutated non–small cell lung cancer (NSCLC) harboring a MET amplification following disease progression on first-line EGFR inhibitor therapy.¹

The NDA is supported by data from the phase 3 SACHI trial (NCT05015608), which evaluated the potent, highly selective MET inhibitor savolitinib in combination with osimertinib vs platinum-based chemotherapy in this patient population. The study’s independent data monitoring committee deemed that the trial met its predefined progression-free survival (PFS) primary end point at an interim analysis, ending enrollment in the study.

Full data from SACHI will be submitted for presentation at an upcoming medical conference.

“This marks the first regulatory filing for the [savolitinib] and [osimertinib] combination. The combination has demonstrated clear evidence to address MET-driven EGFR inhibitor resistance and offers a continued path for oral treatment,” Michael Shi, MD, PhD, head of R&D and chief medical officer of HUTCHMED, stated in a news release. “With our biomarker-specific approach, we are hopeful to enhance treatment continuity and quality of life for [patients with] NSCLC navigating this challenging journey…we hope to bring this all-oral, chemotherapy-free treatment option to patients with MET-driven lung cancer in the near future.”

The multicenter, controlled, open-label SACHI trial enrolled patients 18 to 75 years of age with histologically or cytologically confirmed, locally advanced or metastatic, stage IIIB, IIIC, or IV NSCLC that was unresectable and unsuitable for radical concurrent chemoradiotherapy.² Patients were required to have disease that harbored sensitive EGFR mutations prior to receiving first-line therapy with an EGFR TKI, and a MET amplification following disease progression on first-line therapy was also necessary. Other key inclusion criteria consisted of measurable lesions per RECIST 1.1 criteria; an ECOG performance status of 0 or 1; a life expectancy of more than 12 weeks; and adequate bone marrow reserve or organ function.

Patients were excluded if they harbored EGFR exon 20 T790M mutations; previously received MET-directed therapy; received prior systemic therapy other than an EGFR TKI for advanced NSCLC; received potent CYP3A4 inducers or CYP1A2 inhibitors within 2 weeks of study treatment; had meningeal metastases, spinal cord compression, or active brain metastases prior to the start of study treatment; or had a history of interstitial lung disease (ILD), drug-induced ILD, radiation pneumonitis, and any active ILD.

Enrolled patients were randomly assigned to receive oral savolitinib once per day plus oral osimertinib once per day in 21-day cycles until disease progression, death, adverse effects leading to discontinuation, or withdrawal of consent; or pemetrexed in combination with platinum-based chemotherapy, which could be cisplatin or carboplatin.^1,2

Along with the primary end point of investigator-assessed PFS, secondary end points included objective response rate, disease control rate, duration of response, overall survival, time to response, independent review committee–assessed PFS, and safety.²

Previously in December 2024, the NMPA granted breakthrough therapy designation to the combination of savolitinib and osimertinib for patients with locally advanced or metastatic EGFR-mutated NSCLC harboring a MET amplification following disease progression on first-line EGFR inhibitor therapy.¹

References

1. HUTCHMED Announces NDA acceptance in China with priority review status for Orpathys and Tagrisso combination in lung cancer patients with MET amplification after progression on first-line EGFR inhibitor therapy. News release. HUTCHMED. January 2, 2025. Accessed January 2, 2025. https://www.hutch-med.com/orpathys-tagrisso-nda-acceptance-in-china-with-priority-review-status-for-lung-cancer-after-egfri/
2. Study on savolitinib combined with osimertinib in treatment of advanced NSCLC with MET amplification (SACHI). ClinicalTrials.gov. Updated March 30, 2023. Accessed January 2, 2025. https://clinicaltrials.gov/study/NCT05015608