Savotinib plus osimertinib receives priority review in China for pretreated EGFR+ NSCLC and MET amplification

The National Medical Products Administration of China (NMPA) has granted priority review to a New Drug Application (NDA) seeking approval of savolitinib in combination with osimertinib/Tagrisso (Osimertinib) for the treatment of locally advanced disease A patient with stage or metastatic EGFR-mutated non-small cell lung cancer (NSCLC) who carries MET amplification after disease progression on first-line treatment with an EGFR inhibitor.

The NDA is supported by data from the SACHI Phase 3 trial (NCT05015608), which evaluated the potent, highly selective MET inhibitor servotinib in combination with osimertinib versus platinum-based chemotherapy in this patient population. The study's independent data monitoring committee concluded that the trial met its prespecified primary endpoint of progression-free survival (PFS) at an interim analysis, ending study enrollment.

This marks the first regulatory filing for the combination of saivotinib and osimertinib. This combination has demonstrated clear evidence of addressing MET-driven resistance to EGFR inhibitors and provides a sustained pathway for oral treatment. Through a biomarker-specific approach, it is expected to improve the treatment continuity and quality of life of NSCLC patients during this challenging journey, bringing this all-oral, chemotherapy-free treatment option to patients with MET-driven lung cancer in the near future.

The multicenter, controlled, open-labelSACHI trial enrolled patients aged 18 to 75 years with histologically or cytologically confirmed locally advanced or metastatic stage IIIB, IIIC or IV non-small cell lung cancer that was unresectable and ineligible for curative concurrent chemoradiotherapy. Patients must have disease harboring a sensitive EGFR mutation before receiving first-line therapy with an EGFR TKI, and MET amplification is necessary after disease progression on first-line therapy. Other key inclusion criteria include measurable disease meeting RECIST 1.1 criteria; ECOG performance status of 0 or 1; life expectancy of more than 12 weeks; and adequate bone marrow reserve or organ function.

Patients were excluded if they carried the EGFR exon 20 T790M mutation; had previously received MET-guided therapy; had received EGFR for advanced non-small cell lung cancer Previous systemic therapy other than TKI; receiving a strong CYP3A4 inducer or CYP1A2 inhibitor within 2 weeks of study treatment; having meningeal metastases, spinal cord compression, or active brain metastases before the start of study treatment; or having a history of interstitial lung disease (ILD), drug-induced ILD, radiation pneumonitis, and any active ILD.

Eligible patients were randomly assigned to receive oral treatment with sivotinib once daily, plus oral osimertinib once every 21 days, until disease progression, death, adverse reactions leading to discontinuation, or withdrawal of consent; or pemetrexed combined with platinum-based chemotherapy, which can be cisplatin or carboplatin. In addition to the primary endpoint of investigator-assessed PFS, secondary endpoints include objective response rate, disease control rate, duration of response, overall survival, time to response, independent review committee-assessed PFS and safety.

Previously, in December 2024, the National Medical Products Administration approved the combination of sivotinib and osimertinib for the treatment of patients with locally advanced or metastatic EGFR-mutated NSCLC carrying MET amplification after disease progression on first-line EGFR inhibitor treatment.

Reference materials:https://www.onclive.com/view/savolitinib-plus-osimertinib-receives-priority-review-in-china-for-pretreated-egfr-nsclc-with-a-met-amplification