Savolitinib Earns Full Approval in China for Locally Advanced/Metastatic MET Exon 14+ NSCLC

China’s National Medical Products Administration (NMPA) has granted full approval to savolitinib (Orpathys) for the treatment of adult patients with locally advanced or metastatic non–small cell lung cancer (NSCLC) harboring MET exon 14 skipping alterations.1

Additionally, the NMPA has converted the prior conditional approval of savolitinib for patients with locally advanced or metastatic NSCLC harboring MET exon 14 skipping alterations whose disease progressed after systemic therapy or were ineligible for chemotherapy to full approval. The initial conditional approval in June 2021 established savolitinib as the first selective MET inhibitor indicated in China for this patient population.

“The approval marks an exciting step forward in addressing the unmet needs of [patients with] NSCLC with MET exon 14 skipping alterations,” Michael Shi, PhD, head of Research and Development and chief medical officer of HUTCHMED, stated in a news release. “It not only validates our research but also emphasizes our dedication to addressing unmet medical needs through targeted drug development. We are focused on advancing our research and expanding access to savolitinib, ultimately improving the treatment landscape for those affected by this challenging form of lung cancer. We also remain committed to further exploring savolitinib in other MET-driven diseases in order to help more patients who may benefit from this targeted treatment.”

Findings from a single-arm, multicenter, confirmatory phase 3b trial (NCT04923945) supported the agent’s full approval. Final study results, which were presented during the 2024 European Lung Cancer Congress, showed that previously untreated patients administered savolitinib (n = 87) achieved an overall response rate (ORR) of 62.1% (95% CI, 51.0%-72.3%) per independent review committee (IRC) assessment.2 The disease control rate (DCR) was 92.0% (95% CI, 84.1%-96.7%), the median duration of response (DOR) was 12.5 months (95% CI, 8.3-15.2), and the median time to response (TTR) was 1.4 months (95% CI, 1.4-1.5). At a median follow-up of 18 months (range, 16.6-19.3), the median progression-free survival (PFS) was 13.7 months (95% CI, 8.5-16.6); the median overall survival (OS) was not reached (NR) at a median follow-up of 20.8 months (range, 19.3-21.6).

In the previously treated patient population (n = 79), the ORR was 39.2% (95% CI, 28.4%-50.9%) per IRC assessment. The DCR was 92.4% (95% CI, 84.2%-97.2%), the median DOR was 11.1 months (95% CI, 6.6-NR), and the median TTR was 1.6 months (95% CI, 1.4-2.7). At a median follow-up of 11 months (range, 8.2-11.2), the median PFS was 11.0 months (95% CI, 8.3-16.6); OS data were not mature at a median follow-up of 12.5 months (range, 11.0-15.4).

Regarding safety, the agent was tolerable, and no new safety signals were observed.1 The most common grade 3 or higher drug-related treatment-emergent adverse effects were abnormal hepatic function (16.9%), increased alanine aminotransferase levels (14.5%), increased aspartate aminotransferase levels (12.0%), peripheral edema (6.0%), and increased gamma-glutamyltransferase levels (6.0%).

“This phase 3b confirmatory study of savolitinib is one of the largest phase 3 clinical trials conducted in China for this patient population to date. Savolitinib has demonstrated clear efficacy and tolerability in both first-line and second-line settings, underscoring its potential as a standard treatment option for [patients with] NSCLC with MET exon 14 skipping alterations,” Shun Lu, MD, PhD, chief of the Shanghai Lung Cancer Center at Shanghai Chest Hospital, School of Medicine, Shanghai Jiaotong University, and a principal investigator of the study, added in the news release. “By making savolitinib available as a first-line treatment, we are able to provide our patients with an effective targeted therapy earlier in their treatment journey. We look forward to introducing this novel treatment and optimizing the treatment strategy for this challenging patient population to improve their outcomes and quality of life.”

Notably, a new drug application (NDA) seeking the approval of savolitinib 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 is under priority review in China as of January 2025.3

“[This] approval reinforces savolitinib as a transformative option for the treatment of biomarker-driven lung cancer, and we are proud that we can now offer this therapy to both first-line and second-line patients in China with advanced NSCLC with MET exon 14 skipping alterations,” Mary Guan, general manager of AstraZeneca China Oncology Business, concluded. “Through our partnership with HUTCHMED, we are advancing savolitinib to address resistance to EGFR TKIs, unlocking new possibilities for treating MET-altered and amplified cancers, and expanding the reach of this innovative therapy to even more patients with this form of lung cancer.”

References

1. HUTCHMED announces NMPA full approval for Orpathys (savolitinib) in China for patients with locally advanced or metastatic MET exon 14 NSCLC. News release. HUTCHMED. January 13, 2025. Accessed January 14, 2025. https://www.hutch-med.com/nmpa-full-approval-for-orpathys-savolitinib-for-met14-nsclc/
2. HUTCHMED announces savolitinib sNDA accepted in China for treatment-naïve or previously treated patients with locally advanced or metastatic MET exon 14 NSCLC. News release. HUTCHMED. March 28, 2024. Accessed January 14, 2025. https://www.hutch-med.com/savolitinib-china-snda-accepted-ex14-nsclc/
3. 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 14, 2025. https://www.hutch-med.com/orpathys-tagrisso-nda-acceptance-in-china-with-priority-review-status-for-lung-cancer-after-egfri/