China NMPA Accepts NDA for ORPATHYS® and TAGRISSO® Combination in NSCLC with MET Amplification
Key Insights
The China NMPA has accepted and granted priority review to the NDA for ORPATHYS (search)® (savolitinib) and TAGRISSO® (osimertinib) combination.
The combination therapy targets locally advanced or metastatic EGFR (search) mutation-positive NSCLC patients with MET amplification after EGFR inhibitor progression.
The NDA is supported by Phase III SACHI trial data, showing improved progression-free survival compared to platinum-based chemotherapy.
HUTCHMED (China) Limited announced that the China National Medical Products Administration (NMPA) has accepted and granted priority review to the New Drug Application (NDA) for the combination of ORPATHYS (search)® (savolitinib) and TAGRISSO® (osimertinib). This combination is intended for the treatment of patients with locally advanced or metastatic epidermal growth factor receptor (EGFR (search)) mutation-positive non-small cell lung cancer (search) (NSCLC) with MET amplification after disease progression on first-line EGFR inhibitor therapy. The acceptance of the NDA triggers a milestone payment from AstraZeneca to HUTCHMED.
Supporting Clinical Data
The NDA is backed by data from the SACHI trial, a Phase III study. The trial evaluated the efficacy and safety of ORPATHYS (search)® and TAGRISSO® compared to platinum-based doublet-chemotherapy in the specified patient population. The primary endpoint was progression-free survival (PFS) as assessed by investigators. Secondary endpoints included PFS by an independent review committee, overall survival (OS), objective response rate (ORR), duration of response (DoR), disease control rate (DCR), time to response (TTR), and safety. An interim analysis by the Independent Data Monitoring Committee (IDMC) indicated that the study met its primary endpoint of PFS, leading to the conclusion of enrollment. The SACHI trial results will be presented at an upcoming scientific conference.
Addressing EGFR-Inhibitor Resistance
Dr. Michael Shi, Head of R&D and Chief Medical Officer of HUTCHMED, stated, "This marks the first regulatory filing for the ORPATHYS (search)® and TAGRISSO® combination. The combination has demonstrated clear evidence to address MET-driven EGFR (search)-inhibitor resistance and offers a continued path for oral treatment." He further added, "With our biomarker-specific approach, we are hopeful to enhance treatment continuity and quality of life for NSCLC patients navigating this challenging journey. We and our partner AstraZeneca have been exploring this combination globally, through an array of late-stage clinical trials including the TATTON, SAVANNAH, SAFFRON and ORCHARD studies, and we hope to bring this all-oral, chemotherapy-free treatment option to patients with MET-driven lung cancer in the near future."
Breakthrough Therapy Designation
In December 2024, the NMPA granted Breakthrough Therapy designation to the ORPATHYS (search)® and TAGRISSO® combination for this potential indication. This designation is reserved for new treatments that target serious conditions and demonstrate substantial advantages over existing therapies.
NSCLC and MET Aberrations
Lung cancer is the leading cause of cancer death, accounting for approximately one-fifth of all cancer deaths. NSCLC represents 80-85% of all lung cancer cases. A significant proportion of NSCLC patients, particularly in Asia (30-40%), have EGFR (search)-mutated NSCLC. MET aberrations, including overexpression and amplification, are implicated in tumor growth, metastasis, and acquired resistance to EGFR TKIs. Approximately 15-50% of patients progressing post-osimertinib treatment exhibit MET aberrations.
Ongoing Clinical Development
The ORPATHYS (search)® and TAGRISSO® combination has been investigated in multiple clinical trials, including TATTON and SAVANNAH. Encouraging results from these studies led to the initiation of Phase III trials such as SACHI and SANOVO in China, and the global SAFFRON study. This combination aims to provide a chemotherapy-free, biomarker-specific, and orally administered treatment option for lung cancer patients.
About ORPATHYS® and TAGRISSO®
ORPATHYS (search)® (savolitinib) is an oral, potent, and selective MET TKI that has shown clinical activity in advanced solid tumors. It targets atypical activation of the MET receptor tyrosine kinase pathway. TAGRISSO® (osimertinib) is a third-generation, irreversible EGFR (search)-TKI with proven clinical activity in NSCLC, including against central nervous system metastases.