HUTCHMED and AstraZeneca announced positive results from the SAVANNAH Phase II trial, evaluating the combination of TAGRISSO® (osimertinib) and ORPATHYS® (savolitinib) in patients with epidermal growth factor receptor-mutated (EGFRm) non-small cell lung cancer (NSCLC) whose disease progressed on TAGRISSO® and who have high levels of MET overexpression and/or amplification. The study demonstrated a high, clinically meaningful, and durable objective response rate (ORR) in this patient population.
Addressing MET-Driven Resistance in EGFR-Mutated NSCLC
While EGFR-targeted therapies like osimertinib have significantly improved survival for patients with EGFRm NSCLC, resistance often develops, with MET overexpression or amplification being a common mechanism. Approximately 15-50% of patients who progress on osimertinib treatment present with MET aberration.
The SAVANNAH trial enrolled over 360 patients across more than 80 centers globally. Patients had EGFRm, locally advanced or metastatic NSCLC with MET overexpression and/or amplification who had progressed following treatment with TAGRISSO®. The primary endpoint was ORR, with key secondary endpoints including progression-free survival and duration of response.
Myung-Ju Ahn, MD, PhD, principal investigator in the SAVANNAH Phase II trial, noted, "Osimertinib can provide patients with EGFR-mutated lung cancer unprecedented survival and has transformed the treatment landscape, but patients can develop resistance due to genes like MET – a common resistance biomarker. These results show that adding savolitinib, a selective MET-inhibitor, while continuing osimertinib treatment helped to deliver a meaningful response among patients whose disease progressed, providing a potential new treatment option following standard-of-care osimertinib."
Clinical Significance and Future Directions
The combination of TAGRISSO® plus ORPATHYS® has received Fast Track designation from the US Food and Drug Administration (FDA) in this setting. The global SAFFRON Phase III trial, sponsored by AstraZeneca, is underway to further assess the combination versus platinum-based doublet chemotherapy in patients with EGFRm, MET-overexpressed and/or amplified, locally advanced or metastatic NSCLC following TAGRISSO®.
Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, stated, "These positive SAVANNAH results show the benefit of a targeted treatment approach in EGFR-mutated lung cancer patients who experience MET-driven resistance...[they] reinforce the importance of identifying MET aberration and validate our combination strategy to address resistance while allowing continued TAGRISSO® treatment."
About ORPATHYS
ORPATHYS® (savolitinib) is an oral, potent, and highly selective MET tyrosine kinase inhibitor (TKI) that blocks atypical activation of the MET receptor tyrosine kinase pathway. It is approved in China for the treatment of patients with NSCLC with MET exon 14 skipping alterations who have progressed following prior systemic therapy or are unable to receive chemotherapy.
