Preliminary results from the Savannah phase-II trial have showed that Tagrisso (osimertinib) plus savolitinib demonstrated an Objective Response Rate (ORR) of 49 per cent (95 per cent confidence interval [CI], 39-59%) in patients with Epidermal Growth Factor Receptor-mutated (EGFRm) Non-Small Cell Lung Cancer (NSCLC) with high levels of MET overexpression and/or amplification, defined as IHC90+ and/or FISH10+, whose disease progressed on treatment with Tagrisso, a statement from AstraZeneca notified.
It said that the highest ORR was observed in patients with high levels of MET who were not treated with prior chemotherapy (52 per cent [95% CI, 41-63%]). In patients whose tumours did not show high levels of MET, the ORR was nine per cent (95% CI, 4-18%). These results are being shared at the International Association for the Study of Lung Cancer 2022 World Conference on Lung Cancer, taking place from 6th to 9th August in Vienna, Austria.
Savolitinib, marketed in China under the brand name Orpathys, is an oral, potent, and highly selective MET Tyrosine Kinase Inhibitor (TKI) being jointly developed and commercialised by AstraZeneca and Hutchmed, added the statement.
While EGFR-targetted therapy can provide a durable survival benefit to patients with EGFRm NSCLC, most will eventually develop resistance to their treatment, with MET being the most common resistance biomarker. Among patients screened for enrolment in Savannah, all of whom experienced disease progression on Tagrisso, 62 per cent had tumours with MET overexpression and/or amplification, and more than one-third (34 per cent) met the defined high MET level cut-off.
In this analysis, patients’ MET overexpression and/or amplification levels were determined by two tests: immunohistochemistry (IHC), which detects if cancer cells have a particular protein or marker on their surface, and Fluorescence In Situ Hybridisation (FISH), which detects a specific DNA sequence from cancer cells. All patients in this analysis (n=193) had at least IHC50+ and/or FISH5+, and were treated with savolitinib 300mg once daily added to Tagrisso 80mg once daily following disease progression on Tagrisso alone.