MET is the most common biomarker in patients with EGFR-mutated lung cancer who develop resistance to targeted therapy
Global SAFFRON Phase III trial evaluating this combination is underway
Preliminary results from the SAVANNAH Phase II trial showed that Tagrisso (osimertinib) plus savolitinib demonstrated an objective response rate (ORR) of 49% (95% 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.
The highest ORR was observed in patients with high levels of MET who were not treated with prior chemotherapy (52% [95% CI, 41-63%]). In patients whose tumours did not show high levels of MET, the ORR was 9% (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 6-9 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.
While EGFR-targeted 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.1 Among patients screened for enrolment in SAVANNAH, all of whom experienced disease progression on Tagrisso, 62% had tumours with MET overexpression and/or amplification, and more than one-third (34%) met the defined high MET level cut-off.
Myung-Ju Ahn, MD, PhD, Professor of Hemato-Oncology at the Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea, and Principal Investigator in the SAVANNAH Phase II trial, said: “Acquired resistance to targeted therapy and disease progression are difficult realities for most patients with EGFR-mutated non-small cell lung cancer. These preliminary SAVANNAH results potentially support a novel approach for identifying patients with MET overexpression and/or amplification who are most likely to benefit from a MET-directed therapy, like savolitinib. They also suggest that with the right biomarker testing strategy, MET may be a more prevalent target among resistant patients than previously understood, supporting further investigation of the osimertinib plus savolitinib regimen.”
Cristian Massacesi, Chief Medical Officer and Oncology Chief Development Officer, AstraZeneca, said: “The current standard of care for patients with EGFR-mutated lung cancer who progress on targeted treatment is chemotherapy. The results from SAVANNAH suggest savolitinib added to Tagrisso at the time of disease progression could possibly provide these biomarker-selected patients with a potentially less toxic, more effective treatment option. We look forward to better understanding the potential of the Tagrisso plus savolitinib regimen in this trial and in the SAFFRON Phase III trial.”
Weiguo Su, Chief Executive Officer and Chief Scientific Officer, HUTCHMED, said: “It is encouraging to see the savolitinib and Tagrisso combination regimen progress into a global Phase III study, SAFFRON, with a well-supported patient selection strategy that could benefit more patients than previously recognized. The preliminary results of the SAVANNAH study also affirm the role of molecular testing prior to initiating subsequent treatment for non-small cell lung cancer patients who experience disease progression on an EGFR-targeted therapy. We are aligned in pursuing a selective, patient-centric approach in development efforts for savolitinib in this setting.”