AstraZeneca and its partner Chi-Med presented preliminary safety and clinical activity of savolitinib when given in combination with either Tagrisso (osimertinib) or Iressa (gefitinib) in two Phase Ib trials conducted in patients with epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer (NSCLC) with MET-amplification who had progressed following 1st-line treatment with an EGFR inhibitor.1,2 In both trials, the addition of savolitinib (600mg, once daily), an investigational selective inhibitor of c-MET (mesenchymal epithelial transition factor) receptor tyrosine kinase, to osimertinib (80mg, once daily) or gefitinib (250mg, once daily) demonstrated preliminary anti-tumour activity. The data were shared in two oral presentations at the International Association for the Study of Lung Cancer 18th World Conference on Lung Cancer (WCLC) in Yokohama, Japan, 15-18 October 2017.
Dr. Myung-Ju Ahn, Department of Haematology & Oncology, Samsung Medical Centre, Seoul, South Korea, said: “Secondary resistance mechanisms often emerge during treatment with mutation-targeted medicines, leading to disease progression. The data presented at WCLC demonstrate the potential of utilising savolitinib in cMET-driven lung cancers to address resistance challenges.”
Susan Galbraith, Head of Oncology, AstraZeneca Research and Early Development, said: “We are committed to developing innovative medicines to overcome the key drivers of cancer mechanisms of resistance and are strategically focused on developing effective combinations. The latest results for savolitinib in combination with osimertinib and gefitinib support our approach in collaboration with Chi-Med."
Preliminary results for savolitinib in combination with osimertinib
Early data on safety and anti-tumour activity for savolitinib (600mg, once daily) plus osimertinib (80mg, once daily) in the Phase Ib TATTON trial in patients with EGFR mutation-positive (EGFRm) advanced NSCLC with MET-amplification were presented. In 66 patients treated with savolitinib plus osimertinib, the most common all-causality adverse events (AEs) of any grade were nausea (44%), vomiting (35%), fatigue (30%), and decreased appetite (30%), and were consistent with the known safety profiles of both therapies.
Preliminary data showed partial response according to RECIST 1.1 criteria in 28% of patients previously treated with third-generation T790M-directed EGFR tyrosine kinase inhibitors (TKIs), including osimertinib(n=25). In patients who had progressed after prior treatment with a first- or second-generation EGFR inhibitor, 53% of T790M-negative patients (n=15) had a partial response, while 57% of T790M-positive patients (n=7) had a partial response.
Preliminary data for savolitinib in combination with gefitinib
Data from a Phase Ib trial assessing savolitinib (600mg, once daily) plus gefitinib (250mg, once daily) in patients in China with EGFRm advanced NSCLC with MET-amplification who progressed following EGFR-TKI therapy were also reported. The most common AEs independent of causality in 51 patients were vomiting (39%), increased ALT (37%), increased AST (35%), nausea (35%), and rash (35%), and were consistent with the known safety profiles of both therapies.
Preliminary results showed that 31% of patients achieved a partial response according to RECIST 1.1 criteria, of which 52% of T790M-negative patients (n=23) and 9% of T790M-positive patients (n=23) had a partial response.
Christian Hogg, Chief Executive Officer of Chi-Med, said: “MET-amplification impacts a meaningful proportion of patients with EGFRm NSCLC who experience disease progression following treatment with a tyrosine kinase inhibitor in the first- or second-line setting. Among patients with this difficult-to-treat resistance mechanism, there is a clear unmet medical need.”
