Hutchison China MediTech and AstraZeneca have reported positive preliminary safety and clinical activity results of savolitinib from two Phase Ib/II combination trials for epidermal growth factor receptor (EGFR) mutation-positive (EGFRm) non-small cell lung cancer (NSCLC) with MET-amplification.
Savolitinib is an investigational, potent and highly selective oral inhibitor of mesenchymal epithelial transition factor (c-MET) receptor tyrosine kinase enzyme.
According to the results, combination of 600mg savolitinib with 80mg Tagrisso (osimertinib) or 250mg Iressa (gefitinib) showed preliminary anti-tumour activity.
AstraZeneca Research and Early Development Oncology head Susan Galbraith 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.”
The firms evaluated savolitinib and Tagrisso combination in the Phase Ib/II TATTON trial conducted in 66 subjects suffering from EGFRm advanced NSCLC with MET-amplification.
With confirmed safety and anti-tumour activity, the combination is reported to have demonstrated partial response as per Response Evaluation Criteria in Solid Tumours (RECIST) 1.1 criteria in 33% of subjects who previously received third-generation T790M-directed EGFR inhibitors.
Of the total patients who progressed after previous first or second-generation EGFR inhibitor treatment, 61% with T790M mutation negative had a partial response, while it was 55% in case of T790M positive patients.
The combination of savolitinib and Iressa was assessed in a separate Phase Ib/II trial, which indicated a partial response in 31% of patients, with 52% were T790M negative and 9% were positive.
Discovered by Chi-Med, savolitinib is being co-developed in alliance with AstraZeneca for the treatment of various types of tumours such as kidney, lung and gastric cancers.
Image: A chest X-ray showing a tumor in the lung (marked by arrow). Photo: courtesy of James Heilman, MD.