Hutchison China Meditech (HutchMed; NASDAQ: HCM, HKG: 0013) and AstraZeneca (AZ, NASDAQ: AZN) announced the preliminary results of the Phase II SAVANNAH study evaluating the combination of Tagrisso (osimertinib) and Orpathys (savolitinib) in patients with epidermal growth factor receptor – mutated (EGFRm) non-small cell lung cancer (NSCLC) with high levels of MET overexpression and/or amplification, particularly those with disease progression following treatment with Tagrisso.
Study Results
The combination therapy demonstrated an objective response rate (ORR) of 49% (95% confidence interval [CI], 39 – 59%). Notably, the highest ORR of 52% (95% CI, 41 – 63%) was observed in patients with high levels of MET who had not received prior chemotherapy. In contrast, the ORR was 9% (95% CI, 4 – 18%) in patients whose tumors did not show high levels of MET.
Safety Profile
The safety profile of the combination was consistent with the known profiles of the individual treatments, with no new safety signals identified. Grade 3 or higher adverse events (AEs) were experienced by 45% of patients, and AEs related to savolitinib leading to discontinuation occurred in 13% of patients.
Expert Commentary
Dr. Myung – Ju Ahn of Samsung Medical Center in South Korea, the principal investigator of the SAVANNAH study, described the results positively. He stated that they 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.” He also suggested 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.
Ongoing Research
The Tagrisso/savolitinib combination is currently being evaluated in the global Phase III SAFFRON study.
Regulatory Background
Tagrisso, an irreversible third – generation EGFR – TKI with clinical activity against central nervous system metastasis, was approved in China in March 2017 for the treatment of metastatic NSCLC. Orpathys is HutchMed’s third product to reach the market and China’s first mesenchymal – epithelial transformation factor (MET) inhibitor, approved in June 2021 for the treatment of NSCLC with MET exon 14 skipping alterations following chemotherapy. According to the 2011 licensing agreement between HutchMed and AstraZeneca, the first commercial sales will trigger a USD25 million milestone payment, followed by royalty payments of 30%.-Fineline Info & Tech
