Tagrisso (Osimertinib) is the first-line standard of care for treatment of EGFR-mutant non-small cell lung cancer (NSCLC), however many patients will eventually develop resistance to the drug and experience cancer progression. One of the most common mechanisms of a cancer’s resistance to Tagrisso is MET amplification. Clinical trial results suggest that the addition of the oral highly selective MET TKI Orpathys (savolitinib) to Tagrisso may help overcome this acquired resistance.
About Orpathys (savolitinib)
The c-MET receptor tyrosine kinase is a cancer growth driving mutation that may be present in some individuals with lung, renal and other cancers, and is associated with a poor prognosis. The precision cancer medicine orpathys selectively binds to and inhibits the activation of c-Met and disrupts c-Met signal pathways which prevents cell growth in cancer cells that over express the c-Met protein. Orpathys was recently approved in China for treatment of select patients with NSCLC harboring MET exon 14m and is being evaluated in individuals with several tumor types including lung, kidney, and gastric cancers.1-5
In the currently reported clinical trial results the addition of Orpathys to Tagrisso demonstrated consistent safety and higher anti-cancer activity when compared to treatment with Orpathys alone in patients with EGFR-mutated, MET-amplified advanced NSCLC whose disease had previously progressed on Tagrisso. The combination produced a response rate of 57% compared with 13% for Orpathys alone.
This study was ended early based on the antitumor activity seen in another ongoing phase 2 SAVANNAH study of Orpathys in similar patients.6 The next step for Orpathys to become available in the US is US Food and Drug Administration review and approval which is currently ongoing.
References
1. Chih-Hsin Yang J, Chen YM, Batra U, et al. Savolitinib (savo) + osimertinib (osi) vs savo + placebo (PBO) in patients (pts) with EGFR-mutated (EGFRm), MET-amplified advanced NSCLC with progression on osi. Presented at: 2024 AACR Annual Meeting; April 5-10, 2024; San Diego, CA. Abstract CT251.
2. HUTCHMED receives breakthrough therapy designation in China for savolitinib for gastric cancer. News release. HUTCHMED (China) Limited. August 29, 2023. Accessed August 30, 2023. https://www.hutch-med.com/savolitinib-china-breakthrough-therapy-designation-for-gastric-cancer/
3. Savolitinib for treating gastric cancer and esophagogastric junction adenocarcinoma patients. ClinicalTrials.gov. 2023. https://classic.clinicaltrials.gov/ct2/show/NCT04923932
4. Frigault MM, Markovets A, Nuttall B, et al. Mechanisms of acquired resistance to savolitinib, a selective MET inhibitor in MET-amplified gastric cancer. JCO Precis. 2020;4:222-232. doi:10.1200/PO.19.00386
5. Choueiri TK, Heng DYC, Lee JL, et al. SAVOIR: A phase III study of savolitinib versus sunitinib in pts with MET-driven papillary renal cell carcinoma (PRCC). Presented at: ASCO20 Virtual Scientific Program. J Clin Oncol. 2020;38(suppl):abstr 5002.
