*October 2024*
Key Takeaways
- Osimertinib combined with savolitinib shows high response rates in EGFR-mutant, MET-overexpressed/amplified NSCLC patients post-osimertinib progression.
- The SAVANNAH trial confirms the safety profile of the osimertinib and savolitinib combination, with no new safety signals reported
- Fast track designation by the FDA underscores the potential of this combination as a novel treatment option for MET-driven resistance.
- The SAFFRON trial will compare osimertinib plus savolitinib against platinum-based chemotherapy, using the high MET cutoff for patient selection.
Treatment with osimertinib (Tagrisso) in combination with savolitinib (Orpathys) generated a high, durable overall response rate (ORR) in patients with EGFR-mutant, MET-overexpressed and/or -amplified non–small cell lung cancer (NSCLC) who experienced disease progression on osimertinib, according to updated data from the phase 2 SAVANNAH trial (NCT03778229).1
In an announcement from HUTCHMED, the company noted that the combination’s safety profile in SAVANNAH was consistent with the known profiles of both the combination and each individual agent. No new safety signals were reported.
HUTCHMED said detailed results will be presented at an upcoming medical meeting and submitted to global regulatory bodies for review.
“Osimertinib can provide patients with EGFR-mutated lung cancer unprecedented survival and has transformed the treatment landscape, but patients can develop resistance due to genes like MET—a common resistance biomarker,” Myung-Ju Ahn, MD, PhD, principal investigator of the SAVANNAH trial, stated in a news release. “These results show that adding savolitinib, a selective MET inhibitor, while continuing osimertinib treatment, helped to deliver a meaningful response among patients whose disease progressed, providing a potential new treatment option following standard-of-care osimertinib.” Ahn also serves as a professor of hemato-oncology at the Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine in Seoul, South Korea.
Notably, the FDA granted fast track designation to osimertinib plus savolitinib for this indication in 2023.
“These positive SAVANNAH results show the benefit of a targeted treatment approach in [patients with] EGFR-mutated lung cancer who experience MET-driven resistance,” Susan Galbraith, executive vice president of Oncology Research & Development at AstraZeneca, added in the news release. “The improved response rates from [savolitinib] added to [osimertinib], which is the backbone EGFR-mutated lung cancer therapy, reinforce the importance of identifying MET aberration and validate our combination strategy to address resistance while allowing continued [osimertinib] treatment.”
Overview of SAVANNAH
The ongoing global, randomized trial is evaluating the efficacy of adding savolitinib to osimertinib in patients with EGFR-mutant, locally advanced or metastatic NSCLC with MET overexpression and/or amplification, defined as immunohistochemistry 90+ and/or fluorescent in situ hybridization 10+, who experienced disease progression after first- or second-line treatment with osimertinib.
In accordance with the original single-arm trial design, patients received 80 mg of oral osimertinib per day alongside savolitinib at either a once-daily 300 or 600 mg-dose or a twice-daily 300-mg dose. Notably, a registrational component was added to the trial in 2022 comparing the 300 mg of savolitinib twice daily plus osimertinib vs savolitinib plus placebo.
The study’s primary end point is ORR. Key secondary end points consist of progression-free survival and duration of response.
Over 360 patients have been enrolled onto the trial across more than 80 centers globally, including locations in North America, Europe, South America, and Asia. Read more.
