AstraZeneca has asked the FDA to approve a two-pill combination for people with EGFR-mutated lung cancer whose tumors keep growing on Tagrisso because of changes involving a protein called MET. HUTCHMED announced the U.S. New Drug Application on Sept. 28 for savolitinib, sold in China as Orpathys, plus Tagrisso (osimertinib). The combination is not approved in the United States.
The filing matters to patients who face a hard turn in their care. Tagrisso is a standard daily pill for EGFR-mutated lung cancer, but tumors often find ways around it. When that happens, the usual next step is chemotherapy.
HUTCHMED's acting chief executive officer and chief financial officer, Johnny Cheng, called the filing "an important step toward potentially bringing ORPATHYS plus TAGRISSO to patients in the US, after its approval in China." The FDA has not announced whether it has accepted the application for review or set a decision date.
MET Changes Behind Tagrisso Resistance
A faulty growth signal drives EGFR-mutated lung cancer, and Tagrisso blocks it. Over time, some tumors switch on a backup route through MET, a separate growth receptor. In a blood-based analysis of the FLAURA trial published in Nature Communications, MET amplification (extra copies of the MET gene) was the most common resistance change detected, found in 17 of 109 patients (16%) whose cancer progressed or who stopped first-line Tagrisso.
Savolitinib blocks MET, so the aim is to shut down both routes at once. Patients in the main trial took Tagrisso 80 mg once daily plus savolitinib 300 mg twice daily.
The application covers patients whose tumors have MET overexpression (high levels of MET protein) or MET amplification after their cancer progressed on an EGFR-targeted drug. Doctors can check for extra MET protein with a tissue stain called immunohistochemistry, or for extra MET gene copies with a test called FISH. Patients in the main trial were selected using high-MET cutoffs identified in an earlier phase 2 study called SAVANNAH, according to HUTCHMED. Because labs do not all use the same thresholds, the specific test and cutoff could matter for who qualifies.
MET changes are not the only reason Tagrisso stops working. Some tumors develop new EGFR mutations, change into a different cell type, or turn on other growth signals, so a MET result is one part of a larger testing picture.
What the SAFFRON Trial Showed So Far
The application rests mainly on SAFFRON, a phase 3 trial of 338 patients at 230 centers in 29 countries across North America, Europe, South America, and Asia. Patients whose cancer had progressed on Tagrisso were randomly assigned to the combination or to platinum-based chemotherapy, OncLive reported.
The companies said in August that the combination met its progression-free and overall survival goals, describing the improvements as statistically significant and clinically meaningful. Progression-free survival measures how long patients live without their cancer growing. The companies have not released the actual figures, so the size of the benefit is not yet known. Full results are scheduled for a presentation at the ESMO 2026 Congress. On safety, HUTCHMED said the combination's profile was consistent with each drug's known effects and that no new safety concerns emerged.
An earlier trial in China offers some sense of scale. In SACHI, which enrolled 211 patients with MET amplification whose cancer had progressed on EGFR-targeted treatment, median progression-free survival was 8.2 months with the combination and 4.5 months with chemotherapy. Severe side effects (grade 3 or higher) occurred in 57% of patients in each group, OncLive reported. Those results supported China's approval of the combination in 2025 for EGFR-mutated, MET-amplified lung cancer after EGFR-targeted treatment.
How the Filing Differs From the First-Line SANOVO Trial
MedicalDaily previously reported that adding savolitinib to Tagrisso delayed progression in newly diagnosed patients in a China-only trial called SANOVO. That article noted that SAFFRON, with its global design and overall survival data, was more likely than SANOVO to support a U.S. approval.
The U.S. application targets a different group. SANOVO tested the pills as a first treatment, while the filing covers patients whose cancer has already progressed on an EGFR-targeted drug such as Tagrisso.
The SAFFRON findings released so far come from the companies developing the drugs. Outside experts will be able to judge the results once the full data are presented and published.
What Patients Can Do Now
People whose lung cancer is growing on Tagrisso can ask their oncologist whether a new biopsy or blood test will check for MET and other resistance changes. Test results help determine which treatments and clinical trials may fit. A patient whose earlier testing showed no MET change may still develop one later, since resistance can emerge over time.
Current options after Tagrisso include platinum-based chemotherapy and other FDA-approved regimens, and some patients qualify for clinical trials. Because savolitinib is not sold in the U.S., anyone seeking it now would need a clinical trial or another access pathway. Patients should not stop Tagrisso on their own, since changes to targeted therapy need an oncologist's direction.
U.S. cost and insurance coverage for the combination are not yet known. The next milestones are the full SAFFRON data at ESMO 2026 and word on whether the FDA accepts the filing.
Key Questions Answered
What was filed?
AstraZeneca submitted a U.S. New Drug Application for savolitinib plus Tagrisso in advanced EGFR-mutated lung cancer with MET overexpression or MET amplification after progression on EGFR-targeted treatment.
Is the combination approved in the U.S.?
No. The FDA has not announced whether it accepted the application or when it will decide. The combination is approved in China for patients with MET amplification.
What did the main trial show?
The companies said SAFFRON improved progression-free and overall survival compared with chemotherapy, but they have not released the numbers. Full results are expected at ESMO 2026.
How common is MET-driven resistance?
In a blood-based analysis of the FLAURA trial, MET amplification appeared in 16% of analyzed patients whose cancer progressed on or who stopped first-line Tagrisso.
How is MET tested?
Doctors use a tissue stain for MET protein or a FISH test for extra MET gene copies, usually on a new sample taken after the cancer progresses.
What should patients ask now?
Patients can ask whether their tumor has been retested since progression and whether any clinical trials fit their results.
Published by Medicaldaily.com
