Top KOLs Discussing SAFFRON
SAFFRON Key Slides & Visuals
SAFFRON Top Tweets
𝕏🚨 Phase 3 SAFFRON met its primary endpoint Savolitinib + osimertinib significantly improved PFS and OS vs. platinum-based chemo in EGFRm NSCLC with MET overexpression/amplification after progression on osimertinib. 🔥 First global P3 trial to show both PFS and OS benefit in this setting! 🔗 https://t.co/PXrv3Ld0VN
𝕏SAVANNAH (Ph 2): Savo + Osi EGFRm-resist NSCLC w/MET overexp (IHC90+) and/or ampl (FISH10+)~1/3 resist pts. ORR 55%, DoR 9.9, PFS 7.5 (BICR). vs MARIPOSA-2 (Ph3 Ami+ChT): ORR 53%, DoR 6.9, PFS 6.3 mo. Ph 3 SAFFRON ongoing #ESMOAmbassadors #ELCC25 @myESMO https://t.co/NejMZNEARv
𝕏1st lineでさえ治療選択が難しくなっているのに2nd line以降はより混沌としてきた🤔 FLAURA2耐性後もMET ampは一定（12%）いることから、FLAURA2→SAFFRONのシークエンスにいけると良さそう. いずれにせよ再生検が非常に重要🔬🧬 https://t.co/n5oHF4Arom
𝕏JUST IN: The SAFFRON trial is + for PFS and OS via @AstraZeneca —NSCLC, EGFR-mutated with MET over expression post EGFR-m progression https://t.co/TbdmI9F7gn https://t.co/qFagvTt3dA
𝕏Confirmation of the value of targeting our #EGFRmut MET+ #NSCLC patients at osimertinib progression while continuing osimertinib... a treatment strategy that also makes sense post-FLAURA2 combination, given the significant proportion of MET pathway activation at progression https://t.co/5Y84epB0EU
𝕏Savolitinib plus osimertinib in pts with EGFRm aNSCLC and MET overexpression and/or amplification following PD on osimertinib. #ELCC25 @myESMO ORR 56%, Median DoR 7.1m, Median PFS 7.4m. Phase 3 Trial vs PBC 👉🏻 SAFFRON… Amendment to include Amivantamab in the control arm? 🤔 https://t.co/o8Vn1Fstxm
𝕏“Positive high-level results from the SAFFRON Phase III trial showed Tagrisso (osimertinib) plus Orpathys(savolitinib) demonstrated a statistically significant and clinically meaningful improvement in both progression-free survival (PFS) and overall survival (OS) versus doublet platinum-based chemotherapy in patients with epidermal growth factor receptor-mutated (EGFRm) non-small cell lung cancer (NSCLC). Patients in the trial had tumours with high levels of MET overexpression or amplification and had progressed on prior treatment with Tagrisso.”
𝕏Looks like the SAFFRON study literally MET its endpoint.. Precision medicine is here to stay post-progression on EGFR TKI therapy! https://t.co/NyPnBJp6dP https://t.co/siejGD70g4
𝕏📣SAFFRON is positive (press-release) Osimertinib + savolitinib improves both PFS and OS vs platinum doublet in EGFR-mutant #NSCLC with high #MET overexpression/amplification after progression on osimertinib https://t.co/IbdhJjuBtp #LCSM #EGFR
𝕏Chemo-free hope for #EGFRm #NSCLC: #Savolitinib + osimertinib yields durable responses (ORR 55%) in MET+ pts after Tagrisso. Phase 2 SAVANNAH sets stage for SAFFRON trial. https://t.co/so9Yw6ZqgY #LungCancer #PrecisionOncology #METAlterations #ELCC25 @stephanieplsaw https://t.co/zHIpk8FmpD
About the SAFFRON Trial
MET overexpression and/or amplification is one of the most common mechanisms of acquired resistance to osimertinib in EGFR-mutated NSCLC. SAFFRON tests whether adding savolitinib — an oral, highly selective MET tyrosine kinase inhibitor jointly developed by HUTCHMED and AstraZeneca — to continued osimertinib can beat the platinum-doublet chemotherapy default in patients whose disease progressed on first- or second-line osimertinib as their most recent therapy.
On August 17, 2026, AstraZeneca and HUTCHMED announced positive high-level results: SAFFRON is the first global Phase III trial to show significant progression-free and overall survival benefits in this setting, reinforcing an all-oral, chemotherapy-sparing sequencing option. The program builds on TATTON and the SAVANNAH Phase II trial (which defined the IHC90+/FISH10+ selection), and on SACHI, the China Phase III that already supported the combination’s approval there. Physicians on this page immediately framed the readout around post-FLAURA2 sequencing and the value of routine MET testing at progression.
Trial Methodology & Results
Study Design
Global, randomized (1:1), open-label, multicenter Phase III; 338 patients across 230 centers in 29 countries; last patient randomized October 31, 2025.
Population
Adults with locally advanced or metastatic EGFRm NSCLC (Ex19del/L858R ± T790M), MET-overexpressed (central IHC: 3+ in ≥90% of tumor cells) and/or amplified (FISH ≥10 copies / NGS), progressed on 1st- or 2nd-line osimertinib as most recent therapy.
Interventions
Savolitinib 300 mg BID + osimertinib 80 mg QD (all-oral) vs pemetrexed 500 mg/m² + cisplatin 75 mg/m² or carboplatin AUC5 q21d ×4, then pemetrexed maintenance.
Endpoints
Primary: PFS by BICR (RECIST 1.1). Secondary: OS, ORR, DoR, DCR, TTR, safety.
Companion Diagnostic
Prospective central MET testing (IHC / FISH / NGS) using the SAVANNAH-derived high-MET cut-off (IHC90+ / FISH10+).
Sponsors
AstraZeneca and HUTCHMED (savolitinib jointly developed; commercialized by AstraZeneca).
Efficacy — topline only
Savolitinib + osimertinib delivered a statistically significant and clinically meaningful improvement in PFS (primary endpoint, BICR) and in OS versus platinum-based doublet chemotherapy. No hazard ratios, medians, or response rates have been disclosed yet; full data will be presented at a forthcoming medical meeting.
First global Phase III with significant PFS + OS benefit in this settingSource: AstraZeneca press release, Aug 17, 2026
Safety
Per the topline announcement, the safety profile of osimertinib plus savolitinib was consistent with the known profiles of each medicine, with no new safety findings. Full quantitative safety data (AE rates, discontinuations) have not yet been disclosed and are expected with the full presentation.
Source: AstraZeneca press release, Aug 17, 2026Clinical Implications
⚠ Investigational in the US: the combination is not FDA-approved for this indication (FDA Fast Track designation). ✅ In China, the combination is approved for MET-amplified EGFRm NSCLC after EGFR-TKI progression based on SACHI. Switzerland has granted the combination a temporary authorization in this high-MET setting based on SAVANNAH. If registered globally on SAFFRON, an all-oral targeted doublet would challenge platinum chemotherapy as the default after osimertinib failure in MET-driven disease — and would sharpen the case for routine MET testing (IHC/FISH/NGS) at progression.
Source: HUTCHMED, China approval (SACHI), Jun 2025SAFFRON in the News
SAFFRON FAQ
What is the SAFFRON trial?
SAFFRON (NCT05261399) is a global, randomized, open-label Phase III trial testing savolitinib (Orpathys) added to osimertinib (Tagrisso) versus platinum-pemetrexed doublet chemotherapy in 338 patients with EGFR-mutated, MET-overexpressed and/or amplified, locally advanced or metastatic NSCLC whose disease progressed on first- or second-line osimertinib. It enrolled across 230 centers in 29 countries.
What did the SAFFRON topline results show?
Per the August 17, 2026 announcements from AstraZeneca and HUTCHMED, savolitinib plus osimertinib demonstrated statistically significant and clinically meaningful improvements in both progression-free survival (the primary endpoint, assessed by blinded independent central review) and overall survival versus platinum-based chemotherapy. Numeric results have not yet been disclosed; the data will be presented at a forthcoming medical meeting.
Is the savolitinib plus osimertinib combination FDA approved?
No. The combination is investigational in the United States and has received FDA Fast Track designation for this setting. It is approved in China (June 2025) for EGFR-mutated non-squamous NSCLC with MET amplification after progression on EGFR-inhibitor therapy, based on the SACHI Phase III trial. Osimertinib (Tagrisso) itself is FDA-approved in EGFR-mutated NSCLC.
How were patients selected for MET status in SAFFRON?
MET status was determined prospectively by a central laboratory: MET overexpression by immunohistochemistry (3+ staining intensity in at least 90% of tumor cells, IHC90+) and/or MET amplification by FISH (10 or more copies, FISH10+) or NGS — the higher-level MET cut-off identified in the SAVANNAH Phase II trial.
Why does SAFFRON matter for EGFR-mutant lung cancer?
MET aberration is one of the most common mechanisms of resistance to osimertinib. SAFFRON is the first global Phase III trial to show significant PFS and OS benefits with an all-oral, chemotherapy-sparing targeted combination in this post-osimertinib, MET-driven setting — KOLs on this page frame it as precision medicine displacing the platinum-doublet default.