Top KOLs Discussing SAVANNAH
SAVANNAH Key Slides & Visuals
SAVANNAH Top Tweets
𝕏Personalised approach at osimertinib PD with savolitinib and osimertinib in MET deregulated EGFRm NSCLC looks promising. Is it better than CT+Ami or ADC? Hwr, it is a chemofree strategy and other treatments could be applied later #ELCC25 https://t.co/PM8MSBFsFB
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
𝕏☑️#WCLC25 #LCSM Mini Oral Abstract🆙 🔥SAVANNAH: Biomarker Concordance and Acquired Resistance in Patients with EGFRm MET-OverExp and / or Amp NSCLC 🎙️ Dr. Christina Baik @OncoAlert @Larvol @IASLC https://t.co/H2B64oYkKO https://t.co/LPmYvWjsUf
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🆕 #ASCO25 🆙 ☑️#LCSM Rapid Oral, Mets 🔥SAVANNAH CNS: savolitinib + osimertinib combination with savo + placebo 🎙️ @benlevylungdoc 🎯Savo + Osi / PBO: ORR 58%/16%, DOR 11.8/4.5m, PFS 8.3/3.6m @OncoAlert @ASCO @Larvol https://t.co/8TzXZqWsNM https://t.co/RXWUYBsdbD https://t.co/7QdidGPUqK
𝕏5. #SAVANNAH: Ph2, n=80, PD on Osimertinib and now w/ MET+ (IHC3+ or Fish+): Osi + Savolitinib. - ORR: 56% and mDoR: 7.1mos - mPFS: 7.4mos - Gr ≥ 3 AEs: 57% - W/ Ami (+Laz) in 1L, resistance mechanism looks different. 6/8 https://t.co/5GQZfFFrR6 https://t.co/xSfkZTq37t
𝕏Dr. @benlevylungdoc presents phase 2 SAVANNAH - randomized subset of savolitinib with osimertinib/placebo in #EGFR NSCLC, MET+ (IHC/FISH) with PD after 1L osimertinib. RR 58% with combo vs 16% with savo alone. In this setting, need to continue EGFR TKI. https://t.co/K7dE5PUsS3
𝕏SAVANNAH: Savolitinib + Osi in 2L MET altered EGFRmut ❓Is Osi needed as well as Savo 👉 Yes. ORR & PFS worse w/o Osi ❓ Is Osi needed for CNS control 👉 Yes. ⬆️ icRR + ⬇️ CNS mets 🤔 Need both Savo+Osi 🤔 Reassuring CNS activity 🤔 Need Ph3 SAFFRON & license #LCSM #ASCO25 https://t.co/qGcR9FVGMv
𝕏#ASCO25 @ASCO #NSCLC #LCSM SAVANNAH (Abstract 8513): Phase 2 randomized study of savolitinib + osimertinib vs savolitinib + placebo in EGFRm advanced NSCLC with MET overexpression/amplification post 1L osimertinib: • 🎯 ORR, DoR, and PFS numerically higher with combo • 🧠 https://t.co/bc38lwft1H
𝕏Now Prof Ahn is presenting the SAVANNAH study at #ELCC25 @myESMO #Esmoambassadors https://t.co/cXsjz7FS0U
About the SAVANNAH Trial
MET pathway activation is the most common targetable mechanism of acquired resistance to osimertinib in EGFR-mutated NSCLC. SAVANNAH asked whether adding savolitinib — an oral, highly selective MET TKI jointly developed by HUTCHMED and AstraZeneca — to continued osimertinib could re-induce responses after progression, and, critically, in whom: the study’s biomarker analyses showed the benefit concentrates in tumors with high-level MET aberration (IHC 3+ in ≥90% of cells and/or FISH ≥10 copies).
Final results at ELCC 2025 (data cut-off Aug 23, 2024) showed durable responses in the primary efficacy population, and physicians on this page immediately benchmarked them against MARIPOSA-2’s amivantamab-chemotherapy arm in the same post-osimertinib space. SAVANNAH’s cut-off became the entry criterion for the global Phase III SAFFRON trial — whose positive PFS/OS topline (Aug 2026) validated the strategy this Phase II built.
Trial Methodology & Results
Study Design
Phase II, open-label, multi-cohort (protocol v1–6 single-arm dose cohorts; v7 added 2:1 randomization vs savolitinib+placebo with crossover). 367 patients enrolled overall.
Primary Efficacy Population
n=80: progression on first-line osimertinib, MET IHC3+/≥90% and/or FISH10+, treated with savolitinib 300 mg BID + osimertinib 80 mg QD.
Interventions
Savolitinib 300 mg BID (primary population; other cohorts 300 mg QD / 600 mg QD) added to continued osimertinib 80 mg QD — all oral.
Endpoints
Primary: ORR (investigator). Secondary: ORR by BICR, PFS, DoR, OS, safety.
Biomarker
Central MET testing; the IHC90+ / FISH10+ high-MET cut-off defined here was carried into SAFFRON.
Sponsors
AstraZeneca and HUTCHMED (savolitinib jointly developed; commercialized by AstraZeneca).
Tumour response (final, ELCC25 — DCO 23 Aug 2024)
Confirmed ORR 56% (95% CI 45–67) by investigator and 55% (43–66) by BICR; CR 1%, PR 55%/54%; median DoR 7.1 months (5.6–9.6) investigator and 9.9 months (6.0–13.7) BICR; median time to onset of response ~6 weeks.
Durable responses in ~1 of 2 high-MET patients after osimertinib failureSource: ELCC25 tumour-response slide (OCR above)
Progression-free survival (final, ELCC25 — DCO 23 Aug 2024)
Median PFS 7.4 months (95% CI 5.5–7.6; events 65/80, maturity 81%) by investigator and 7.5 months (6.4–11.3; events 49/80, maturity 61%) by BICR; landmark PFS approximately 65% at 6 months and 35% at 12 months (BICR). Values transcribed only where legible on the slide.
Source: ELCC25 PFS slide (OCR above)Clinical Implications
⚠ Investigational in the US. SAVANNAH is hypothesis-defining rather than practice-changing on its own: it identified who benefits (high-MET) and how much, justified Switzerland’s temporary authorization, and powered the design of Phase III SAFFRON — now positive for PFS and OS. KOLs also debated its single-arm limits and cross-trial comparisons with MARIPOSA-2 (amivantamab + chemotherapy).
Source: AstraZeneca press release, Aug 17, 2026SAVANNAH in the News
SAVANNAH FAQ
What is the SAVANNAH trial?
SAVANNAH (NCT03778229) is a Phase II trial of savolitinib (Orpathys) added to osimertinib (Tagrisso) in patients with EGFR-mutated advanced NSCLC whose disease progressed on osimertinib and whose tumors show MET overexpression and/or amplification. It enrolled 367 patients across multiple dose cohorts; the primary efficacy population (n=80) received savolitinib 300 mg twice daily plus osimertinib 80 mg once daily after progression on first-line osimertinib, selected at the high-MET cut-off.
What did SAVANNAH show?
In the final results presented at ELCC 2025 (data cut-off August 23, 2024), the primary efficacy population showed a confirmed objective response rate of 56% by investigator assessment (95% CI 45-67) and 55% by blinded independent central review (95% CI 43-66), median duration of response of 7.1 months (investigator) and 9.9 months (BICR), and median progression-free survival of 7.4 months (investigator) and 7.5 months (BICR).
How were patients selected for MET status in SAVANNAH?
By central testing: MET overexpression by immunohistochemistry (3+ staining in at least 90% of tumor cells, IHC90+) and/or amplification by FISH (10 or more copies, FISH10+). SAVANNAH established this high-MET cut-off, which was then carried forward as the prospective selection strategy in the Phase III SAFFRON trial.
Is the savolitinib plus osimertinib combination approved based on SAVANNAH?
Not in the US - the combination is investigational there. Switzerland granted a temporary authorization in this high-MET post-osimertinib setting based on SAVANNAH. In China the combination is approved for MET-amplified EGFRm NSCLC after EGFR-TKI progression based on the SACHI Phase III trial.
What happened after SAVANNAH?
SAVANNAH set the stage for the global Phase III SAFFRON trial, which on August 17, 2026 reported statistically significant improvements in both progression-free and overall survival versus platinum-based chemotherapy - the confirmatory readout for this all-oral, chemotherapy-sparing strategy.