Home › Trials › NCT05261399

Combination of savolitinib and osimertinib versus chemotherapy for advanced lung cancer

A Phase III, Randomised, Open-Label Study of Savolitinib in Combination With Osimertinib Versus Platinum-Based Doublet Chemotherapy in Participants With EGFR Mutated, MET-Overexpressed and/or Amplified, Locally Advanced or Metastatic Non-Small Cell Lung Cancer Who Have Progressed on Treatment With Osimertinib (SAFFRON).

Phase 3 Interventional AstraZeneca · NCT05261399

This study is testing if a combination of two targeted drugs, savolitinib and osimertinib, works better than standard chemotherapy for patients with advanced lung cancer who have not responded to previous osimertinib treatment.

Quick facts

PhasePhase 3
Study typeInterventional
Enrollment324 (estimated)
Ages18 Years to 130 Years
SexAll
SponsorAstraZeneca Industry-sponsored
Drugs / interventionsosimertinib, savolitinib, radiation, chemotherapy
Locations285 sites (La Jolla, California and 284 other locations)
Trial IDNCT05261399 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the efficacy and safety of savolitinib combined with osimertinib compared to platinum-based doublet chemotherapy in patients with non-small cell lung cancer (NSCLC) who have progressed on osimertinib treatment. It is a multicenter, Phase III, randomized, open-label study involving approximately 324 participants with specific genetic mutations. Participants will receive treatment until disease progression, unacceptable toxicity, or other discontinuation criteria are met. The study aims to provide insights into a new treatment approach for patients with advanced NSCLC.

Who should consider this trial

Good fit: Ideal candidates are adults with EGFR mutated, MET-overexpressed and/or amplified, locally advanced or metastatic NSCLC who have progressed on osimertinib.

Not a fit: Patients without documented EGFR mutations or those who have not progressed on osimertinib may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could offer a more effective treatment option for patients with advanced NSCLC who have not responded to previous osimertinib therapy.

How similar studies have performed: Other studies have shown promising results with similar targeted therapies in NSCLC, indicating potential for success in this approach.

Eligibility criteria

Show full inclusion / exclusion criteria 
Inclusion Criteria:

* Provision of signed and dated written ICF prior to any mandatory and non-mandatory study-specific procedures, sampling and analyses.
* Participant must be ≥18 years (≥ 19 years of age in South Korea) at the time of signing the informed consent. All genders are permitted.
* Histologically or cytologically confirmed locally advanced or metastatic NSCLC which is not amenable to curative therapy.
* Must have at least one documented sensitising EGFR mutation: exon19 deletion, L858R mutation, and/or T790M.
* Documented radiologic progression on first- or second-line treatment with osimertinib as the most recent anti-cancer therapy.
* Mandatory provision of FFPE tumour tissue.
* MET overexpression and/or amplification in tumour specimen collected following progression on prior osimertinib treatment.
* Measurable disease as defined by RECIST 1.1.
* Adequate haematological, liver, renal and cardiac functions, and coagulation parameters.
* ECOG performance status of 0 or 1.

Exclusion Criteria:

* Predominant squamous NSCLC, and small cell lung cancer.
* Prior or current treatment with a third-generation EGFR-TKI other than Osimertinib.
* Prior or current treatment with savolitinib or another MET inhibitors.
* Spinal cord compression or brain metastases, unless asymptomatic and are stable.
* History or active leptomeningeal carcinomatosis.
* Unresolved toxicities from any prior therapy greater than CTCAE Grade 1 and prior platinum-therapy related Grade 2 neuropathies with the exception of alopecia and haemoglobin ≥ 9.0 g/dL.
* Active/unstable cardiac diseases currently or within the last 6 months, clinically significant ECG abnormalities, and/or factors/medications that may affect QTc intervals.
* History of liver cirrhosis of any origin and clinical stage; or history of other serious liver disease or chronic disease with relevant liver involvement.
* Known serious active infection including, but not limited to, tuberculosis, or HIV, HBV or HCV or gastrointestinal disease.
* Receipt of live attenuated vaccine (including against COVID-19) within 30 days prior to the first dose of study intervention.
* Past medical history of ILD, drug-induced ILD, radiation pneumonitis, which required steroid treatment, or any evidence of clinically active ILD.
* Participants currently receiving medications or herbal supplements known to be strong inducers of cytochrome P450 (CYP)3A4 or strong inhibitors of CYP1A2.

Where this trial is running

La Jolla, California and 284 other locations

+235 more sites — see ClinicalTrials.gov for the full list.

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions CarcinomaNon-Small-Cell LungSavolitinibOsimertinibEGFRAmplifiedMetastaticMET Driven
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.