CarcinomaPhase 3SAFFRONNCT05261399
Savolitinib Plus Osimertinib Versus Platinum-based Doublet Chemotherapy in Participants With Non-Small Cell Lung Cancer Who Have Progressed on Osimertinib Treatment
A Phase 3 study testing Savolitinib, Osimertinib and Pemetrexed in people with Carcinoma and Non-Small-Cell Lung, run by AstraZeneca at 214 sites in 27 countries.
Trial summary
Clinical study to investigate the efficacy and safety 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 NSCLC who have progressed on treatment with Osimertinib. Read more about this study
- Who is it for?
- Ages 18 to 130 years
- Conditions the study is for
- Carcinoma, Non-Small-Cell Lung
- What is being tested?
- Savolitinib, Osimertinib and Pemetrexed
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 341 participants
- Where
- 214 sitesin 27 countries
- Study dates
- 3 Aug 2022to 23 Nov 2026
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 130 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
214 sites in 27 countries.
214 sites in 27 countries
China28 sites
Research Site
Baoding, 71030
Research Site
Beijing, 100036
Research Site
Beijing, 101149
Research Site
Bengbu, 233004
Research Site
Changchun, 130012
Research Site
Changsha, 410011
Research Site
Changsha, 41003
Research Site
Chengdu, 610041
Research Site
Chongqing, 400016
Research Site
Fuzhou, 350001
Research Site
Fuzhou, 350011
Research Site
Hangzhou, 310022
Research Site
Harbin, 150040
Research Site
Hefei, 230031
Research Site
Jinan, 250022
Research Site
Linyi, 276000
Research Site
Nanchang, 330006
Research Site
Qingdao, 266035
Research Site
Shanghai, 200030
Research Site
Shenyang, 110001
Research Site
Shenzhen, 518020
Research Site
Wuhan, 430022
Research Site
Wuhan, 430079
Research Site
Xi'an, 710061
Research Site
Xi'an, 710100
Research Site
Xiangfan, 441021
Research Site
Yichang, 443003
Research Site
Zhengzhou, 450008
Japan24 sites
Research Site
Bunkyō City, 113-8603
Research Site
Chūōku, 104-0045
Research Site
Fukuoka, 812-8582
Research Site
Hirosaki-shi, 036-8563
Research Site
Hiroshima, 730-8518
Research Site
Iwakuni-shi, 740-8510
Research Site
Kanazawa, 920-8641
Research Site
Kashiwa, 277-8577
Research Site
Kobe, 650-0017
Research Site
Kobe, 650-0046
Research Site
Kumamoto, 860-8556
Research Site
Kurume-shi, 830-0011
Research Site
Nagasaki, 852-8501
Research Site
Okayama, 700-8558
Research Site
Osaka, 534-0021
Research Site
Osakasayama-shi, 589-8511
Research Site
Sakaishi, 591-8555
Research Site
Sapporo, 003-0804
Research Site
Sapporo, 060-8638
Research Site
Sendai, 980-0873
Research Site
Sunto-gun, 411-8777
Research Site
Utsunomiya, 320-0834
Research Site
Wakayama, 641-8510
Research Site
Yokohama, 241-8515
Italy17 sites
Research Site
Avellino, 83100
Research Site
Aviano, 33081
Research Site
Catania, 95123
Research Site
Meldola, 47014
Research Site
Milan, 20133
Research Site
Milan, 20141
Research Site
Modena, 41124
Research Site
Monserrato, 09042
Research Site
Naples, 80138
Research Site
Orbassano, 10043
Research Site
Padova, 35128
Research Site
Parma, 43126
Research Site
Perugia, 6124
Research Site
Peschiera del Garda, 37019
Research Site
Roma, 00144
Research Site
Roma, 00152
Research Site
Treviso, 31100
Spain15 sites
Research Site
Badajoz, 6006
Research Site
Badalona, 8916
Research Site
Barcelona, 08036
Research Site
Barcelona, 8035
Research Site
Córdoba, 14004
Research Site
Girona, 17007
Research Site
Madrid, 28040
Research Site
Madrid, 28041
Research Site
Majadahonda, 28222
Research Site
Málaga, 29010
Research Site
Pontevedra, 36312
Research Site
Sabadell, 08208
Research Site
Seville, 41009
Research Site
Valencia, 46026
Research Site
Zaragoza, 50009
France13 sites
Research Site
Bobigny, 93000
Research Site
Brest, 29200
Research Site
Créteil, 94010
Research Site
Dijon, 21079
Research Site
Marseille, 13915
Research Site
Paris, 75005
Research Site
Poitiers, 86021
Research Site
Rennes, 35033
Research Site
Rouen, 76000
Research Site
Saint-Herblain, 44800
Research Site
Saint-Quentin, 02321
Research Site
Strasbourg, 67091
Research Site
Suresnes, 92151
Brazil11 sites
Research Site
Belo Horizonte, 30110-022
Research Site
Cachoeiro de Itapemirim, 29308-014
Research Site
Ijuí, 98700-000
Research Site
Porto Alegre, 90035-903
Research Site
Porto Alegre, 90050-170
Research Site
Salvador, 41253-190
Research Site
Salvador, 41950-610
Research Site
São Paulo, 04014-002
Research Site
São Paulo, 04538-132
Research Site
São Paulo, 04556-100
Research Site
Vitória, 29043-260
Germany9 sites
Research Site
Berlin, 14165
Research Site
Chemnitz, 09113
Research Site
Frankfurt A. Main, 60590
Research Site
Gauting, 82131
Research Site
Immenhausen, 34376
Research Site
Löwenstein, 74245
Research Site
München, 81925
Research Site
Münster, 48149
Research Site
Wangen, 88239
South Korea9 sites
Research Site
Goyang-si, 10408
Research Site
Gyeonggi-do, 13620
Research Site
Jinju, 660-702
Research Site
Seoul, 06273
Research Site
Seoul, 06351
Research Site
Seoul, 08308
Research Site
Seoul, 138-736
Research Site
Seoul, 6591
Research Site
Suwon, 16247
Taiwan9 sites
Research Site
Chiayi City, 62247
Research Site
Hsinchu, 300
Research Site
Kaohsiung City, 83301
Research Site
Liuying, 736
Research Site
Taichung, 404
Research Site
Taichung, 40705
Research Site
Taipei, 100
Research Site
Taipei, 11259
Research Site
Taipei, 112
Argentina8 sites
Research Site
Buenos Aires, C1125ABD
Research Site
CABA, C1019ABS
Research Site
Florida, B1602DQD
Research Site
La Rioja, F5300COE
Research Site
Rosario, 2000
Research Site
Rosario, 2123
Research Site
San Miguel de Tucumán, 4000
Research Site
Viedma, R8500ACE
Greece8 sites
Research Site
Athens, 115 27
Research Site
Athens, 11527
Research Site
Chaïdári, 124 62
Research Site
Heraklion, 71110
Research Site
Larissa, 41110
Research Site
Rio, 265 04
Research Site
Thessaloniki, 546 39
Research Site
Thessaloniki, 54622
Thailand7 sites
Research Site
Bangkok, 10210
Research Site
Bangkok, 10700
Research Site
Chanthaburi, 22000
Research Site
Chiang Mai, 50200
Research Site
Dusit, 10300
Research Site
Hat Yai, 90110
Research Site
Muang, 40002
Israel6 sites
Research Site
Afula, 18341
Research Site
Ashdod, 7747629
Research Site
Be’er Ya‘aqov, 70300
Research Site
Hadera, 38100
Research Site
Jerusalem, 91031
Research Site
Tel Aviv, 6423906
Philippines6 sites
Research Site
Bacolod, 6100
Research Site
Davao City, 8000
Research Site
Manila, 1000
Research Site
Quezon City, 1100
Research Site
Quezon City, 1112
Research Site
San Juan City, 1502
Turkey (Türkiye)6 sites
Research Site
Adana, 1370
Research Site
Ankara, 6800
Research Site
Edirne, 22030
Research Site
Istanbul, 34214
Research Site
Istanbul, 34722
Research Site
Izmir, 35100
United States5 sites
Research Site
Honolulu, Hawaii, 96819
Research Site
Nashville, Tennessee, 37232
Research Site
New Brunswick, New Jersey, 08903
Research Site
New York, New York, 10032
Research Site
Orlando, Florida, 32804
Malaysia5 sites
Research Site
Kota Bharu, 15586
Research Site
Kuala Lumpur, 59100
Research Site
Petaling Jaya, 47500
Research Site
Pulau Pinang, 10990
Research Site
Sabak Bernam, 88996
Vietnam5 sites
Research Site
Can Tho, 900000
Research Site
Hanoi, 100000
Research Site
Hanoi, 10000
Research Site
Ho Chi Minh City, 700000
Research Site
Ho Chi Minh City, 70000
Australia4 sites
Research Site
Fremantle, 6160
Research Site
Southport, 4215
Research Site
Waratah NSW, 2298
Research Site
Westmead, 2145
Canada4 sites
Research Site
Montreal, Quebec, H3T 1E2
Research Site
Montreal, Quebec, H3T 1M5
Research Site
Toronto, Ontario, M4N 3M5
Research Site
Toronto, Ontario, M5G 2M9
Belgium3 sites
Research Site
Brussels, 1000
Research Site
Ghent, 9000
Research Site
Roeselare, 8800
United Kingdom3 sites
Research Site
London, SE1 9RT
Research Site
Manchester, M20 4BX
Research Site
Wolverhampton, WV10 0QP
Singapore2 sites
Research Site
Singapore, 169610
Research Site
Singapore, 308433
About this study
Official title: 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).
Clinical study to investigate the efficacy and safety 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 NSCLC who have progressed on treatment with Osimertinib.
Read the detailed description
This is a multicentre, Phase III, randomised, open-label study to investigate the efficacy and safety of savolitinib administered orally in combination with osimertinib versus platinum-based doublet chemotherapy in participants with EGFR mutated, MET-overexpressed and/or amplified, locally advanced or metastatic NSCLC who have progressed on first- or second-line treatment with osimertinib as the most recent therapy.
Approximately 324 participants with EGFR mutated, MET-overexpressed and/or amplified, locally advanced or metastatic NSCLC will be randomly assigned to study intervention with 1:1 ratio.
Patients will be treated until either objective progression of disease (PD) by Response Evaluation Criteria in Solid Tumours 1.1 (RECIST 1.1) is assessed by the investigator, unacceptable toxicity occurs, consent is withdrawn, or another discontinuation criterion is met.
- Conditions
- Carcinoma, Non-Small-Cell Lung
- Being tested
- Savolitinib, Osimertinib, Pemetrexed, Cisplatin, Carboplatin
- Keywords
- Savolitinib, Osimertinib, EGFR, Amplified, Metastatic, MET Driven, carcinoma, NSCLC, overexpressed
- Medical subject headings
- Carcinoma, Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SavolitinibDrug
Also called AZD6094, HMPL-504, volitinib
300 mg savolitinib (3 × 100 mg tablets twice daily) Administrative route : oral
OsimertinibDrug
Also called AZD9291, Tagrisso
80 mg osimertinib
(1 × 80 mg tablet once daily) Administrative route : oral
PemetrexedDrug
Also called NAP
Pemetrexed (500 mg/m2) Administrative route : IV infusion
CisplatinDrug
Also called NAP
Cisplatin (75 mg/m2) Administrative route : IV infusion
CarboplatinDrug
Also called NAP
Carboplatin (AUC5) Administrative route : IV infusion
| Study group | Role | What they receive |
|---|---|---|
| Chemotherapy | Active comparator | Pemetrexed (500 mg/m2) with either cisplatin (75 mg/m2) or carboplatin (AUC5) on Day 1 of 21-day cycles (Q3W) for 4 cycles, followed by pemetrexed maintenance (500 mg/m2) Q3W Receives: Drug: Pemetrexed; Drug: Cisplatin; Drug: Carboplatin |
| Savolitinib + Osimertinib | Experimental | 300 mg savolitinib BID plus 80 mg osimertinib QD Receives: Drug: Savolitinib; Drug: Osimertinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression-free survival (PFS) / savolitinib + osimertinib versus platinum doublet chemotherapy in participants with EGFR mutated, MET-overexpressed and/or amplified, locally advanced or metastatic NSCLC who have progressed on osimertinib.
Defined as time from randomisation until progression per RECIST 1.1 as assessed by BICR, or death due to any cause.
Measured: Approximately 36.5 months post first subject randomized
Secondary outcomes (13)
Overall Survival (OS) /savolitinib + osimertinib versus platinum doublet chemotherapy in participants with EGFR mutated, MET-overexpressed and/or amplified locally advanced or metastatic NSCLC who have progressed on treatment with osimertinib.
Defined as time from randomisation until the date of death due to any cause.
Measured: Approximately 36.5+18 months post first subject randomized.
Progression-free survival (PFS) / savolitinib + osimertinib versus platinum doublet chemotherapy in participants with EGFR mutated, MET-overexpressed, locally advanced or metastatic NSCLC who have progressed on treatment with osimertinib.
Defined as time from randomisation until progression per RECIST 1.1 as assessed by BICR, or death due to any cause.
Measured: Approximately 55 months post first subject randomized
Overall Survival (OS) / savolitinib in combination with osimertinib versus platinum doublet chemotherapy in participants with EGFR mutated, MET-overexpressed by IHC, locally advanced or metastatic NSCLC who have progressed on treatment with osimertinib.
Defined as time from randomisation until the date of death due to any cause.
Measured: Approximately 55 months post first subject randomized
Objective response rate (ORR) savolitinib + osimertinib versus platinum doublet chemotherapy in participants with EGFR mutated, MET-overexpressed and/or amplified locally advanced or metastatic NSCLC who have progressed on treatment with osimertinib.
ORR defined as the proportion of participants who have BOR of a CR or PR, as determined by BICR per RECIST 1.1.
Measured: Approximately 55 months post first subject randomized
Savolitinib+osimertinib vs platinum doublet chemotherapy in terms of BICR-assessed CNS endpoints in participants with EGFR mutated, MET overexpressed and/or amplified, locally advanced or metastatic NSCLC progressed on treatment with osimertinib
CNS PFS, defined as the time from randomisation until the date of CNS progression assessed per CNS modified RECIST v1.1 by BICR or death.
Measured: Approximately 55 months post first subject randomized
Savolitinib+osimertinib vs platinum doublet chemotherapy in terms of BICR-assessed CNS endpoints in participants with EGFR mutated, MET overexpressed and/or amplified, locally advanced or metastatic NSCLC progressed on treatment with osimertinib
CNS ORR defined as the proportion of participants who have a BOR in the CNS by BICR assessment.
Measured: Approximately 55 months post first subject randomized
Savolitinib+osimertinib vs platinum doublet chemotherapy in terms of BICR-assessed CNS endpoints in participants with EGFR mutated, MET overexpressed and/or amplified, locally advanced or metastatic NSCLC progressed on treatment with osimertinib
CNS DoR defined as the time from the date of first documented response in the CNS until the date of objective CNS progression as assessed by BICR or death in the absence of disease progression.
Measured: Approximately 55 months post first subject randomized
Participant-reported pulmonary core symptoms / savolitinib + osimertinib versus platinum doublet chemotherapy in participants with EGFR mutated, MET-overexpressed and/or amplified, locally advanced or metastatic NSCLC who have progressed on osimertinib.
TTD in pulmonary core symptoms (dyspnoea, cough, and chest pain) as measured by the NSCLC-SAQ.
TTD is defined as the time from randomisation until the date of deterioration.
Measured: Approximately 55 months post first subject randomized
Pharmacokinetics (PK) of savolitinib.
Plasma concentrations of savolitinib and its metabolites.
Measured: Approximately 36.5 months post first subject randomized
Disease control rate (DCR) / savolitinib + osimertinib versus platinum doublet chemotherapy in participants with EGFR mutated, MET-overexpressed and/or amplified locally advanced or metastatic NSCLC who have progressed on treatment with osimertinib.
DCR defined as the proportion of participants who have BOR of a CR, PR, or stable disease, as determined by BICR per RECIST 1.1.
Measured: Approximately 55 months post first subject randomized
Time to discontinuation of treatment (TDT) or death / savolitinib + osimertinib vs platinum doublet chemotherapy in participants with EGFR mutated, MET-overexpressed and/or amplified locally advanced or metastatic NSCLC who have progressed on osimertinib
TDT or death is defined as the time from date of randomisation to the earlier of the date of study intervention discontinuation or death.
Measured: Approximately 55 months post first subject randomized
Tumor shrinkage / savolitinib + osimertinib versus platinum doublet chemotherapy in participants with EGFR mutated, MET-overexpressed and/or amplified locally advanced or metastatic NSCLC who have progressed on treatment with osimertinib.
Tumour shrinkage defined as percentage change in tumour size in accordance with RECIST 1.1.
Measured: Approximately 55 months post first subject randomized
Duration of response (DoR) / savolitinib + osimertinib versus platinum doublet chemotherapy in participants with EGFR mutated, MET-overexpressed and/or amplified locally advanced or metastatic NSCLC who have progressed on treatment with osimertinib.
DoR defined as the time from the date of first documented response until date of documented progression per RECIST 1.1 as assessed by BICR, or death in the absence of disease progression.
Measured: Approximately 55 months post first subject randomized
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Mar 2022
- Study start3 Aug 2022
- Primary completion6 Jul 2026
- Study completion23 Nov 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for CarcinomaStudies of the same condition, open and under way.
- More trials run by AstraZenecaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Parallel Assignment
- Masking
- None (open label)
- Enrolment
- 341 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Shun Lu, Prof,MD,PhD,, Principal investigator, Shanghai Chest Hospital, Shanghai JiaoTong University, #241 Huai Hai Road (west), Shanghai, China.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05261399
- Sponsor's protocol ID
- D5087C00001
- Other IDs
- 2024-511169-12-00, 2021-006374-24
- Acronym
- SAFFRON
- Status last verified
- Jul 2026
- First submitted
- 15 Feb 2022
- Last updated
- 6 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.
Publications
Lu S, Girard N, Yang JC, Shepherd FA, Dong X, Arulananda S, Metro G, Hayashi H, Bonanno L, Kim YJ, Liu Z, Ahn MJ, Sun Y, Le TV, Novello S, Kim SW, Zhao Y, Nguyen P, Brandao M, Wang Y, Haigentz M, Misch D, Provencio Pulla M, Huang WT, Baldotto C, Tatangelo M, Lindsay CR, Hartmaier RJ, Lolo R, Swaminathan B, Gont A, Esposito FM, Okuma Y; SAFFRON Investigators. Osimertinib-Savolitinib in Advanced NSCLC after Progression during EGFR-TKI Therapy. N Engl J Med. 2026 Oct 25. doi: 10.1056/NEJMoa2611335. Online ahead of print.
PubMed 42929693
Study at a glance
From the registry record, last updated by the sponsor on 6 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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).
- ClinicalTrials.gov ID
- NCT05261399
- Acronym / sponsor ID
- SAFFRON / D5087C00001
- Conditions
- Carcinoma, Non-Small-Cell Lung
- Keywords
- Savolitinib, Osimertinib, EGFR, Amplified, Metastatic, MET Driven, carcinoma, NSCLC
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 341 participants (actual)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Study start
- 3 Aug 2022 (actual)
- Primary completion
- 6 Jul 2026 (actual)
- Study completion
- 23 Nov 2026 (estimated)
- First posted
- 2 Mar 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Clinical study to investigate the efficacy and safety 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 NSCLC who have progressed on treatment with Osimertinib.
Detailed description
This is a multicentre, Phase III, randomised, open-label study to investigate the efficacy and safety of savolitinib administered orally in combination with osimertinib versus platinum-based doublet chemotherapy in participants with EGFR mutated, MET-overexpressed and/or amplified, locally advanced or metastatic NSCLC who have progressed on first- or second-line treatment with osimertinib as the most recent therapy.
Approximately 324 participants with EGFR mutated, MET-overexpressed and/or amplified, locally advanced or metastatic NSCLC will be randomly assigned to study intervention with 1:1 ratio.
Patients will be treated until either objective progression of disease (PD) by Response Evaluation Criteria in Solid Tumours 1.1 (RECIST 1.1) is assessed by the investigator, unacceptable toxicity occurs, consent is withdrawn, or another discontinuation criterion is met.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Parallel Assignment
| Arm | Type | Receives |
|---|---|---|
| Chemotherapy | Active comparator | Drug: Pemetrexed, Drug: Cisplatin, Drug: CarboplatinPemetrexed (500 mg/m2) with either cisplatin (75 mg/m2) or carboplatin (AUC5) on Day 1 of 21-day cycles (Q3W) for 4 cycles, followed by pemetrexed maintenance (500 mg/m2) Q3W |
| Savolitinib + Osimertinib | Experimental | Drug: Savolitinib, Drug: Osimertinib300 mg savolitinib BID plus 80 mg osimertinib QD |
Who may qualify
- Ages
- 18 to 130 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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.
Key exclusion criteria (12 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SavolitinibAlso: AZD6094, HMPL-504, volitinib300 mg savolitinib (3 × 100 mg tablets twice daily) Administrative route : oral | Drug | Savolitinib + Osimertinib |
| OsimertinibAlso: AZD9291, Tagrisso80 mg osimertinib (1 × 80 mg tablet once daily) Administrative route : oral | Drug | Savolitinib + Osimertinib |
| PemetrexedAlso: NAPPemetrexed (500 mg/m2) Administrative route : IV infusion | Drug | Chemotherapy |
| CisplatinAlso: NAPCisplatin (75 mg/m2) Administrative route : IV infusion | Drug | Chemotherapy |
| CarboplatinAlso: NAPCarboplatin (AUC5) Administrative route : IV infusion | Drug | Chemotherapy |
Primary outcome
Progression-free survival (PFS) / savolitinib + osimertinib versus platinum doublet chemotherapy in participants with EGFR mutated, MET-overexpressed and/or amplified, locally advanced or metastatic NSCLC who have progressed on osimertinib.
Time frame: Approximately 36.5 months post first subject randomized
Defined as time from randomisation until progression per RECIST 1.1 as assessed by BICR, or death due to any cause.
13 secondary outcomes
Overall Survival (OS) /savolitinib + osimertinib versus platinum doublet chemotherapy in participants with EGFR mutated, MET-overexpressed and/or amplified locally advanced or metastatic NSCLC who have progressed on treatment with osimertinib.
Time frame: Approximately 36.5+18 months post first subject randomized.
Progression-free survival (PFS) / savolitinib + osimertinib versus platinum doublet chemotherapy in participants with EGFR mutated, MET-overexpressed, locally advanced or metastatic NSCLC who have progressed on treatment with osimertinib.
Time frame: Approximately 55 months post first subject randomized
Overall Survival (OS) / savolitinib in combination with osimertinib versus platinum doublet chemotherapy in participants with EGFR mutated, MET-overexpressed by IHC, locally advanced or metastatic NSCLC who have progressed on treatment with osimertinib.
Time frame: Approximately 55 months post first subject randomized
Objective response rate (ORR) savolitinib + osimertinib versus platinum doublet chemotherapy in participants with EGFR mutated, MET-overexpressed and/or amplified locally advanced or metastatic NSCLC who have progressed on treatment with osimertinib.
Time frame: Approximately 55 months post first subject randomized
Savolitinib+osimertinib vs platinum doublet chemotherapy in terms of BICR-assessed CNS endpoints in participants with EGFR mutated, MET overexpressed and/or amplified, locally advanced or metastatic NSCLC progressed on treatment with osimertinib
Time frame: Approximately 55 months post first subject randomized
Savolitinib+osimertinib vs platinum doublet chemotherapy in terms of BICR-assessed CNS endpoints in participants with EGFR mutated, MET overexpressed and/or amplified, locally advanced or metastatic NSCLC progressed on treatment with osimertinib
Time frame: Approximately 55 months post first subject randomized
Savolitinib+osimertinib vs platinum doublet chemotherapy in terms of BICR-assessed CNS endpoints in participants with EGFR mutated, MET overexpressed and/or amplified, locally advanced or metastatic NSCLC progressed on treatment with osimertinib
Time frame: Approximately 55 months post first subject randomized
Participant-reported pulmonary core symptoms / savolitinib + osimertinib versus platinum doublet chemotherapy in participants with EGFR mutated, MET-overexpressed and/or amplified, locally advanced or metastatic NSCLC who have progressed on osimertinib.
Time frame: Approximately 55 months post first subject randomized
Pharmacokinetics (PK) of savolitinib.
Time frame: Approximately 36.5 months post first subject randomized
Disease control rate (DCR) / savolitinib + osimertinib versus platinum doublet chemotherapy in participants with EGFR mutated, MET-overexpressed and/or amplified locally advanced or metastatic NSCLC who have progressed on treatment with osimertinib.
Time frame: Approximately 55 months post first subject randomized
Time to discontinuation of treatment (TDT) or death / savolitinib + osimertinib vs platinum doublet chemotherapy in participants with EGFR mutated, MET-overexpressed and/or amplified locally advanced or metastatic NSCLC who have progressed on osimertinib
Time frame: Approximately 55 months post first subject randomized
Tumor shrinkage / savolitinib + osimertinib versus platinum doublet chemotherapy in participants with EGFR mutated, MET-overexpressed and/or amplified locally advanced or metastatic NSCLC who have progressed on treatment with osimertinib.
Time frame: Approximately 55 months post first subject randomized
Duration of response (DoR) / savolitinib + osimertinib versus platinum doublet chemotherapy in participants with EGFR mutated, MET-overexpressed and/or amplified locally advanced or metastatic NSCLC who have progressed on treatment with osimertinib.
Time frame: Approximately 55 months post first subject randomized
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Aug 2026.
- Derived from this study: PubMed 42929693Lu S, Girard N, Yang JC, Shepherd FA, Dong X, Arulananda S, Metro G, Hayashi H, Bonanno L, Kim YJ, Liu Z, Ahn MJ, Sun Y, Le TV, Novello S, Kim SW, Zhao Y, Nguyen P, Brandao M, Wang Y, Haigentz M, Misch D, Provencio Pulla M, Huang WT, Baldotto C, Tatangelo M, Lindsay CR, Hartmaier RJ, Lolo R, Swaminathan B, Gont A, Esposito FM, Okuma Y; SAFFRON Investigators. Osimertinib-Savolitinib in Advanced NSCLC after Progression during EGFR-TKI Therapy. N Engl J Med. 2026 Oct 25. doi: 10.1056/NEJMoa2611335. Online ahead of print.
- Lung Cancer Study Locator details (for US)Link provided by the sponsor.
- Individual participant dataSharing planned: Yes. Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Shun Lu, Prof,MD,PhD, principal investigator
Shanghai Chest Hospital, Shanghai JiaoTong University, #241 Huai Hai Road (west), Shanghai, China.
214 sites in 27 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Savolitinib, Osimertinib and Pemetrexed in people with Carcinoma and Non-Small-Cell Lung, run by AstraZeneca at 214 sites in 27 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 6 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 214 sites in China, Japan, Italy, Spain, France and 22 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression-free survival (PFS) / savolitinib + osimertinib versus platinum doublet chemotherapy in participants with EGFR mutated, MET-overexpressed and/or amplified, locally advanced or metastatic NSCLC who have progressed on osimertinib. (time frame: Approximately 36.5 months post first subject randomized). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05261399, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Aug 2026.