Savolitinib Plus Osimertinib Versus Platinum-based Doublet Chemotherapy in Participants With Non-Small Cell Lung Cancer Who Have Progressed on Osimertinib Treatment
SAFFRON
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).
3 other identifiers
interventional
341
27 countries
214
Brief 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_3
Started Aug 2022
Typical duration for phase_3
214 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
February 15, 2022
CompletedFirst Posted
Study publicly available on registry
March 2, 2022
CompletedStudy Start
First participant enrolled
August 3, 2022
CompletedPrimary Completion
Last participant's last visit for primary outcome
July 6, 2026
CompletedStudy Completion
Last participant's last visit for all outcomes
November 23, 2026
ExpectedAugust 6, 2026
July 1, 2026
3.9 years
February 15, 2022
August 5, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
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.
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.
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.
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.
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.
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
Approximately 55 months post first subject randomized
- +8 more secondary outcomes
Study Arms (2)
Chemotherapy
ACTIVE COMPARATORPemetrexed (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
EXPERIMENTAL300 mg savolitinib BID plus 80 mg osimertinib QD
Interventions
300 mg savolitinib (3 × 100 mg tablets twice daily) Administrative route : oral
80 mg osimertinib (1 × 80 mg tablet once daily) Administrative route : oral
Pemetrexed (500 mg/m2) Administrative route : IV infusion
Eligibility Criteria
You may qualify if:
- 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.
You may not qualify if:
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- AstraZenecalead
Study Sites (214)
Research Site
Orlando, Florida, 32804, United States
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Honolulu, Hawaii, 96819, United States
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New Brunswick, New Jersey, 08903, United States
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New York, New York, 10032, United States
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Nashville, Tennessee, 37232, United States
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Buenos Aires, C1125ABD, Argentina
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CABA, C1019ABS, Argentina
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Florida, B1602DQD, Argentina
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La Rioja, F5300COE, Argentina
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Rosario, 2000, Argentina
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Rosario, 2123, Argentina
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San Miguel de Tucumán, 4000, Argentina
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Viedma, R8500ACE, Argentina
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Fremantle, 6160, Australia
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Southport, 4215, Australia
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Waratah NSW, 2298, Australia
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Westmead, 2145, Australia
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Brussels, 1000, Belgium
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Ghent, 9000, Belgium
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Roeselare, 8800, Belgium
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Belo Horizonte, 30110-022, Brazil
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Cachoeiro de Itapemirim, 29308-014, Brazil
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Ijuí, 98700-000, Brazil
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Porto Alegre, 90035-903, Brazil
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Porto Alegre, 90050-170, Brazil
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Salvador, 41253-190, Brazil
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Salvador, 41950-610, Brazil
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São Paulo, 04014-002, Brazil
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São Paulo, 04538-132, Brazil
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São Paulo, 04556-100, Brazil
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Vitória, 29043-260, Brazil
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Toronto, Ontario, M4N 3M5, Canada
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Toronto, Ontario, M5G 2M9, Canada
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Montreal, Quebec, H3T 1E2, Canada
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Montreal, Quebec, H3T 1M5, Canada
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Santiago, 7500713, Chile
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Baoding, 71030, China
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Beijing, 100036, China
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Beijing, 101149, China
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Bengbu, 233004, China
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Changchun, 130012, China
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Changsha, 410011, China
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Changsha, 41003, China
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Chengdu, 610041, China
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Chongqing, 400016, China
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Fuzhou, 350001, China
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Fuzhou, 350011, China
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Hangzhou, 310022, China
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Harbin, 150040, China
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Hefei, 230031, China
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Jinan, 250022, China
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Linyi, 276000, China
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Nanchang, 330006, China
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Qingdao, 266035, China
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Shanghai, 200030, China
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Shenyang, 110001, China
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Shenzhen, 518020, China
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Wuhan, 430022, China
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Wuhan, 430079, China
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Xi'an, 710061, China
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Xi'an, 710100, China
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Xiangfan, 441021, China
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Yichang, 443003, China
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Zhengzhou, 450008, China
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Bobigny, 93000, France
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Brest, 29200, France
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Créteil, 94010, France
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Dijon, 21079, France
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Marseille, 13915, France
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Paris, 75005, France
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Poitiers, 86021, France
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Rennes, 35033, France
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Rouen, 76000, France
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Saint-Herblain, 44800, France
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Saint-Quentin, 02321, France
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Strasbourg, 67091, France
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Suresnes, 92151, France
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Berlin, 14165, Germany
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Chemnitz, 09113, Germany
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Frankfurt A. Main, 60590, Germany
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Gauting, 82131, Germany
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Immenhausen, 34376, Germany
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Löwenstein, 74245, Germany
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München, 81925, Germany
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Münster, 48149, Germany
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Wangen, 88239, Germany
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Athens, 115 27, Greece
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Athens, 11527, Greece
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Chaïdári, 124 62, Greece
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Heraklion, 71110, Greece
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Larissa, 41110, Greece
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Rio, 265 04, Greece
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Thessaloniki, 546 39, Greece
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Thessaloniki, 54622, Greece
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Hong Kong, 999077, Hong Kong
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Kowloon, Hong Kong
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Afula, 18341, Israel
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Ashdod, 7747629, Israel
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Be’er Ya‘aqov, 70300, Israel
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Hadera, 38100, Israel
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Jerusalem, 91031, Israel
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Tel Aviv, 6423906, Israel
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Avellino, 83100, Italy
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Aviano, 33081, Italy
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Catania, 95123, Italy
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Meldola, 47014, Italy
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Milan, 20133, Italy
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Milan, 20141, Italy
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Modena, 41124, Italy
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Monserrato, 09042, Italy
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Naples, 80138, Italy
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Orbassano, 10043, Italy
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Padova, 35128, Italy
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Parma, 43126, Italy
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Perugia, 6124, Italy
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Peschiera del Garda, 37019, Italy
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Roma, 00144, Italy
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Roma, 00152, Italy
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Treviso, 31100, Italy
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Bunkyō City, 113-8603, Japan
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Chūōku, 104-0045, Japan
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Fukuoka, 812-8582, Japan
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Hirosaki-shi, 036-8563, Japan
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Hiroshima, 730-8518, Japan
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Iwakuni-shi, 740-8510, Japan
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Kanazawa, 920-8641, Japan
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Kashiwa, 277-8577, Japan
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Kobe, 650-0017, Japan
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Kobe, 650-0046, Japan
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Kumamoto, 860-8556, Japan
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Kurume-shi, 830-0011, Japan
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Nagasaki, 852-8501, Japan
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Okayama, 700-8558, Japan
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Osaka, 534-0021, Japan
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Osakasayama-shi, 589-8511, Japan
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Sakaishi, 591-8555, Japan
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Sapporo, 003-0804, Japan
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Sapporo, 060-8638, Japan
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Sendai, 980-0873, Japan
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Sunto-gun, 411-8777, Japan
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Utsunomiya, 320-0834, Japan
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Wakayama, 641-8510, Japan
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Yokohama, 241-8515, Japan
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Kota Bharu, 15586, Malaysia
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Kuala Lumpur, 59100, Malaysia
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Petaling Jaya, 47500, Malaysia
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Pulau Pinang, 10990, Malaysia
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Sabak Bernam, 88996, Malaysia
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Bacolod, 6100, Philippines
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Davao City, 8000, Philippines
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Manila, 1000, Philippines
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Quezon City, 1100, Philippines
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Quezon City, 1112, Philippines
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San Juan City, 1502, Philippines
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Lodz, 93-338, Poland
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Olsztyn, 10-357, Poland
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Singapore, 169610, Singapore
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Singapore, 308433, Singapore
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Goyang-si, 10408, South Korea
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Gyeonggi-do, 13620, South Korea
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Jinju, 660-702, South Korea
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Seoul, 06273, South Korea
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Seoul, 06351, South Korea
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Seoul, 08308, South Korea
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Seoul, 138-736, South Korea
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Seoul, 6591, South Korea
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Suwon, 16247, South Korea
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Badajoz, 6006, Spain
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Badalona, 8916, Spain
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Barcelona, 08036, Spain
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Barcelona, 8035, Spain
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Córdoba, 14004, Spain
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Girona, 17007, Spain
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Madrid, 28040, Spain
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Madrid, 28041, Spain
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Majadahonda, 28222, Spain
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Málaga, 29010, Spain
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Pontevedra, 36312, Spain
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Sabadell, 08208, Spain
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Seville, 41009, Spain
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Valencia, 46026, Spain
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Zaragoza, 50009, Spain
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Baden, CH-5405, Switzerland
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Zurich, 8063, Switzerland
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Chiayi City, 62247, Taiwan
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Hsinchu, 300, Taiwan
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Kaohsiung City, 83301, Taiwan
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Liuying, 736, Taiwan
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Taichung, 404, Taiwan
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Taichung, 40705, Taiwan
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Taipei, 100, Taiwan
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Taipei, 11259, Taiwan
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Taipei, 112, Taiwan
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Bangkok, 10210, Thailand
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Bangkok, 10700, Thailand
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Chanthaburi, 22000, Thailand
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Chiang Mai, 50200, Thailand
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Dusit, 10300, Thailand
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Hat Yai, 90110, Thailand
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Muang, 40002, Thailand
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Adana, 1370, Turkey (Türkiye)
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Ankara, 6800, Turkey (Türkiye)
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Edirne, 22030, Turkey (Türkiye)
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Istanbul, 34214, Turkey (Türkiye)
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Istanbul, 34722, Turkey (Türkiye)
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Izmir, 35100, Turkey (Türkiye)
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London, SE1 9RT, United Kingdom
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Manchester, M20 4BX, United Kingdom
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Wolverhampton, WV10 0QP, United Kingdom
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Can Tho, 900000, Vietnam
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Hanoi, 100000, Vietnam
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Hanoi, 10000, Vietnam
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Ho Chi Minh City, 700000, Vietnam
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Ho Chi Minh City, 70000, Vietnam
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Shun Lu, Prof,MD,PhD,
Shanghai Chest Hospital, Shanghai JiaoTong University, #241 Huai Hai Road (west), Shanghai, China.
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
February 15, 2022
First Posted
March 2, 2022
Study Start
August 3, 2022
Primary Completion
July 6, 2026
Study Completion (Estimated)
November 23, 2026
Last Updated
August 6, 2026
Record last verified: 2026-07
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, CSR
- Time Frame
- AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
- Access Criteria
- When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment Vivli.org. Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.
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.