Savolitinib Plus Osimertinib Versus Platinum-based Doublet Chemotherapy in Participants With Non-Small Cell Lung Cancer Who Have Progressed on Osimertinib Treatment

Carcinoma Clinical Trial

— SAFFRON  

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 Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05261399
• Other study ID #: D5087C00001
• Secondary ID: 2024-511169-12-0
• Status: Recruiting
• Phase: Phase 3
• Start date: August 3, 2022
• Est. completion date: November 30, 2026

Study information

• Verified date: April 2024
• Source: AstraZeneca
• Contact: AstraZeneca Clinical Study Information Center
• Phone: 1-877-240-9479
• Email: information.center[@]astrazeneca.com
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

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Criteria in Solid Tumours 1.1 (RECIST 1.1) is assessed by the investigator, unacceptable toxicity occurs, consent is withdrawn, or another discontinuation criterion is met.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 324
• Est. completion date: November 30, 2026
• Est. primary completion date: May 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 130 Years

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Non-Small-Cell Lung
• Non-Small-Cell Lung

Intervention

Drug:
• Savolitinib
300 mg savolitinib (3 × 100 mg tablets twice daily) Administrative route : oral
• Osimertinib
80 mg osimertinib (1 × 80 mg tablet once daily) Administrative route : oral
• Pemetrexed
Pemetrexed (500 mg/m2) Administrative route : IV infusion
• Cisplatin
Cisplatin (75 mg/m2) or Administrative route : IV infusion
• Carboplatin
Carboplatin (AUC5) Administrative route : IV infusion

Locations

Country	Name	City	State
Argentina	Research Site	Berazategui
Argentina	Research Site	Buenos Aires
Argentina	Research Site	Caba
Argentina	Research Site	Cordoba
Argentina	Research Site	Florida
Argentina	Research Site	La Rioja
Argentina	Research Site	Rosario
Argentina	Research Site	Rosario
Argentina	Research Site	San Miguel de Tucumán
Argentina	Research Site	Viedma
Australia	Research Site	Clayton
Australia	Research Site	Fremantle
Australia	Research Site	Geelong
Australia	Research Site	Liverpool
Australia	Research Site	Waratah NSW
Austria	Research Site	Graz
Austria	Research Site	Salzburg
Austria	Research Site	Wien
Belgium	Research Site	Bruxelles
Belgium	Research Site	Bruxelles
Belgium	Research Site	Edegem
Belgium	Research Site	Gent
Belgium	Research Site	Hasselt
Belgium	Research Site	Mons
Belgium	Research Site	Roeselare
Belgium	Research Site	Sint-Niklaas
Brazil	Research Site	Belo Horizonte
Brazil	Research Site	Brasilia
Brazil	Research Site	Cachoeiro de Itapemirim
Brazil	Research Site	Curitiba
Brazil	Research Site	Ijuí
Brazil	Research Site	Ipatinga
Brazil	Research Site	Porto Alegre
Brazil	Research Site	Porto Alegre
Brazil	Research Site	Porto Alegre
Brazil	Research Site	Rio De Janeiro
Brazil	Research Site	Rio De Janeiro
Brazil	Research Site	Salvador
Brazil	Research Site	Salvador
Brazil	Research Site	São Paulo
Brazil	Research Site	São Paulo
Brazil	Research Site	São Paulo
Brazil	Research Site	Vitória
Bulgaria	Research Site	Haskovo
Bulgaria	Research Site	Pleven
Bulgaria	Research Site	Plovdiv
Bulgaria	Research Site	Sofia
Bulgaria	Research Site	Varna
Bulgaria	Research Site	Vratsa
Canada	Research Site	Mississauga	Ontario
Canada	Research Site	Montreal	Quebec
Canada	Research Site	Montreal	Quebec
Canada	Research Site	Toronto	Ontario
Chile	Research Site	Santiago
Chile	Research Site	Santiago
Chile	Research Site	Temuco
China	Research Site	Baoding
China	Research Site	Beijing
China	Research Site	Beijing
China	Research Site	Bengbu
China	Research Site	Changchun
China	Research Site	Changsha
China	Research Site	Changsha
China	Research Site	Chengdu
China	Research Site	Chongqing
China	Research Site	Fuzhou
China	Research Site	Fuzhou
China	Research Site	Hangzhou
China	Research Site	Hankou,Wuhan
China	Research Site	Harbin
China	Research Site	Hefei
China	Research Site	Jinan
China	Research Site	Linyi
China	Research Site	Nanchang
China	Research Site	Qingdao
China	Research Site	Shanghai
China	Research Site	Shenyang
China	Research Site	Shenzhen
China	Research Site	Wuhan
China	Research Site	Xian
China	Research Site	Xiangfan
China	Research Site	Yichang
China	Research Site	Zhengzhou
France	Research Site	Angers
France	Research Site	Bobigny
France	Research Site	Bordeaux Cedex
France	Research Site	Brest
France	Research Site	Creteil
France	Research Site	Dijon
France	Research Site	Marseille
France	Research Site	Montpellier
France	Research Site	Paris
France	Research Site	Paris
France	Research Site	Poitiers
France	Research Site	Rennes Cedex 9
France	Research Site	Rouen
France	Research Site	Saint-Herblain
France	Research Site	Saint-Quentin cedex
France	Research Site	Strasbourg Cedex
France	Research Site	Suresnes Cedex
Germany	Research Site	Berlin
Germany	Research Site	Berlin
Germany	Research Site	Chemnitz
Germany	Research Site	Frankfurt A. Main
Germany	Research Site	Gauting
Germany	Research Site	Homburg
Germany	Research Site	Immenhausen
Germany	Research Site	Löwenstein
Germany	Research Site	Muenster
Germany	Research Site	München
Germany	Research Site	Stuttgart
Germany	Research Site	Wangen
Greece	Research Site	Athens
Greece	Research Site	Athens
Greece	Research Site	Chaidari
Greece	Research Site	Heraklion
Greece	Research Site	Larissa
Greece	Research Site	Rio
Greece	Research Site	Thessaloniki
Greece	Research Site	Thessaloniki
Hong Kong	Research Site	HKG
Hong Kong	Research Site	Hong Kong
Hong Kong	Research Site	Kowloon
Israel	Research Site	Afula
Israel	Research Site	Ashdod
Israel	Research Site	Be'er Ya'akov
Israel	Research Site	Hadera
Israel	Research Site	Jerusalem
Israel	Research Site	Tel Aviv
Italy	Research Site	Avellino
Italy	Research Site	Aviano
Italy	Research Site	Catania
Italy	Research Site	Meldola
Italy	Research Site	Milan
Italy	Research Site	Milano
Italy	Research Site	Modena
Italy	Research Site	Monserrato
Italy	Research Site	Napoli
Italy	Research Site	Orbassano
Italy	Research Site	Padova
Italy	Research Site	Parma
Italy	Research Site	Perugia
Italy	Research Site	Peschiera Del Garda
Italy	Research Site	Roma
Italy	Research Site	Roma
Italy	Research Site	Treviso
Japan	Research Site	Bunkyo-ku
Japan	Research Site	Chuo-ku
Japan	Research Site	Fukuoka-shi
Japan	Research Site	Hirosaki-shi
Japan	Research Site	Hiroshima-shi
Japan	Research Site	Iwakuni-shi
Japan	Research Site	Kanazawa-shi
Japan	Research Site	Kashiwa
Japan	Research Site	Kobe
Japan	Research Site	Kobe-shi
Japan	Research Site	Kumamoto-shi
Japan	Research Site	Kurume-shi
Japan	Research Site	Matsuyama
Japan	Research Site	Nagasaki-shi
Japan	Research Site	Okayama-shi
Japan	Research Site	Osaka-shi
Japan	Research Site	Osakasayama-shi
Japan	Research Site	Sakai-shi
Japan	Research Site	Sapporo-shi
Japan	Research Site	Sapporo-shi
Japan	Research Site	Sendai-shi
Japan	Research Site	Sunto-gun
Japan	Research Site	Utsunomiya-shi
Japan	Research Site	Wakayama-shi
Japan	Research Site	Yokohama-shi
Korea, Republic of	Research Site	Goyang-si
Korea, Republic of	Research Site	Gyeonggi-do
Korea, Republic of	Research Site	Incheon
Korea, Republic of	Research Site	Jinju-si
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Suwon
Korea, Republic of	Research Site	Ulsan
Malaysia	Research Site	Kota Bharu
Malaysia	Research Site	Pulau Pinang
Malaysia	Research Site	Sabah
Netherlands	Research Site	Amsterdam
Philippines	Research Site	Bacolod
Philippines	Research Site	Baguio City
Philippines	Research Site	Cebu
Philippines	Research Site	Cebu City
Philippines	Research Site	Davao City
Philippines	Research Site	Manila
Philippines	Research Site	Quezon City
Philippines	Research Site	Quezon City
Philippines	Research Site	San Juan
Poland	Research Site	Bialystok
Poland	Research Site	Krakow
Poland	Research Site	Lódz
Poland	Research Site	Olsztyn
Russian Federation	Research Site	Chelyabinsk
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Saint Petersburg
Russian Federation	Research Site	Tomsk
Singapore	Research Site	Singapore
Singapore	Research Site	Singapore
Spain	Research Site	Badajoz
Spain	Research Site	Badalona
Spain	Research Site	Barcelona
Spain	Research Site	Barcelona
Spain	Research Site	Cordoba
Spain	Research Site	Girona
Spain	Research Site	La Coruña
Spain	Research Site	Madrid
Spain	Research Site	Madrid
Spain	Research Site	Madrid
Spain	Research Site	Majadahonda
Spain	Research Site	Málaga
Spain	Research Site	Pontevedra
Spain	Research Site	Sabadell
Spain	Research Site	Sevilla
Spain	Research Site	Valencia
Spain	Research Site	Zaragoza
Switzerland	Research Site	Baden
Switzerland	Research Site	Basel
Switzerland	Research Site	Bern
Switzerland	Research Site	Winterthur
Switzerland	Research Site	Zürich
Taiwan	Research Site	Chiayi
Taiwan	Research Site	Hsinchu
Taiwan	Research Site	Kaohsiung City
Taiwan	Research Site	Liuying
Taiwan	Research Site	Taichung
Taiwan	Research Site	Taichung
Taiwan	Research Site	Taipei
Taiwan	Research Site	Taipei 112
Taiwan	Research Site	Taipei City
Thailand	Research Site	Bangkok
Thailand	Research Site	Chiang Mai
Thailand	Research Site	Dusit
Thailand	Research Site	Hat Yai
Thailand	Research Site	Muang
Thailand	Research Site	Mueang Chanthaburi
Turkey	Research Site	Adana
Turkey	Research Site	Ankara
Turkey	Research Site	Edirne
Turkey	Research Site	Istanbul
Turkey	Research Site	Istanbul
Turkey	Research Site	Izmir
United Kingdom	Research Site	Bristol
United Kingdom	Research Site	Leicester
United Kingdom	Research Site	Liverpool
United Kingdom	Research Site	London
United Kingdom	Research Site	Manchester
United Kingdom	Research Site	Newport
United Kingdom	Research Site	Reading
United Kingdom	Research Site	Wolverhampton
United States	Research Site	Boston	Massachusetts
United States	Research Site	Boston	Massachusetts
United States	Research Site	Canton	Ohio
United States	Research Site	Detroit	Michigan
United States	Research Site	Evergreen Park	Illinois
United States	Research Site	Florham Park	New Jersey
United States	Research Site	Honolulu	Hawaii
United States	Research Site	La Jolla	California
United States	Research Site	Nashville	Tennessee
United States	Research Site	New Brunswick	New Jersey
United States	Research Site	New York	New York
United States	Research Site	Orange City	Florida
United States	Research Site	Orlando	Florida
Vietnam	Research Site	Hanoi
Vietnam	Research Site	Hanoi
Vietnam	Research Site	Hanoi City
Vietnam	Research Site	Ho Chi Minh
Vietnam	Research Site	Ho Chi Minh city

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Countries where clinical trial is conducted

United States,  Vietnam,  Argentina,  Australia,  Austria,  Belgium,  Brazil,  Bulgaria,  Canada,  Chile,  China,  France,  Germany,  Greece,  Hong Kong,  Israel,  Italy,  Japan,  Korea, Republic of,  Malaysia,  Netherlands,  Philippines,  Poland,  Russian Federation,  Singapore,  Spain,  Switzerland,  Taiwan,  Thailand,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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 55 months post first subject randomized
Secondary	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.	Approximately 55 months post first subject randomized.
Secondary	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.	Approximately 55 months post first subject randomized
Secondary	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.	Approximately 55 months post first subject randomized
Secondary	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.	Approximately 55 months post first subject randomized
Secondary	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.	Approximately 55 months post first subject randomized
Secondary	Pharmacokinetics (PK) of savolitinib.	Plasma concentrations of savolitinib and its metabolites.	6 weeks after last patient dosed
Secondary	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.	Approximately 55 months post first subject randomized
Secondary	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.	Approximately 55 months post first subject randomized
Secondary	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.	Approximately 55 months post first subject randomized
Secondary	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.	Approximately 55 months post first subject randomized