Clinical trial NCT05261399: Savolitinib Plus Osimertinib Versus Platinum-based Doublet Chemotherapy in Participants With Non-Small Cell Lung Cancer Who Have Progressed on Osimertinib Treatment
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).
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Carcinoma
Non-Small-Cell Lung
Keywords: Savolitinib
Osimertinib
EGFR
Amplified
Metastatic
MET Driven
carcinoma
NSCLC
overexpressed
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2022-03-02
Enrollment: 324
Sex: ALL
Minimum age (years): 18
Maximum age (years): 130
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Parallel Assignment
Primary purpose: TREATMENT

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.

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Criteria in Solid Tumours 1.1 (RECIST 1.1) is assessed by the investigator, unacceptable toxicity occurs, consent is withdrawn, or another discontinuation criterion is met.

Eligibility 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.

Primary outcomes:
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.
timeFrame: Approximately 55 months post first subject randomized
Secondary outcomes:
measure: 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.
timeFrame: Approximately 55 months post first subject randomized.
measure: 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.
timeFrame: Approximately 55 months post first subject randomized
measure: 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.
timeFrame: Approximately 55 months post first subject randomized
measure: 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.
timeFrame: Approximately 55 months post first subject randomized
measure: 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.
timeFrame: Approximately 55 months post first subject randomized
measure: Pharmacokinetics (PK) of savolitinib.
timeFrame: 6 weeks after last patient dosed
measure: 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.
timeFrame: Approximately 55 months post first subject randomized
measure: 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
timeFrame: Approximately 55 months post first subject randomized
measure: 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.
timeFrame: Approximately 55 months post first subject randomized
measure: 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.
timeFrame: Approximately 55 months post first subject randomized
Other outcomes:
Locations:
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state: Quebec
city: Santiago
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city: Temuco
country: Chile
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city: Baoding
country: China
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city: Beijing
country: China
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country: China
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country: China
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country: China
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country: China
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country: China
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country: China
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country: China
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country: China
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country: China
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country: China
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city: Hangzhou
country: China
facility: Research Site
city: Hankou,Wuhan
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city: Harbin
country: China
facility: Research Site
city: Hefei
country: China
facility: Research Site
city: Jinan
country: China
facility: Research Site
city: Linyi
country: China
facility: Research Site
city: Nanchang
country: China
facility: Research Site
city: Qingdao
country: China
facility: Research Site
city: Shanghai
country: China
facility: Research Site
city: Shenyang
country: China
facility: Research Site
city: Shenzhen
country: China
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city: Wuhan
country: China
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city: Xi'an
country: China
facility: Research Site
city: Xiangfan
country: China
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city: Xian
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city: Yichang
country: China
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city: Zhengzhou
country: China
facility: Research Site
city: Angers
country: France
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city: Bobigny
country: France
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city: Bordeaux Cedex
country: France
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city: Brest
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city: Creteil
country: France
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city: Dijon
country: France
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city: Marseille
country: France
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city: Montpellier
country: France
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city: Paris
country: France
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city: Paris
country: France
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city: Poitiers
country: France
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city: Rennes
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city: Rouen
country: France
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city: Saint-Herblain
country: France
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city: Saint-Quentin
country: France
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city: Strasbourg Cedex
country: France
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city: Suresnes Cedex
country: France
facility: Research Site
city: Berlin
country: Germany
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city: Berlin
country: Germany
facility: Research Site
city: Chemnitz
country: Germany
facility: Research Site
city: Frankfurt A. Main
country: Germany
facility: Research Site
city: Gauting
country: Germany
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city: Homburg
country: Germany
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city: Immenhausen
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city: Löwenstein
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city: Muenster
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city: München
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city: Stuttgart
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city: Wangen
country: Germany
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city: Athens
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city: Chaidari
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city: Heraklion
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city: Larissa
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city: Rio
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city: Thessaloniki
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city: HKG
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city: Napoli
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city: Orbassano
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city: Padova
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city: Fukuoka-shi
country: Japan
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city: Hirosaki-shi
country: Japan
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country: Japan
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city: Iwakuni-shi
country: Japan
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city: Kanazawa-shi
country: Japan
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city: Kashiwa
country: Japan
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city: Kobe-shi
country: Japan
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city: Kobe
country: Japan
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city: Kumamoto-shi
country: Japan
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city: Kurume-shi
country: Japan
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city: Matsuyama
country: Japan
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city: Nagasaki-shi
country: Japan
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city: Okayama-shi
country: Japan
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city: Osaka-shi
country: Japan
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city: Osakasayama-shi
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city: Sakai-shi
country: Japan
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city: Sapporo-shi
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city: Sapporo-shi
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facility: Research Site
city: Sendai-shi
country: Japan
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city: Sunto-gun
country: Japan
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city: Utsunomiya-shi
country: Japan
facility: Research Site
city: Wakayama-shi
country: Japan
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city: Yokohama-shi
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facility: Research Site
city: Goyang-si
country: Korea, Republic of
facility: Research Site
city: Gyeonggi-do
country: Korea, Republic of
facility: Research Site
city: Incheon
country: Korea, Republic of
facility: Research Site
city: Jinju-si
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
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city: Seoul
country: Korea, Republic of
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city: Suwon
country: Korea, Republic of
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city: Ulsan
country: Korea, Republic of
facility: Research Site
city: Kota Bharu
country: Malaysia
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city: Kuala Lumpur
country: Malaysia
facility: Research Site
city: Petaling Jaya
country: Malaysia
facility: Research Site
city: Pulau Pinang
country: Malaysia
facility: Research Site
city: Sabah
country: Malaysia
facility: Research Site
city: Amsterdam
country: Netherlands
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city: Bacolod
country: Philippines
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city: Baguio City
country: Philippines
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city: Cebu City
country: Philippines
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city: Cebu
country: Philippines
facility: Research Site
city: Davao City
country: Philippines
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city: Manila
country: Philippines
facility: Research Site
city: Quezon City
country: Philippines
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city: Quezon City
country: Philippines
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city: Quezon City
country: Philippines
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city: San Juan
country: Philippines
facility: Research Site
city: Bialystok
country: Poland
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city: Krakow
country: Poland
facility: Research Site
city: Olsztyn
country: Poland
facility: Research Site
city: Łódź
country: Poland
facility: Research Site
city: Chelyabinsk
country: Russian Federation
facility: Research Site
city: Moscow
country: Russian Federation
facility: Research Site
city: Saint Petersburg
country: Russian Federation
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city: Tomsk
country: Russian Federation
facility: Research Site
city: Singapore
country: Singapore
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city: Singapore
country: Singapore
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city: Badajoz
country: Spain
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country: Spain
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city: Barcelona
country: Spain
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country: Spain
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country: Spain
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city: Girona
country: Spain
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country: Spain
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country: Spain
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city: Madrid
country: Spain
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city: Madrid
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city: Majadahonda
country: Spain
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country: Spain
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country: Spain
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city: Sabadell
country: Spain
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city: Sevilla
country: Spain
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city: Valencia
country: Spain
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city: Zaragoza
country: Spain
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city: Baden
country: Switzerland
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city: Basel
country: Switzerland
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city: Bern
country: Switzerland
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city: Winterthur
country: Switzerland
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city: Zürich
country: Switzerland
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city: Chiayi
country: Taiwan
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city: Hsinchu
country: Taiwan
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city: Kaohsiung City
country: Taiwan
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city: Liuying
country: Taiwan
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city: Taichung
country: Taiwan
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city: Taichung
country: Taiwan
facility: Research Site
city: Taipei 112
country: Taiwan
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city: Taipei City
country: Taiwan
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city: Taipei
country: Taiwan
facility: Research Site
city: Bangkok
country: Thailand
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city: Bangkok
country: Thailand
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city: Chiang Mai
country: Thailand
facility: Research Site
city: Dusit
country: Thailand
facility: Research Site
city: Hat Yai
country: Thailand
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city: Muang
country: Thailand
facility: Research Site
city: Mueang Chanthaburi
country: Thailand
facility: Research Site
city: Adana
country: Turkey
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city: Ankara
country: Turkey
facility: Research Site
city: Edirne
country: Turkey
facility: Research Site
city: Istanbul
country: Turkey
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city: Istanbul
country: Turkey
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city: Izmir
country: Turkey
facility: Research Site
city: Bristol
country: United Kingdom
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city: Leicester
country: United Kingdom
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city: Liverpool
country: United Kingdom
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city: London
country: United Kingdom
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city: Manchester
country: United Kingdom
facility: Research Site
city: Newport
country: United Kingdom
facility: Research Site
city: Reading
country: United Kingdom
facility: Research Site
city: Wolverhampton
country: United Kingdom
facility: Research Site
city: Can Tho
country: Vietnam
facility: Research Site
city: Hanoi City
country: Vietnam
facility: Research Site
city: Hanoi
country: Vietnam
facility: Research Site
city: Hanoi
country: Vietnam
facility: Research Site
city: Ho Chi Minh city
country: Vietnam
facility: Research Site
city: Ho Chi Minh
country: Vietnam
facility: Research Site
Study officials:
affiliation: Shanghai Chest Hospital, Shanghai JiaoTong University, #241 Huai Hai Road (west), Shanghai, China.
name: Shun Lu, Prof,MD,PhD,
role: PRINCIPAL_INVESTIGATOR
References: