2024-511169-12-00招募中3 期
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)
适应症
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 87
- 试验地点
- 79
- 主要终点
- PFS as defined as time from randomisation until progression per RECIST 1.1 as assessed by BICR, or death due to any cause in participants with centrally confirmed MET IHC+ and/or MET FISH+ status (FAS). The comparison will include all randomised participants, as randomised, regardless of whether the participant withdraws from randomised therapy, receives another anti-cancer therapy, or clinically progresses prior to RECIST 1.1 progression.
研究概览
简要总结
To determine the efficacy of savolitinib in combination with osimertinib versus platinum doublet chemotherapy by assessment of PFS by BICR in participants with EGFR mutated, MET-overexpressed and/or amplified, locally advanced or metastatic NSCLC who have progressed on treatment with osimertinib.
研究设计
- 分配方式
- Randomized
- 主要目的
- Randomised, open-label study to investigate the efficacy and safety of savolitinib and osimertinib
- 盲法
- Single (Analyst)
入排标准
- 年龄范围
- 18 years 至 65+ years（65+ Years, 18-64 Years）
- 接受健康志愿者
- 是
入选标准
- •Provision of signed and dated written ICF prior to any mandatory and non-mandatory study-specific procedures, sampling and analyses.
- •ECOG performance status of 0 or
- •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.
- •Adequate haematological, liver, renal and cardiac functions, and coagulation parameters.
排除标准
- •Squamous NSCLC, and small cell lung cancer.
- •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.
- •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.
结局指标
主要结局
PFS as defined as time from randomisation until progression per RECIST 1.1 as assessed by BICR, or death due to any cause in participants with centrally confirmed MET IHC+ and/or MET FISH+ status (FAS). The comparison will include all randomised participants, as randomised, regardless of whether the participant withdraws from randomised therapy, receives another anti-cancer therapy, or clinically progresses prior to RECIST 1.1 progression.
PFS as defined as time from randomisation until progression per RECIST 1.1 as assessed by BICR, or death due to any cause in participants with centrally confirmed MET IHC+ and/or MET FISH+ status (FAS). The comparison will include all randomised participants, as randomised, regardless of whether the participant withdraws from randomised therapy, receives another anti-cancer therapy, or clinically progresses prior to RECIST 1.1 progression.
次要结局
- Overall survival defined as time from randomisation until the date of death due to any cause.
- Progression-free survival defined as time from randomisation until progression per RECIST 1.1 as assessed by BICR, or death due to any cause in centrally confirmed MET IHC+ population of FAS (FAS-IHC+).
- Overall survival defined as time from randomisation until the date of death due to any cause in FAS-IHC+.
- Progression-free survival defined as time from randomization until progression per RECIST 1.1 as assessed by investigator, or death due to any cause in centrally confirmed MET IHC+ population of FAS (FASIHC+).
- A/ Objective response rate will be based on BOR defined as the proportion of participants who have BOR of a CR or PR, as determined by BICR per RECIST 1.1. B/ Duration of response 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. C/Disease control rate defined as the proportion of participants who have BOR of a CR, PR, or stable disease [...]
- A/ TTD in pulmonary core symptoms (dyspnoea, cough, and chest pain) as measured by the questionnaire. B/TTD is defined as the time from randomisation until the date of deterioration.
- Plasma concentrations of savolitinib and its metabolites in the PK Analysis Set.
- Safety and tolerability will be evaluated in terms of AEs, SAEs, discontinuation rate due to AEs and deaths; clinical chemistry/haematology including LFTs; ECHOs/MUGAs, ECGs, ECOG performance status and vital signs in the Safety Analysis Set.
- 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 in the FAS population. • CNS ORR defined as the proportion of participants who have a BOR in the CNS by BICR assessment in the cFAS population. • 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 in the cFAS population.
研究者
Clinical Study Information Center
Scientific
AstraZeneca AB
研究点 (79)
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