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).
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 发起方
- AstraZeneca
- 入组人数
- 341
- 试验地点
- 214
- 主要终点
- 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.
研究概览
简要总结
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.
详细描述
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Criteria in Solid Tumours 1.1 (RECIST 1.1) is assessed by the investigator, unacceptable toxicity occurs, consent is withdrawn, or another discontinuation criterion is met.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 130 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
- •Adequate haematological, liver, renal and cardiac functions, and coagulation parameters.
- •ECOG performance status of 0 or 1.
排除标准
- •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.
研究组 & 干预措施
Chemotherapy
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
干预措施: Carboplatin (Drug)
Savolitinib + Osimertinib
300 mg savolitinib BID plus 80 mg osimertinib QD
干预措施: Osimertinib (Drug)
Chemotherapy
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
干预措施: Cisplatin (Drug)
Chemotherapy
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
干预措施: Pemetrexed (Drug)
Savolitinib + Osimertinib
300 mg savolitinib BID plus 80 mg osimertinib QD
干预措施: Savolitinib (Drug)
结局指标
主要结局
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.
时间窗: 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.
次要结局
- 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.)
- 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)
- Pharmacokinetics (PK) of savolitinib.(Approximately 36.5 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)
- 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.(Approximately 55 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.(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(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.(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.(Approximately 55 months post first subject randomized)