Savolitinib Combine With Durvalumab in EGFR Wild-type Locally Advanced or Metastatic NSCLC

Study Overview
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Brief Summary
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This is an open-label, interventional, multiple-center, exploratory Phase II study sponsored by AstraZeneca Investment(China)Co., LTD. to evaluate the efficacy and safety of Savolitinib combine with Durvalumab in Chinese EGFR wild-type locally advanced or metastatic NSCLC patients with MET alteration.

Detailed Description
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Successfully enrolled, eligible patients will receive treatment of durvalumab (1500 mg, ivgtt, q4w) in combination with savolitinib (600mg for BW≥50kg, 400mg for BW<50kg, p.o., q.d.) after informed consent signed. Treatment will continue until either objective disease progression, unacceptable toxicity occurs, consent is withdrawn, other discontinuation criterion is met, or study completion. Tumor assessment is conducted according to RECIST 1.1. Baseline tumor assessments should include CT/MRI of chest and abdomen (including liver and adrenal glands) and should be performed within 28 days prior to receiving first dose of treatment. Follow-up assessments should be performed every 8 weeks (±7 days) after the start of treatment until 4 month, and then every 12 weeks until objective disease progression as defined by RECIST 1.1 even if a patient discontinues treatment prior to progression (unless they withdraw consent). Patients who have been observed CR or PR firstly will be scheduled for an additional visit to confirm efficacy at 4 weeks (+7 days) after the first assessment result of CR or PR was observed. Safety information should be visit in siteand will be prospectively collected from informed consent to the end of the follow-up period, defined as 3028 days (± 7 days) after last dose of Savolitinib, or 90 days (± 7 days) after last dose of Durvalumab which comes later.

Official Title
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Savolitinib Combine With Durvalumab in Chinese EGFR Wild-type Locally Advanced or Metastatic NSCLC Patients With MET Alteration: An Open-label, Interventional, Multiple-center, Exploratory Trial (SOUND)

Conditions
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Lung Cancer

Intervention / Treatment
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* Drug: Savolitinib
* Drug: Durvalumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Female or male patients aged 18 years or over NSCLC with the following features: locally advanced or metastatic NSCLC EGFR wild-type MET Exon 14 skipping mutation, or MET overexpression, or MET amplification based on FISH or NGS Tissue sample / liquid sample available Patients must have measurable disease per RECIST 1.1 World Health Organization (WHO) performance status 0 or 1 at enrollment Adequate hematological, liver, renal functions Adequate coagulation parameters A minimum life expectancy of 12 weeks Ability to swallow and retain oral medications. Ability and willingness to comply with the study and follow-up Informed consent Exclusion Criteria History of allogeneic organ transplantation. Active gastrointestinal disease or other condition that will interfere significantly with the absorption, distribution, metabolism, or excretion of oral therapy severe cardiac diseases in 6 months, clinically important abnormalities in QT interval & ECGs Uncontrolled hypertension radiotherapy administered ≤28 days before 1st-dose, or has not recovered from side effects Spinal cord compression or symptomatic brain metastases Hypersensitivity to durvalumab or savolitinib or drugs with a similar chemical structure or class Prior exposure to any immune-mediated therapy or MET inhibitor Active or prior documented autoimmune or inflammatory disorders Major surgical procedures ≤28 days of 1st-dose or minor surgical procedures ≤7 days Serious underlying medical condition, serious active infection, uncontrolled intercurrent illness Active hepatitis B or hepatitis C. Active cancers, or history of treatment for invasive cancer, within the last 5 years Receipt of live attenuated vaccine within 30 days prior to the first dose of study treatment Women who are either pregnant or breast-feeding Participation in another clinical study with an investigational product administered in 3 months Judgment by the investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions and requirements
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Savolitinib combine with Durvalumab<br>single-arm | Drug: Savolitinib<br>* Savolitinib combine with Durvalumab<br>Drug: Durvalumab<br>* savolitinib plus durvalumab<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PFS | PFS (Progression-Free Survival ) will be defined as the time from first dose of study intervention until progression per RECIST 1.1 as assessed by the investigator or death due to any cause prior to progressive disease. | The analysis will occur when 60 percent PFS event is observed in each cohort, at approximately 10 months after last patient in. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ORR | ORR(Objective Response Rate) defined as the proportion of participants who achieved a CR (Complete Response) or PR(Partial response) as their best overall response based on Response Evaluation Criteria in Solid Tumors (RECIST)1.1 as assessed by the investigator. | The analysis will occur at two months after last patient in. | 
| DoR | DoR(Duration of Response)is defined as the time from the date of first documented response until date of documented progression or death in the absence of disease progression (ie, date of PFS (Progression-Free Survival ) event or censoring-date of first response+1). | The analysis will occur when 60 percent PFS event is observed in each cohort, at approximately 10 months after last patient in. | 
| DCR | DCR (Disease Control Rate)is defined as the number(percent)of subjects with at least one visit response of confirmed CR (Complete Response), PR (Partial Response) or SD(Stable Disease), based on based on Investigator assessment according to RECIST 1.1. | The analysis will occur at two months after last patient in. | 
| OS | OS(Overall Survival) is defined as the time from the start of treatment until death due to any cause. Any patient not known to have died at the time of analysis will be censored based on the last recorded date on which the patient was known to be alive. | The analysis will occur when 60 percent PFS event ratio is observed in each cohort, at approximately 10 months after last subject in, up to a maximum of approximately 3 years after first subject in. |