Lung CancerPhase 2SOUNDNCT05374603

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

A Phase 2 study testing Savolitinib and Durvalumab in people with Lung Cancer, run by AstraZeneca at 16 sites in China.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Trial summary

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. Read more about this study

Who is it for?: Any age
Conditions the study is for: Lung Cancer
What is being tested?: Savolitinib and Durvalumab
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 47 participants
Where: 16 sitesChina
Study dates: 15 Nov 2022to 18 Jan 2027
Phase: Phase 2

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages Any age
All sexes
No healthy volunteers
Child, Adult, Older adult

Who may be able to join

Participants are eligible to be included in the study only if all of the following criteria apply:
Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
Provision of signed and dated, written ICF prior to any mandatory study specific procedures, sampling, and analyses.
Females and/or males age ≥18 years at the time of signing the ICF.
Body weight >30 kg
NSCLC with the following features:

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Histologically or cytologically confirmed locally advanced or metastatic NSCLC
EGFR wild-type
MET Exon 14 skipping mutation, or MET overexpression (IHC 3+ in ≥70% of tumor cells), or MET amplification based on FISH (GCN≥5 or MET/CEP7≥2) or NGS (≥20% tumor cells, coverage of ≥200 × sequencing depth and ≥5 copies of MET over tumor ploidy)
WHO/Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 with no deterioration over the previous 2 weeks prior to baseline or day of first dosing
A minimum life expectancy of 12 weeks at the time of signing the ICF.
Patients must have received no more than 2 system anti-cancer treatment at the time of signing the ICF.
Patients must have measurable disease per RECIST 1.1, as defined by at least 1 lesion that can be accurately measured at baseline as ≥10 mm at the longest diameter (except lymph nodes which must have a short axis ≥15 mm) with computed tomography (CT) or magnetic resonance imaging (MRI), which is suitable for accurate repeated measurements.
Adequate haematological function defined as:
Haemoglobin ≥9 g/dL (no transfusion in the past 2 weeks).
Absolute neutrophil count ≥1.5×109/L.
Platelet count ≥100,000/μL (no transfusion in the past 10 days)
Adequate liver function defined as:
Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 x the upper limit of normal (ULN) with total bilirubin TBL ≤1 x ULN
OR TBL >1 x ULN to ≤1.5x ULN with ALT and AST ≤ 1 x ULN
Adequate renal function defined as a serum creatinine <1.5 times the institutional ULN OR a glomerular filtration rate ≥50 mL/min, as assessed using the standard methodology at the investigating centre (eg, Cockcroft-Gault, Modification of Diet in Renal Disease or Chronic Kidney Disease Epidemiology Collaboration formulae, ethylenediaminetetraacetic acid clearance or 24-hour urine collection). Confirmation of creatinine clearance is only required when creatinine is >1.5 times ULN.
Adequate coagulation parameters, defined as: International Normalisation Ratio (INR) <1.2 x ULN and activated partial thromboplastin time (aPTT) <1.2 x ULN unless patients are receiving therapeutic anticoagulation which affects these parameters
Patients with known tumour thrombus or deep vein thrombosis are eligible if clinically stable on low molecular weight heparin (LMWH) for ≥2 weeks.
Ability to swallow and retain oral medications.
Willingness and ability to comply with study and follow-up procedures.
Females of childbearing potential should be willing to use adequate contraceptive measures (see Section 5.3.1), should not be breast feeding, and must have a negative pregnancy test if of childbearing potential or must have evidence of non-childbearing potential by fulfilling one of the following criteria at screening:
Post-menopausal is defined as aged more than 50 years and amenorrhoeic for at least 12 months following cessation of all exogenous hormonal treatments; women under the age of 50 years would be considered postmenopausal if they have been amenorrhoeic for 12 months or more following cessation of exogenous hormonal treatments and with LH and FSH levels in the post-menopausal range for the institution; or women with documentation of irreversible surgical sterilisation by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation.
Further information is available in Appendix G (Contraception Requirements).
Male patients with a female partner of childbearing potential should be willing to use barrier contraception during the study and for 6 months following discontinuation of study drug. Patients should refrain from donating sperm from the start of dosing until 6 months after discontinuing study treatment.

Who cannot join

Participants are excluded from the study if any of the following criteria apply:
As judged by the investigator, active gastrointestinal disease or other condition that will interfere significantly with the absorption, distribution, metabolism, or excretion of oral therapy (eg, ulcerative disease, uncontrolled nausea, vomiting, diarrhoea Grade≥2, malabsorption syndrome or previous significant bowel resection). therapy (eg, ulcerative disease, uncontrolled nausea, vomiting, diarrhoea Grade
≥2, malabsorption syndrome or previous significant bowel resection).
Any of the following cardiac diseases diagnosed currently or within the last 6 months:
Unstable angina pectoris
Congestive heart failure (New York Heart Association [NYHA] ≥Grade 2)

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Acute myocardial infarction
Stroke or transient ischemic attack
Ventricular arrhythmias
Uncontrolled hypertension (BP ≥150/95 mmHg despite medical therapy) ≤28 days of beginning study drug.
Mean resting correct QT interval (QTcF) >470 msec for women and >450 msec for men at Screening, obtained from 3 ECGs using the screening clinic ECG machine derived QTcF value.
(a)Any factors that may increase the risk of QTcF prolongation or risk of arrhythmic events such as heart failure, chronic hypokalaemia not correctable with supplements, congenital or familial long QT syndrome, family history of unexplained sudden death under 40 years of age in first-degree relatives or any concomitant medication known to prolong the QT interval and cause Torsade de Pointes.
Any clinically important abnormalities in rhythm, conduction or morphology of resting ECGs ≤28 days of beginning study drug, eg, complete left bundle branch block, third degree heart block, second degree heart block, P-R interval >250 msec.
Acute coronary syndrome diagnosed currently or within the last 6 months.
Wide field radiotherapy (including therapeutic radioisotopes such as strontium 89) administered ≤28 days or limited field radiation for palliation ≤7 days prior to starting study drug or has not recovered from side effects of such therapy.
Major surgical procedures ≤28 days of beginning study drug or minor surgical procedures ≤7 days.
Active hepatitis B (HBV) (positive HBV surface antigen [HBsAg] result) or hepatitis C (HCV). Viral testing is not required for assessment of eligibility for the study. Patients with a past or resolved HBV or HCV infection are eligible if:
Negative for HBsAg and positive for hepatitis B core antibody [anti-HBc] or
Positive for HBsAg, but for >6 months have had normal transaminases and HBV DNA levels between 0 to 2000 IU/mL (inactive carrier state) and willing to start and maintain antiviral treatment for at least the duration of the study.
Patients with a past or resolved HBV infection must have monthly monitoring of ALT and HBV DNA
HBV DNA levels >2000 IU/mL but on prophylactic antiviral treatment for the past 3 months and must maintain the antiviral treatment during the study.
Patients with positive HCV antibody are eligible only if the polymerase chain reaction is negative for HCV ribonucleic acid.
History of liver cirrhosis of any origin and clinical stage; or history of other serious liver disease or chronic disease with relevant liver involvement, with or without normal LFTs*, such as
Hemochromatosis
Alpha-1 Antitrypsin deficiency
Autoimmune hepatitis (AIH)
Primary sclerosing cholangitis (PSC)
Primary biliary cirrhosis (PBC)
Biopsy-confirmed Non-Alcoholic Steatohepatitis (NASH) with advanced fibrosis
Biopsy- confirmed Alcoholic Steatohepatitis with advanced fibrosis
Wilson's disease.
Hepatocellular carcinoma* Patients with liver metastases are eligible, provided they meet other eligibility criteria, including liver biochemistry criteria.
Presence of other active cancers, or history of treatment for invasive cancer, within the last 5 years. Patients with Stage I cancer who have received definitive local treatment at least 3 years previously, and are considered unlikely to recur are eligible. All patients with previously treated in situ carcinoma (ie, non-invasive) are eligible, as are patients with history of non-melanoma skin cancer.
Having gene mutations sensitive to targeted drugs for EGFR, ALK and ROS-1.
Unresolved toxicities from any prior therapy greater than Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 at the time of starting study treatment with the exception of alopecia
Spinal cord compression or brain metastases unless asymptomatic, stable, and not requiring steroids for at least 2 weeks prior to start of study intervention. Subjects with leptomeningeal metastases are ineligible.
Past medical history of ILD, drug-induced ILD, radiation pneumonitis which required steroid treatment, or any evidence of clinically active ILD.
Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [eg, colitis or Crohn's disease], diverticulitis [with the exception of diverticulosis], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc].
The following are exceptions to this criterion:
Patients with vitiligo or alopecia
Patients with hypothyroidism (eg, following Hashimoto syndrome) stable on hormone replacement
Any chronic skin condition that does not require systemic therapy
Patients without active disease in the last 5 years may be included but only after consultation with the Study Physician
Patients with celiac disease controlled by diet alone
Known serious active infection including, but not limited to, tuberculosis, or human immunodeficiency virus (positive human immunodeficiency virus 1/2 antibodies). Testing is not required for assessment of eligibility for the study.
Known contraindications to durvalumab administration.
Known hypersensitivity to the active or inactive excipients of durvalumab or savolitinib or drugs with a similar chemical structure or class.
Prior exposure to immune-mediated therapy including, but not limited to, other anti CTLA-4, anti-PD-1, anti-PD-L1, and anti-programmed cell death ligand 2 (anti-PD-L2) antibodies, excluding therapeutic anticancer vaccines.
Prior exposure to any HGF/MET inhibitor, e.g., foretinib, crizotinib, cabozantinib, merestinib, onartuzumab, capmatinib, tepotinib, etc.
As judged by the investigator, any evidence of severe or uncontrolled systemic diseases, including renal transplant, active bleeding diatheses or uncontrolled hypertension, which in the investigator's opinion makes it undesirable for the patient to participate in the trial or which would jeopardise compliance with the protocol.
Receipt of the last dose of anticancer therapy (chemotherapy, immunotherapy, targeted therapy, biologic therapy, tumor embolisation, or monoclonal antibodies) of early stage NSCLC within 14 days prior to the first dose of study intervention.
Participation in another clinical study with a study intervention or investigational medicinal device administered in the last 30 days prior to the first dose of study intervention or concurrent enrolment in another clinical study, unless it is an observational (noninterventional) clinical study or during the off-treatment follow-up period of an interventional study.
Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site).
Judgment by the investigator that the participant should not participate in the study if the participant is unlikely to comply with study procedures, restrictions and requirements.
Previous enrolment in the present study.
Without civil capacity or with restricted civil capacity.
Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab. The following are exceptions to this criterion:
Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra articular injection)
Systemic corticosteroids at physiologic doses not to exceed <<10 mg/day>> of prednisone or its equivalent
Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication)
Receipt of live attenuated vaccine within 30 days prior to the first dose of durvalumab. Note: Patients, if enrolled, should not receive live vaccine whilst receiving durvalumab and up to 30 days after the last dose of durvalumab
Any other reasons judged by the leading investigator to prevent the subject from participating in this study
Patients currently receiving (or unable to stop use prior to receiving the first dose of study treatment) medications or herbal supplements known to be strong inducers of CYP3A4, strong inhibitors of CYP1A2, within 2 weeks of the first dose of study treatment (3 weeks for St John's Wort) will be excluded.

Trial locations and contacts

16 sites in 1 country.

City, postcode or hospital

16 sites in 1 country

China16 sites

Research Site
Beijing, 100021
Research Site
Beijing, 100039
Research Site
Beijing, CN-100730
Research Site
Changsha, 410011
Research Site
Chongqing, 400010
Research Site
Hangzhou, 310003
Research Site
Hangzhou, 310009
Research Site
Jinan, 250021
Research Site
Kunming, 650118
Research Site
Nanchang, 330006
Research Site
Ningbo, 315100
Research Site
Shanghai, 200030
Research Site
Wenzhou, 325000
Research Site
Wuhan, 430022
Research Site
Wuhan, 430030
Research Site
Zhengzhou, 450000

Other trials in China

About this study

Official title: 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)

Read the detailed description

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.

Conditions: Lung Cancer
Being tested: Savolitinib, Durvalumab
Medical subject headings: Lung Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

SavolitinibDrug
Savolitinib combine with Durvalumab
DurvalumabDrug
savolitinib plus durvalumab

Study groups in NCT05374603
Study group	Role	What they receive
Savolitinib combine with Durvalumab	Experimental	single-arm Receives: Drug: Savolitinib; Drug: Durvalumab

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: The analysis will occur when 60 percent PFS event is observed in each cohort, at approximately 10 months after last patient in.

Secondary outcomes (4)

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.
Measured: 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).
Measured: 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.
Measured: 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.
Measured: 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.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

15 Nov 202218 Jan 2027

First posted16 May 2022
Study start15 Nov 2022
Primary completion18 Jan 2027 (estimated)
Study completion18 Jan 2027 (estimated)

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for Lung CancerStudies of the same condition, open and under way.
More trials run by AstraZenecaThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 47 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT05374603
Sponsor's protocol ID: D5083C00002
Acronym: SOUND
Status last verified: Sep 2026
First submitted: 29 Apr 2022
Last updated: 3 Sep 2026
Results posted: No
Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: Yes: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trails via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrails.pharmacm.com/ST/Submission/Disclosure. Indicates that AZ accepting requests for IPD, but this does not mean all requests will be shared.