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

NCT05374603 | Active Not Recruiting Phase 2

• 1 other identifier: D5083C00002
• Study Type: interventional
• Target: 47
• Locations: 1 country
• Sites: 16

Brief 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.

Conditions

Lung Cancer

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• ORR

  The analysis will occur at two months after last patient in.

• DoR

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

• DCR

  The analysis will occur at two months after last patient in.

• OS

  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.

Other Outcomes (3)

• PD-L1 expression

  The analysis will occur at two months after last patient in.

• Gene profile

  The analysis will occur when 60 percent PFS event is observed in each cohort.

• Potential molecular resistance mechanism

  The analysis will occur when 60 percent PFS event is observed in each cohort.

Study Arms (1)

Savolitinib combine with Durvalumab

EXPERIMENTAL

single-arm

Drug: Savolitinib; Drug: Durvalumab

Interventions

Savolitinib DRUG

Savolitinib combine with Durvalumab

Savolitinib combine with Durvalumab

Durvalumab DRUG

savolitinib plus durvalumab

Savolitinib combine with Durvalumab

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• 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).

You may not qualify if:

• 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)
• 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.

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (16)

Research Site

Beijing, 100021, China

Location

Research Site

Beijing, 100039, China

Location

Research Site

Beijing, CN-100730, China

Location

Research Site

Changsha, 410011, China

Location

Research Site

Chongqing, 400010, China

Location

Research Site

Hangzhou, 310003, China

Location

Research Site

Hangzhou, 310009, China

Location

Research Site

Jinan, 250021, China

Location

Research Site

Kunming, 650118, China

Location

Research Site

Nanchang, 330006, China

Location

Research Site

Ningbo, 315100, China

Location

Research Site

Shanghai, 200030, China

Location

Research Site

Wenzhou, 325000, China

Location

Research Site

Wuhan, 430022, China

Location

Research Site

Wuhan, 430030, China

Location

Research Site

Zhengzhou, 450000, China

Location

MeSH Terms

Conditions

Lung Neoplasms

Interventions

1-(1-(imidazo(1,2-a)pyridin-6-yl)ethyl)-6-(1-methyl-1H-pyrazol-4-yl)-1H-(1,2,3)triazolo(4,5-b)pyrazine; durvalumab

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Shun Lu, Doctor

  Shanghai Chest Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 29, 2022
• First Posted: May 16, 2022
• Study Start: November 15, 2022
• Primary Completion (Estimated): January 18, 2027
• Study Completion (Estimated): January 18, 2027
• Last Updated: January 21, 2026

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrails.pharmacm.com/ST/Submission/Disclosure.
• Access Criteria: When a request has been approved AstraZeneca will provide access to the deidentified individual patient-level data in approved sponsored tool. Signed Data Sharing Agreement(non-negotiable contract for data accessors)must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MES to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrails.pharmacm.com/ST/Submission/Disclosure.

Locations

CN (16)