Study on Savolitinib Combined With Osimertinib in Treatment of Advanced NSCLC With MET Amplification

Phase 3

Recruiting

• Conditions: Non-small Cell Lung Cancer
• Interventions: Drug: Savolitinib + Osimertinib; Drug: Pemetrexed + Cisplatin /Carboplatin

• Registration Number: NCT05015608
• Lead Sponsor: Hutchison Medipharma Limited

Brief Summary

This study will look at how effective the study drug(Savolitinib combined with Osimertinib) versus Pemetrexed combined with platinum in treatment of patients with locally advanced or metastatic NSCLC with MET amplification after failure of the first-line EGFR inhibitor therapy.

Detailed Description

This is a multicenter, randomized, controlled, open, phase III clinical study to evaluate the clinical efficacy and safety of Savolitinib combined with Osimertinib in treatment of patients with locally advanced or metastatic NSCLC with MET amplification after failure of EGFR inhibitor therapy.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations
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Related News

Study Timeline

• Study First Submitted: 2021-07-30
• Study First Submitted QC: 2021-08-16
• Study First Posted: 2021-08-20
• Study Start: 2021-11-22
• Status Verified: 2023-03
• Last Update Submitted: 2023-03-29
• Last Update Posted: 2023-03-30
• Primary Completion: 2024-09-15
• Study Completion: 2024-11-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 250

Inclusion Criteria

1. Fully aware this study and voluntary to sign the informed consent form, and willing and able to comply with the study procedure;
2. Age ≥ 18 and ≤75 years;
3. In accordance with the 8th Edition of TNM staging for lung cancers by International Association for the Study of Lung Cancer and American Joint Committee on Cancer, patients with histologically or cytologically confirmed unresectable and non-suitable for radical concurrent chemoradiotherapy, locally advanced or metastatic (stage IIIB, IIIC or IV) NSCLC;
4. EGFR sensitive mutations prior to the first-line EGFR-TKI therapy;
5. Radiologically documented disease progression after the first-line EGFR-TKI;
6. MET amplification after disease progression following the first-line therapy;
7. Having measurable lesions (in accordance with RECIST 1. 1 criteria);
8. United States Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1;
9. Expected survival >12 weeks;
10. Adequate bone marrow reserve or organ function
11. Female patients of childbearing potential must agree to use effective contraceptive methods from screening period to 4 weeks after discontinuation of the study drug;
12. Male subjects should be willing to agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures and agreement to refrain from donating sperm. ;
13. Being able to take or swallow the drug orally.

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Exclusion Criteria

1. Patients with positive T790M mutations;
2. Previous treatment for c-MET;
3. Currently having other malignant tumors, or having other infiltrating malignant tumors in the past 5 years.;
4. Previous use of systematic antitumor therapy other than EGFR-TKI for advanced NSCLC;
5. Currently having received antiangiogenic therapy or traditional Chinese medicine with antitumor indication、extensive radiotherapy 、palliative local radiotherapy, a major surgery,or participated in other drug clinical trials and received corresponding tudy drug etc;
6. Currently receiving the potent CYP3A4 inducers or potent CYP1A2 inhibitors within two weeks prior to the start of study treatment;
7. Having not been sufficiently recovered from the toxicity and/or complication resulting from any interventional measure prior to the start of treatment;
8. Clinically significant active infection, including but not limited to tuberculosis, human immunodeficiency virus (HIV) infection (positive HIV1/2 antibody);
9. Active hepatitis B, or active hepatitis C;
10. Acute myocardial infarction, unstable angina pectoris, stroke or transient ischemic attack;
11. Known cancerous thrombus or deep vein thrombosis or uncontrollable hypertension despite the use of drugs;
12. Mean resting corrected QT interval (QTcF) or Any important abnormality in rhythm;
13. Presence of meningeal metastases, spinal cord compression or active brain metastases prior to the start of study treatment;
14. Active gastrointestinal disease or other conditions significantly affecting the absorption, distribution, metabolism or excretion of oral study drug;
15. Lack of compliance with participation in this clinical study or inability to comply with the limitations and requirements of the study, as judged by investigators;
16. Known allergy to the active or inactive ingredient of Savolitinib or Osimertinib;
17. Previous history of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis and any active interstitial lung disease;
18. Pregnant or breastfeeding women;

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Savolitinib + Osimertinib	Savolitinib + Osimertinib	Savolitinib orally once per day (QD) + Osimertinib orally QD,21day cycles (every 3 weeks)
Pemetrexed combined with platinum	Pemetrexed + Cisplatin /Carboplatin	Pemetrexed combined with platinumon on Day 1 of 21day cycles (every 3 weeks)

Primary Outcome Measures

Name	Time	Method
PFS	5 months after the last patient enrolled	Progression-free survival (PFS) using Investigator assessment as defined by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1).

Secondary Outcome Measures

Name	Time	Method
Duration of Response (DoR)	5 months after the last patient enrolled	the duration between the date the criteria for complete response or partial response was first measured (first record shall prevail) and the date of disease recurrence or progression as objectively recorded
Overall survival (OS)	5 months after the last patient enrolled	the time from the date of randomization to the date of death (all causes)
The objective response rate of the tumor (ORR)	5 months after the last patient enrolled	the incidence of confirmed complete response or partial response
PFS	5 months after the last patient enrolled	Progression-free survival (PFS) using IRC as defined by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1)
Safety and tolerability	5 months after the last patient enrolled	Incidence and nature of treatment emergent adverse events (TEAE), the other safety variables including physical examination, vital signs and laboratory examinations
The disease control rate (DCR)	5 months after the last patient enrolled	the incidence of complete response, partial response and stable disease
Time to Response (TTR)	5 months after the last patient enrolled	the period from the date of randomization to the date when the criteria for complete response or partial response was first measured (first record shall prevail).

Trial Locations

Locations (1)

Shanghai Chest Hospital; 🇨🇳 Shanghai, Shanghai, China