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

NCT ID: NCT05015608

Last Updated: 2025-05-23

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 250 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-11-22
• Study Completion Date: 2025-12-30

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.

Conditions

Non-small Cell Lung Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Savolitinib + Osimertinib

Savolitinib orally once per day (QD) + Osimertinib orally QD,21day cycles (every 3 weeks)

Group Type: EXPERIMENTAL

Savolitinib + Osimertinib

Intervention Type: DRUG

Subjects will receive Savolitinib orally once per day (QD) + Osimertinib orally QD,21day cycles (every 3 weeks) until disease progression, death, adverse event (AE) leading to discontinuation or withdrawal of consent.

Pemetrexed combined with platinum

Pemetrexed combined with platinumon on Day 1 of 21day cycles (every 3 weeks)

Group Type: ACTIVE_COMPARATOR

Pemetrexed + Cisplatin /Carboplatin

Intervention Type: DRUG

Pemetrexed combined with platinumon on Day 1 of 21day cycles (every 3 weeks)

Interventions

Savolitinib + Osimertinib

Subjects will receive Savolitinib orally once per day (QD) + Osimertinib orally QD,21day cycles (every 3 weeks) until disease progression, death, adverse event (AE) leading to discontinuation or withdrawal of consent.

Intervention Type: DRUG

Pemetrexed + Cisplatin /Carboplatin

Pemetrexed combined with platinumon on Day 1 of 21day cycles (every 3 weeks)

Intervention Type: DRUG

Eligibility Criteria

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.

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;

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hutchison Medipharma Limited

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Shun Lu, MD

Role: PRINCIPAL_INVESTIGATOR

Shanghai Chest Hospital

Jie Wang, MD

Role: PRINCIPAL_INVESTIGATOR

Cancer Institute and Hospital, Chinese Academy of Medical Sciences

Locations

Shanghai Chest Hospital

Shanghai, Shanghai Municipality, China

Countries

China

Other Identifiers

2020-504-00CH3

Identifier Type: -

Identifier Source: org_study_id