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

NCT05015608 | Active Not Recruiting Phase 3 DMC

• 1 other identifier: 2020-504-00CH3
• Study Type: interventional
• Target: 250
• Locations: 1 country
• Sites: 1

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.

Conditions

Non-small Cell Lung Cancer

Outcome Measures

Primary Outcomes (1)

• PFS

  Progression-free survival (PFS) using Investigator assessment as defined by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1).

  5 months after the last patient enrolled

Secondary Outcomes (7)

• Safety and tolerability

  5 months after the last patient enrolled

• The objective response rate of the tumor (ORR)

  5 months after the last patient enrolled

• The disease control rate (DCR)

  5 months after the last patient enrolled

• Duration of Response (DoR)

  5 months after the last patient enrolled

• Overall survival (OS)

  5 months after the last patient enrolled

Study Arms (2)

Savolitinib + Osimertinib

EXPERIMENTAL

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

Drug: Savolitinib + Osimertinib

Pemetrexed combined with platinum

ACTIVE COMPARATOR

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

Drug: Pemetrexed + Cisplatin /Carboplatin

Interventions

Savolitinib + Osimertinib 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.

Savolitinib + Osimertinib

Pemetrexed + Cisplatin /Carboplatin DRUG

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

Pemetrexed combined with platinum

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Fully aware this study and voluntary to sign the informed consent form, and willing and able to comply with the study procedure;
• Age ≥ 18 and ≤75 years;
• 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;
• EGFR sensitive mutations prior to the first-line EGFR-TKI therapy;
• Radiologically documented disease progression after the first-line EGFR-TKI;
• MET amplification after disease progression following the first-line therapy;
• Having measurable lesions (in accordance with RECIST 1. 1 criteria);
• United States Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1;
• Expected survival \>12 weeks;
• Adequate bone marrow reserve or organ function
• Female patients of childbearing potential must agree to use effective contraceptive methods from screening period to 4 weeks after discontinuation of the study drug;
• 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. ;
• Being able to take or swallow the drug orally.

You may not qualify if:

• Patients with positive T790M mutations;
• Previous treatment for c-MET;
• Currently having other malignant tumors, or having other infiltrating malignant tumors in the past 5 years.;
• Previous use of systematic antitumor therapy other than EGFR-TKI for advanced NSCLC;
• 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;
• Currently receiving the potent CYP3A4 inducers or potent CYP1A2 inhibitors within two weeks prior to the start of study treatment;
• Having not been sufficiently recovered from the toxicity and/or complication resulting from any interventional measure prior to the start of treatment;
• Clinically significant active infection, including but not limited to tuberculosis, human immunodeficiency virus (HIV) infection (positive HIV1/2 antibody);
• Active hepatitis B, or active hepatitis C;
• Acute myocardial infarction, unstable angina pectoris, stroke or transient ischemic attack;
• Known cancerous thrombus or deep vein thrombosis or uncontrollable hypertension despite the use of drugs;
• Mean resting corrected QT interval (QTcF) or Any important abnormality in rhythm;
• Presence of meningeal metastases, spinal cord compression or active brain metastases prior to the start of study treatment;
• Active gastrointestinal disease or other conditions significantly affecting the absorption, distribution, metabolism or excretion of oral study drug;
• 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;

Sponsors & Collaborators

• Hutchison Medipharma Limited: lead

Study Sites (1)

Shanghai Chest Hospital

Shanghai, Shanghai Municipality, 210000, China

Location

Related Publications (1)

• Lu S, Wang J, Yang N, Lv D, Chen L, Wu L, Li X, Sun L, Yu Y, Jin B, Yang L, Guo Y, Xu H, Yi T, Zeng A, Dong X, Chen J, Wang Z, Niu H, Cheng Y, Pan P, Deng P, Pan H, Min X, Bai J, Liu L, Zhang T, Li J, Fan S, Shi MM, Mok T, Su W; SACHI Study Group. Savolitinib plus osimertinib versus chemotherapy for advanced, EGFR mutation-positive, MET-amplified non-small-cell lung cancer in China (SACHI): interim analysis of a multicentre, open-label, phase 3 randomised controlled trial. Lancet. 2026 Jan 13:S0140-6736(25)01811-2. doi: 10.1016/S0140-6736(25)01811-2. Online ahead of print.

  PMID: 41544643 DERIVED

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

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; osimertinib; Pemetrexed; Cisplatin; Carboplatin

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Coordination Complexes; Organic Chemicals

Study Officials

• Shun Lu, MD

  Shanghai Chest Hospital

  PRINCIPAL INVESTIGATOR

• Jie Wang, MD

  Cancer Institute and Hospital, Chinese Academy of Medical Sciences

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 30, 2021
• First Posted: August 20, 2021
• Study Start: November 22, 2021
• Primary Completion: December 15, 2025
• Study Completion: December 30, 2025
• Last Updated: May 23, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)