Non-small Cell Lung Cancer
Conditions
Brief summary
A Phase III Clinical Study on Savolitinib Combined with Osimertinib in Treatment of EGFRm+/MET+ Locally Advanced or Metastatic Non-small Cell Lung Cancer
Detailed description
A Multicenter, Randomized, Double-blind, Phase III Clinical Study to Evaluate the Efficacy and Safety of Savolitinib Combined with Osimertinib versus Placebo Combined with Osimertinib as the First-line Therapy for Patients with EGFRm+/MET+ Locally Advanced or Metastatic Non-small Cell Lung Cancer
Interventions
DRUGSavolitinib
Subjects will receive Savolitinib 600 mg or 400 mg daily (including 600/400 mg QD or 300/200 mg BID) orally + Osimertinib 80 mg QD orally ( every 3 weeks), 21day cycles (every 3 weeks) until disease progression, death, adverse event (AE) leading to discontinuation or withdrawal of consent.
DRUGPlacebo
Subjects will receive Placebo 600 mg or 400 mg daily (including 600/400 mg QD or 300/200 mg BID) orally + Osimertinib 80 mg QD orally ( every 3 weeks), 21day cycles (every 3 weeks) until disease progression, death, adverse event (AE) leading to discontinuation or withdrawal of consent.
Sponsors
Hutchmed
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
This study plans to enroll 412 patients, among them, there are 92 subjects in Savolitinib/Placebo QD administration; and about 320 subjects in Savolitinib/Placebo BID administration will be randomized in a ratio of 1 to 1 into the study group and the control group. Study group: Savolitinib 600 mg or 400 mg daily (including 600/400 mg QD or 300/200 mg BID) orally + Osimertinib 80 mg QD orally Control group: Placebo 600 mg or 400 mg daily (including 600/400 mg QD or 300/200 mg BID) orally+ Osimertinib 80 mg QD orally
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Fully aware of this study and voluntary to sign the informed consent form, and being willing and able to comply with the study procedure; 2. Age ≥ 18 3. In accordance with the Eighth Edition of TNM Staging of Lung Cancer by the International Association for the Study of Lung Cancer and American Joint Committee on Cancer, and patients with histologically or cytologically confirmed unresectable locally advanced (stage ⅢB/ⅢC), metastatic or recurrent (stage IV) NSCLC who are not suitable for radical concurrent chemoradiotherapy; 4. Carrying two common EGFR mutations clearly related with the sensitivity to EGFR-TKI (i.e., exon 19 deletion, and L858R) and c-MET overexpression 5. Having measurable lesions (in accordance with RECIST 1.1 criteria); 6. ECOG Performance Status score 0 or 1, or Karnofsky score ≥80; 7. Survival is expected to exceed 12 weeks; 8. No any previous systematic antitumor therapy for advanced/metastatic disease; 9. adequate bone marrow reserve or organ function 10. Female patients of childbearing potential must agree to use effective contraceptive methods from screening period to 6 weeks after discontinuation of the study drug , and agree not to donate ova (oocytes) for reproductive purposes during this period; 11. Male patients whose sexual partners are women of childbearing potential must use condoms during sexual intercourse during the study and within 6 months after discontinuation of study drug 12. Being able to take or swallow the drug orally.
Exclusion criteria
1. Previous treatment with EGFR inhibitors or MET inhibitors; 2. Currently having other malignant tumors, or having other infiltrating malignant tumors in the past 5 years; 3. Antitumor therapy within 2 weeks prior to the start of study treatment, including hormone therapy, biotherapy, immunotherapy or the traditional Chinese medicine for antitumor indication; 4. Having received extensive radiotherapy (including radionuclide therapy, e.g., Sr-89) within 4 weeks prior to the start of study treatment or palliative local radiotherapy within one week prior to the start of study treatment, or the above adverse reactions of radiotherapy did not recover; 5. Having received a major surgery within 4 weeks prior to the start of study treatment or a minor surgery (except biopsy, and venous catheterization) within one week prior to the start of study treatment; 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. Uncontrollable hypertension despite the use of drugs, 12. Mean resting corrected QT interval (QTcF) or Any important abnormality in rhythm; 13. Patients whose known cancerous thrombus or deep vein thrombosis are stable for ≥2 weeks after receiving treatment with low molecular weight heparin (LMWH) or analogues with similar efficacy can be enrolled; 14. Any important abnormality in rhythm 15. Presence of meningeal metastasis, spinal cord compression or active brain metastasis prior to the start of study treatment. 16. Known allergy to the active or inactive ingredient of Savolitinib or Osimertinib; 17. 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; 18. Having participated in other drug clinical trials and received the study drug within 3 weeks prior to the start of study treatment; 19. Known allergy to the active or inactive ingredient of Savolitinib or Osimertinib; 20. Previous history of interstitial lung diseases, drug-induced interstitial lung diseases, radiation pneumonitis requiring glucocorticoid therapy and any active interstitial lung diseases; 21. Pregnant and lactating women; 22. Any other disease, metabolic abnormality, physical examination abnormality or laboratory examination abnormality, certain disease or state, based on which there is a reason to suspect that the subject is not suitable for the study drug, or one condition that will affect intepretaton of the study results or put the subject at high risk. 23. History of cirrhosis of any etiology and clinical stage; or other severe liver disease or chronic disease with severe liver involvement.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| PFS | 17 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
| Measure | Time frame | Description |
|---|---|---|
| Safety and tolerability | 17 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 objective response rate of the tumor (ORR) | 17 months after the last patient enrolled | the incidence of confirmed complete response or partial response |
| The disease control rate (DCR) | 17 months after the last patient enrolled | the incidence of complete response, partial response and stable disease |
| Duration of Response (DoR) | 17 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) | 17 months after the last patient enrolled | the time from the date of randomization to the date of death (all causes) |
| PFS | 17 months after the last patient enrolled | PFS evaluated by the IRC and investigators in the MET-amplified set |
| Development of diagnostic technology | 17 months after the last patient enrolled | The residual samples may be used for development of MET Companion Diagnostics (CDx) |
Countries
China
Contacts
PRINCIPAL_INVESTIGATORYilong Wu, MD
Guangdong Provincial People's Hospital
Outcome results
None listed