cancer
Conditions
Interventions
Interventional group:Sunvozertinib combined with chemotherapy(Pemetrexed +platinum)
Sponsors
West China Hospital,Sichuan University
Eligibility
Sex/Gender
All
Age
18 Years to 80 Years
Inclusion criteria
Inclusion criteria: 1. Research participants must understand the requirements and content of clinical trials, and provide a handwritten signed and dated informed consent form before clinical trials, sample collection, and analysis. 2. 18 years old = age = 80 years old. 3. Histopathology or cytology confirms and records local progression (American Joint Committee on Cancer, AJCC 8th edition stage IIIB and IIIC) or metastasis (stage IV) non-squamous non-small cell lung cancer. 4. EGFR sensitive mutations confirmed by accredited local laboratories, including exon 19 deletion, exon 21 L858R mutation, and exon 20 T790M mutation. 5. There is no disease progression within the past two weeks after signing the informed consent form and the score is 0 – 1 according to the Eastern Cooperative Oncology Group (ECOG) standard, and the predicted survival time is = 12 weeks. 6. Study participants need to progress after EGFR-TKI targeted therapy or be intolerant to standard treatment; if they carry T790M mutation, they need to be treated with osimertinib or other third-generation EGFR TKI. 7. Have not received systemic chemotherapy for locally advanced or metastatic disease in the past. 8. Sufficient bone marrow hematopoiesis or other organ reserves • Hematology: ? Absolute neutrophil count (ANC) = 1.5 × 109/L ? Platelets = 100 × 109/L ? Hemoglobin = 9 g/dL • Liver: ? Total bilirubin = 1.5 × upper limit of normal (ULN); study participants with Gilbert syndrome (unconjugated hyperbilirubinemia) or liver metastases, total bilirubin = 3 × ULN ? If there is no liver metastasis, alanine aminotransferase (ALT) = 2.5 × ULN and aspartate aminotransferase (AST) = 2.5 × ULN; or if liver metastasis is present, ALT and AST = 5 × ULN • Kidney: Creatinine = 1.5 × ULN and creatinine clearance calculated or measured by the Cockcroft-Gault method = 60 mL/min • Coagulation: ? International Normalized Ratio (INR) = 1.5 × ULN ? Partial thromboplastin time (APTT) = 1.5 × ULN • other: ? Serum amylase = 1.5 × ULN, and serum lipase = 1.5 × ULN 9. There is a measurable lesion according to RECIST 1.1: there is at least one lesion with a long diameter =10 mm (node ??lesions need a short diameter =15 mm) without radiotherapy, and the baseline can be accurately measured under CT or MRI and Lesions that can be measured repeatedly. If the study participant only has lesions after radiotherapy, and the lesions have been clearly shown to have radiographic progression and can be measured, they can be selected as target lesions. 10. Research participants with brain metastases can be included in this study if they meet the following conditions: asymptomatic or stable after local treatment (such as WBRT or SRS); no need for steroid treatment; long-term completion of local treatment At least four weeks before adverse effects return to baseline. 11. Male research participants who have a female partner and intend to have children should use barrier contraception (such as condoms) during their participation in the clinical trial study and within 6 months after the last dose. Male study participants cannot donate sperm while participating in the clinical trial and for 6 months after the last dose. If male research participants wish to have children, it is recommended that sperm be frozen before starting the clinical trial. 12. Female research participants should take contraceptive measures from the time of screening to 6 weeks after the last dose, cannot breastfeed, and have a negative pregnancy test (blood or urin
Exclusion criteria
Exclusion criteria: 1. Research participants who have received the following treatments must be excluded: • Have been treated with an EGFR-targeted drug within 4 weeks before the first dose of study drug. • Received any cytotoxic chemotherapy or other anti-neoplastic drug treatment within 2 weeks before the first dose of study drug. • Received radiation therapy within 4 weeks before the first dose or have not yet recovered from radiation therapy-related toxicity to =Grade 1 or baseline. Stereotactic radiosurgery and stereotactic body radiation therapy (except for intracranial lesions) can be received 14 days before the first dose. • Are receiving (or unable to stop taking) medications or herbal supplements that may be strong CYP3A inhibitors (1 week) or inducers (2 weeks) within 1 – 2 weeks before the first dose of suvotinib. • Study participants who have undergone major surgery other than diagnosis or biopsy within 4 weeks before the first dose, or who are expected to undergo major surgery during the study period. • Other drugs under development must be discontinued for more than 5 half-lives and negotiated with the investigators before they can be included in the study. 2. There is spinal cord compression or meningeal metastasis. 3. Have a history of malignant tumors within 2 years (except for basal cell carcinoma of the skin or cervical cancer in situ that has been fully treated). 4. It is known that there is a clear resistance mechanism after EGFR-TKI targeted therapy, and there are accessible treatments for this. 5. Before the first dose, there are CTCAE > grade 1 adverse events (any degree of alopecia, except grade 2 neuropathy related to previous platinum therapy) caused by previous treatment (such as adjuvant chemotherapy, radiotherapy, etc.). 6. Have a history of stroke or intracranial hemorrhage within 6 months before the first dose. 7. According to the investigator's judgment, there is any serious or poorly controlled systemic disease, including poorly controlled hypertension and active bleeding (such as hemophilia, von Willebrand's disease). 8. Research participants with persistent or active infections, including but not limited to hepatitis B (HBV), hepatitis C (HCV), human immunodeficiency virus (HIV) and COVID-19 infection (with clinical symptoms, signs, etc. as judged by the researcher) researcher. Local clinical practices will be referenced for COVID-19 testing. 9. Any of the following heart-related diseases or abnormalities: Resting ECG shows calibrated QTc interval (QTcF) > 470 msec Resting ECG showing any serious abnormality in heart rate rhythm, conduction or pattern, such as complete left bundle branch block, third degree heart block, second degree heart block, PR interval > 250 msec Any factor that can cause QTcF prolongation or arrhythmia, such as heart failure, hypokalemia, congenital QT prolongation syndrome, family history of QT prolongation syndrome or other sudden death diseases under 40 years of age, or other diseases known to cause QT Interval prolonging diseases Suffering from atrial fibrillation (unless it is caused by drugs and has returned to normal after stopping the drug). Myocardial infarction, New York Heart Association grade 2 congestive heart failure, and arrhythmias poorly controlled by drugs within = 6 months before the first dose 10. Past history of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis requiring steroid treatment, or any interstitial lung disease with active cli
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Objective Response Rate (ORR) ; | — |
Secondary
| Measure | Time frame |
|---|---|
| Duration of Response (DoR) ;Progression-free survival (PFS);Overall survival (OS);Number of participants with adverse events (AEs) according to CTCAE 5.0 ; | — |
Countries
China
Contacts
Public ContactLu You
West China Hospital,Sichuan University
Outcome results
None listed