Phase II Trial of Tunlametinib in NRAS-Mutant Advanced Thyroid Cancer

Inclusion Criteria: 1. Patients voluntarily join this study and sign an informed consent form; 2. Age: ≥ 18 years old, male or female not limited; 3. For locally advanced or recurrent/metastatic thyroid cancer diagnosed by histology and unable to undergo curative surgery, one of the following requirements must be met: 1. Iodine refractory thyroid cancer; 2. Differentiated thyroid cancer not suitable for iodine therapy; 3. High grade, poorly differentiated or poorly differentiated thyroid cancer; 4. Undifferentiated thyroid carcinoma; 4. Have undergone NGS testing (at our hospital or an external hospital), and be able to find that the test report or medical history has recorded a positive result for NRAS mutation in the gene test. 5. ECOG score 0-2 points; According to RECIST v1.1 evaluation, there is at least one assessable lesion; 7\. Expected survival\>12 weeks; 8. The main organ function and bone marrow function are normal. * Blood routine: Hemoglobin ≥ 90 g/L (no blood transfusion within 14 days); Absolute neutrophil count ≥ 1.5 × 109/L; platelet count ≥ 100 × 109/L; * Liver function: Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) are ≤ 2.5 times the upper limit of normal (ULN). If there is liver metastasis, ALT and AST are ≤ 5 times ULN, and ALP is ≤ 6 times ULN; Total bilirubin ≤ 1.5 × ULN; Albumin ≥ 30 g/L; * Renal function: serum creatinine ≤ 1.5 × ULN or creatinine clearance rate calculated by Cockroft Gault formula\>60 mL/min; * Cardiac function: Echocardiography shows a left ventricular ejection fraction (LVEF) of ≥ 55%; ECG QTcF ≤ 480ms; Creatine kinase (CK) ≤ 1 × ULN, troponin/hypersensitive troponin ≤ 1 × ULN; * Coagulation function: International normalized ratio of prothrombin time (INR) ≤ 1.5 × ULN; Activated partial thromboplastin time (APTT) ≤ 1.5 × ULN; 9. Women of childbearing age must undergo a pregnancy test (serum or urine) with a negative result within 14 days before enrollment, and voluntarily use appropriate contraception methods during the observation period and within 3 months after the last administration of the study drug; For males, surgical sterilization or consent to use appropriate contraception methods during the observation period and within 3 months after the last administration of the study drug should be used. Exclusion Criteria: 1. Within 4 weeks before the first medication, major surgery (excluding biopsy and outpatient minor surgery, such as placement of vascular access) or severe trauma occurred; 2. There are clinical symptoms of third interstitial fluid accumulation that cannot be controlled by drainage or other methods (such as a large amount of pleural fluid or ascites); 3. Cardiovascular and cerebrovascular diseases with impaired heart function or significant clinical significance, including but not limited to any of the following: Within 6 months prior to the start of treatment, acute coronary syndrome occurred, including acute myocardial infarction, unstable angina, coronary artery bypass grafting, coronary angioplasty, and stent implantation; * Symptomatic congestive heart failure (NYHA classification ≥ II); Evidence of clinically significant arrhythmia and/or conduction abnormalities within 6 months prior to the start of treatment or at present; * Poor control of hypertension (systolic blood pressure ≥ 140 and/or diastolic blood pressure ≥ 90 mmHg under medication control); Abnormal cardiac valve morphology (≥ grade 2) recorded by echocardiography, Note: Patients with grade 1 abnormal valve morphology (such as mild regurgitation/stenosis) are allowed to be enrolled, but patients with moderate valve thickening are prohibited from being enrolled; * History of congenital long QT syndrome; Or those who take drugs known to prolong the QT interval and cannot guarantee discontinuation during the study period; 4. Previous or screening retinal diseases, such as retinal vein occlusion (RVO), retinal artery occlusion, retinal vasculitis, diabetes retinopathy, hypertensive retinopathy, retinal telangiectasia (Costs disease), retinal pigment epithelial detachment (RPED), etc; Risk factors for RVO during screening (such as uncontrolled glaucoma or high intraocular pressure, history of high viscosity or hypercoagulability syndrome); Retinal diseases such as RPED; 5. Patients with interstitial lung disease or interstitial pneumonia, including clinically significant radiation pneumonitis (i.e. affecting daily living activities or requiring intervention treatment); 6. Positive for human immunodeficiency virus (HIV) antibodies, syphilis antibodies (Anti TP), hepatitis C virus (HCV) antibodies and HCV RNA, hepatitis B virus surface antigen (HBsAg) and HBV DNA (HBsAg positivity requires further testing for HBV DNA, HBV DNA ≥ 200 IU/ml, or ≥ 103 copies/ml); 7. History of allogeneic bone marrow transplantation or organ transplantation; 8. There are uncontrollable active infectious diseases (such as intravenous drip of antibiotics, antifungal or antiviral drugs) within 2 weeks before the first administration, or fever of unknown cause\>38.5 ° C occurs during screening/before the first administration; 9. Irreversible electrolyte abnormalities (hypokalemia, hypomagnesemia, hypocalcemia detected by blood biochemistry); 10. Neuromuscular diseases related to CK elevation in the past or present (such as inflammatory myopathy, muscular dystrophy, amyotrophic lateral sclerosis, spinal muscular atrophy, rhabdomyolysis syndrome); 11. Arterial/venous thrombotic events that occur within 6 months prior to the first use of medication, such as cerebrovascular accidents (including temporary ischemic attacks, cerebral hemorrhage, cerebral infarction), deep vein thrombosis, and pulmonary embolism; 12. Within 4 weeks prior to the first use of medication, the occurrence of Grade 3 bleeding symptoms as defined in the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI CTCAE