A Study of HA121-28 Tablets in Patients With Medullary Thyroid Carcinoma (MTC)

Inclusion Criteria:

1. Be willing to participate in the clinical trial and sign the informed consent;
2. Men and women aged ≥18 years;
3. Histologically confirmed unresectable locally advanced or metastatic MTC with at leastone measurable lesion per RECIST1.1;
4. Evidence of disease progression within 12 months prior to signing informed consent;
5. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0~1;
6. Laboratory test results must meet the following criteria: Absolute neutrophil count (ANC) ≥1.5 x 10^9/L; Platelet count (PLT) ≥75×10^9/L; Hemoglobin (Hb) ≥90 g/L; Alanineaminotransferase (ALT) and aspartate aminotransferase (AST) ≤3 x upper limit of normal (ULN) (in patients with liver metastasis ≤5.0 x ULN); Total bilirubin ≤ 1.5 x ULN;Serum creatinine≤ 1.5 x ULN；Prothrombin time (PT) and activated Partial ThromboplastinTime (APTT) ≤ 1.5 x ULN；
7. Left ventricular ejection fraction (LVEF)≥50% in echocardiogram；
8. Male and female subjects of childbearing potential must agree to take effectivecontraception during the treatment period and for 6 months after the last dose ofstudy medication;
9. Female participants must have negative results of serum/urine pregnancy test within 7days prior to enrollment and must not be breastfeeding.

Exclusion Criteria:

1. Previous treatment with selective RET inhibitor, such as blu-667, loxo-292, etc.;
2. Patients who had participated in other clinical trials and received the treatmentwithin 4 weeks prior to enrollment;
3. Systemic anti-tumor treatment such as small molecule targeted drugs, cytotoxic drugs,immunotherapy and radiotherapy within 4 weeks of the first dose of the study drug, orlocal palliative radiotherapy for pain relief within 2 weeks;;
4. Patients who cannot swallow or have chronic diarrhea (except for those induced by MTC)and intestinal obstruction, or other factors which may affect the administration andabsorption of the study drug;
5. History of other malignancies within the past 5 years or currently suffering fromother malignancies, except for cured cervical carcinoma in situ, non-melanoma skincancer, and superficial bladder tumor;
6. Patients who meet one of the following criteria: 1) Corrected QT (QTc) ≥450 ms (corrected using Fridericia's formula (QTcF): QTcF = QT/(RR^0.33)); 2) Any clinicallysignificant abnormalities of rhythm, conduction or morphology in the restingelectrocardiogram (ECG) requiring therapeutic intervention;
7. Urine protein≥2+ and urine protein > 1.0 g/24h;
8. Known severe concomitant and/or uncontrolled diseases, including but not limited to: 1)Uncontrolled hypertension (systolic pressure ≥150 mmHg or diastolic pressure ≥100mmHg, after treatment); 2)Significant cardiovascular and cerebrovascular events,arterial or venous fistulae thrombotic events, myocardial infarction, congestive heartfailure (NYHA classification ≥2) or severe ventricular arrhythmia within 6 months ofthe first dose of the study drug; 3) Liver cirrhosis, decompensated liver disease; 4)Renal failure required hemodialysis or peritoneal dialysis; 5) History of humanimmunodeficiency, including HIV positive, or other acquired/congenital immunedeficiency diseases, or history of organ or bone marrow transplantation; 6)Uncontrolled pericardial effusion, pleural effusion or ascites;7） interstitialpneumonia required steroid therapy or severe infection required systemic treatment,which is judged not suitable for the study by the investigator;
9. Patients with spinal cord, meningeal and brain metastases (except for stablesymptomatic or asymptomatic brain metastases);
10. Ongoing adverse events>grade 1 due to any previous treatment at the time of enrollment (except for hair loss and pigmentation);
11. Patients who have undergone major surgery or have not recovered from invasiveoperation within 4 weeks prior to initiation of study treatment;
12. Patients with bleeding diathesis (such as active peptic ulcer) or treated withanticoagulants or vitamin K antagonists, such as warfarin, heparin or their analogues;
13. Known active Hepatitis B or Hepatitis C virus infection: HBsAg positive with HBV DNAhigher than the lower limit of detection range of the site, or HCV antibody positivewith HCV RNA higher than the lower limit of detection range of the site);
14. Patients with known history of neurological or psychiatric disorders, includingepilepsy or dementia;
15. Not suitable for the study assessed by the investigators.