Study of Larotinib in Unresectable Advanced or Recurrent Esophageal Cancer

Inclusion Criteria:

1. Age:18-75 years, male or female.

2. Histologically or cytologically confirmed squamous cell carcinoma of the esophagusor advanced/metastatic disease.

3. Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

4. Life expectancy of greater than 3 months.

5. Documented objective radiographic or clinical disease progression on two previouslines of standard therapy.

6. Can provide archival tumor tissue sample for biomarker analysis (such as EGFRoverexpression/expansion status), biopsies are required if tissue samples cannot beprovided

7. Confirmed by the central laboratory as EGFR high expression.

8. Evaluable disease based on Response Evaluation Criteria In Solid Tumors (RECIST) 1.1.

9. Ability to swallow drugs.

10. Adequate organ function.

11. Voluntarily join the study and sign informed consent ad has good compliance.

Exclusion Criteria:

1. Prior therapies with EGFR targeted drugs including EGFR antibodies.

2. Previously treated with Irinotecan and Tegafur.

3. Anthracycline, nitrosourea, and mitomycin within 6 weeks; traditional Chinesemedicine for anti-tumor within 2 weeks;immune anti-tumor therapy. within 8weeks;other anti-tumor therapies within 4 weeks before randomization.

4. Not recovered from adverse events due to a previously administered agent.

5. Have undergone major surgery within 4 weeks prior to randomization (not includingdiagnostic surgery) or expect major surgery during the study period.

6. Previously or currently participating in other clinical trials within 4 weeks beforerandomization (subjects who have entered the follow-up period are calculated basedon the last use of experimental drugs or devices).

7. Received a live vaccine within 28 days before randomization or plan to receive livevaccine after enrollment.

8. Received a strong inducer or inhibitor of CYP3A4 enzyme within 1 week or receivedSolivudine or its structurally similar drugs within 56 days prior to randomization.

9. Simultaneously receiving any other anti-tumor treatment.

10. Has a known additional malignancy previously within the last 5 years with theexception of basal cell carcinoma of the skin, squamous cell carcinoma of the skinor any other tumor that has been cured。

11. Central nervous system metastasis or uncontrolled central nervous system metastasiscurrently in need of treatment; or confirmed central nervous system metastasis, butnot stable for more than 4 weeks after anti-tumor therapy; spinal cord compression,cancerous meningitis, or meningitis.

12. Clinically obvious gastrointestinal abnormalities, which may affect the intake,transport or absorption of drugs.

13. Having active gastrointestinal ulcer, active gastrointestinal bleeding, andperforation;

14. Risk of major bleeding or esophageal fistula;

15. Previous or present with interstitial lung disease or immunotherapy-associatedpneumonia; currently suffering from drug-induced pneumonia, radiation pneumonitisrequiring steroid therapy, or clinically symptomatic active pneumonia, or othermoderate to severe lungs that seriously affect lung function disease

16. Active infection during the screening period (including but not limited to infectionrequiring intravenous drip therapy), or unexplained fever (> 38.5°C)within 2 weeksprior to randomization.

17. Has congenital or acquired immune deficiency (such as HIV infection).

18. Known active Hepatitis B or C.

19. Has any of the following diseases within the first 12 months of randomization:myocardial infarction, coronary artery bypass grafting or peripheral artery bypassgraft surgery, heart failure (NYHA III to IV), etc and unstable angina with 6months.

20. Has thrombosis or embolism occurred within the first 12 months of randomization,such as cerebrovascular accident (including transient ischemic attack), deep veinthrombosis, pulmonary embolism with heparin or other similar drugs.

21. QTc interval (QTcF) corrected by Fridericia method> 470 ms; history of congenitallong QT interval syndrome; any history of clinically significant ventriculararrhythmias (such as ventricular tachycardia, ventricular fibrillation) Ortorsion-type ventricular tachycardia); left ventricular ejection fraction (LVEF) <50%.

22. Allergies or contraindications to Z650 excipients (mannitol, sodium carboxymethylstarch, micronized silica gel, magnesium stearate, silicified microcrystallinecellulose), or to Irinotecan or Tegafur or its formulation ingredients.

23. Has uncontrolled pleural effusion, pericardial effusion, pelvic effusion, or ascitesrequiring repeated drainage.

24. Has a history of organ transplantation or a history of allogeneic bone marrowtransplantation.

25. Pregnant, breastfeeding, or expecting to conceive or father children within theprojected duration of the study, starting with the screening visit through 6 monthsafter the last dose of study medication.

26. Has other serious acute or chronic diseases and are not suitable for participatingin clinical trials judged by investigators.