Efficacy and Safety of Penpulimab Combined With Anlotinib and Chemotherapy

Inclusion Criteria:

1. only those who meet all the following requirements can be enrolled in thistrial: 1. age 18-75 years old, both male and female;

2. according to gastroscope / ultrasonic gastroscope biopsy, the pathologysuggests esophageal cancer, and the clinical diagnosis is ct2n1-3m0 orct3n0-3m0 or ct4n0-3m0, and the TNM stage is stage ii-iva;

3. patients with non cervical esophageal cancer;

4. have not received previous systemic and local treatment for esophageal canceraccording to RECIST 1 1 criteria at least one measurable lesion was used forimaging evaluation of neoadjuvant therapy;

• 5.ecog PS: 0-1 point;

6. estimated survival ≥ 12 months;

7. the subject had no dysfunction of major organs, and the investigator assessedthat the thyroid, lung, bone marrow, liver, kidney and heart functions werebasically normal; 8. women of childbearing age must have taken reliablecontraceptive measures or had a pregnancy test (serum or urine) within 7 daysbefore enrollment, and the results are negative, and are willing to useappropriate methods of contraception during the test and - 8 weeks after thelast administration of test drugs. For men, they must agree to use appropriatemethods of contraception or have been surgically sterilized during the trialand 8 weeks after the last administration of the trial drug;

9. the subjects voluntarily joined the study, signed the informed consent, hadgood compliance, followed the planned schedule, actively cooperated withreturning to the hospital for regular clinical follow-up and necessarytreatment, and cooperated with regular blood and tissue sample acquisition.

Exclusion Criteria:

1. 5 years of other malignant tumors, except for cured cervical carcinoma in situ,non melanoma skin cancer and superficial bladder tumor [ta (non invasivetumor), tis (carcinoma in situ) and T1 (tumor infiltrating basement membrane)];

2. patients with ulcerative esophageal squamous cell carcinoma;

3. patients with esophageal fistula or tracheal fistula;

4. those who are sensitive to anlotinib, pembrolizumab, albumin paclitaxel oroxaliplatin and excipients;

5. have a history of immune deficiency, including HIV positive or suffering fromother acquired or congenital immune deficiency diseases, or have a history oforgan transplantation;

6. patients with any severe and / or uncontrolled disease, including:

1. Patients with unsatisfactory blood pressure control (systolic blood pressure ≥ 160 mm Hg or diastolic blood pressure ≥ 100 mmHg); 2) Myocardial ischemia ormyocardial infarction of grade I or above; 3) Arrhythmia (including QT interval ≥ 480 MS) and grade I cardiac insufficiency; 4) Diabetes mellitus with poorblood glucose control (fasting blood glucose (FBG) >10mmol/l) or high-doseglucocorticoid treatment; 5) Active or uncontrolled severe infection; 6)Decompensated liver disease, active hepatitis B (HBV-DNA ≥ 104copies/ml or 2000iu/ml) or hepatitis C (hepatitis C antibody and HCV RNA positive) were allabove the lower limit of the analysis method; 7) Hyperthyroidism andhypothyroidism; 8) Active tuberculosis.

7. unrelieved toxic reactions higher than CTCAE grade 1 due to any previoustreatment, excluding hair loss;

8. esophageal cancer patients with active bleeding within 2 months of the primarylesion;

9. patients whose tumors have invaded the important blood vessels or are judged bythe investigator to be very likely to invade the important blood vessels duringthe follow-up study and cause fatal massive hemorrhage;

10. patients with multiple factors affecting oral drugs (such as inability toswallow, chronic diarrhea, intestinal obstruction, etc.), but patients withdysphagia who can drink water, can take anlotinib after dissolving theparticles;

11. the urine routine indicates that the urine protein is ≥ + +, and the 24-hoururine protein quantitation is confirmed to be >1.0 g;

12. received major surgical treatment, incision biopsy or obvious traumatic injurywithin 28 days before grouping;

13. abnormal coagulation function: inr>1.5 or prothrombin time (PT) >uln+4 secondsor APTT >1.5uln), with bleeding tendency or undergoing thrombolytic oranticoagulant therapy; Within 4 weeks before grouping, patients with anybleeding or bleeding events ≥ CTCAE grade 3 had unhealed wounds, ulcers orfractures;

14. Those who have had arterial / venous thrombotic events within 6 months, such ascerebrovascular accident (including transient ischemic attack), deep veinthrombosis and pulmonary embolism;

15. pregnant or lactating women;

16. patients with distant metastasis;

17. patients with significant myelosuppression;

18. have a history of mental illness or abuse of psychotropic drugs;

19. Patients who have participated in clinical trials of other drugs within 4weeks;

20. according to the judgment of the investigator, patients with concomitantdiseases that seriously endanger the safety of patients or affect thecompletion of the study;

21. the investigator believes that it is not suitable for inclusion.