Ivonescimab Combined with Chemotherapy As First-line Treatment of Relapsed or Metastatic Thymic Cancer: a Prospective, Single Arm, Phase II Trial

Inclusion Criteria:

1. Untreated metastatic or recurrent inoperable thymic cancer patients at the initialstage; All patients need to undergo baseline PET/CT (or neck, chest, upper abdominalCT+cranial MR) for clinical staging.

2. The patient's age is ≥ 18 years old, with no gender restrictions.

3. Pathological diagnosis of thymic carcinoma through cytology/histology.

4. Expected survival period ≥ 3 months.

5. ECOG (Performance Status, PS) score is 0-1 points.

6. Organ function meets: Hematology: I. neutrophils ≥ 1500109/L;II. Platelet ≥ 100109/L; iii、 Hemoglobin >90g/L; Renal function: I. serum creatinine ≤ 1.5ULN or creatinine clearance rate (CrCl) ≥ 50mL/min; II. Urinary protein < 2+ or 24h urinary protein quantitation < 1.0g; Liver function: I, AST or ALT ≤ 3ULN; For patients with liver metastasis, itcan be ≤ 5ULN; ii. Total bilirubin ≤ 1.5ULN, liver metastasis patients can be ≤ 3ULN; Iii: serum albumin (ALB) ≥ 28g/L. Coagulation function: NR or APTT ≤ 1.5ULN. Cardiac function: left ejection fraction (levf) ≥ 50%. Thyroid function: thyroid stimulating hormone (TSH), free thyroxine (FT4), or free triple Iodothyronine (FT3) was within ± 10% of normal values.

7. There were measurable lesions (according to irecist criteria).

8. Subjects must understand and voluntarily sign an informed Consent form, andvoluntarily comply with other requirements of the study.

9. Female subjects with reproductive function must have urine or serum within 3 daysbefore the first medication Pregnancy test (if the urine pregnancy test resultcannot be confirmed as negative, serum pregnancy test is required Check, the serumpregnancy results shall prevail). If a female with fertility is different from amale without sterilization The partner had sex, and the subject agreed to continueto use contraception and avoid breastfeeding during the medication period Milk.

10. The male subject agreed to continue using contraceptive methods during themedication period.

Exclusion Criteria:

1. Patients with thymoma component suspected by pathological diagnosis (only thymiccancer patients were enrolled).

2. The patient has or is suspected of having autoimmune disease. Note: Patients withvitiligo, type I diabetes, or Hashimoto's thyroiditis who have hypothyroidism butonly need hormone replacement therapy can be included in the study when there is noobvious sign of recurrence.

3. Patients need to receive systemic cortisol treatment (>10mg prednisolone [orequivalent dose] / day) or use other immunosuppressive drugs within 14 days afterenrollment. Note: inhaled or topical corticosteroids, or adrenal hormone replacementtherapy (>10mg prednisolone [or equivalent dose] / day) can be accepted for patientswithout obvious autoimmune disease.

4. Patients with grade 3-4 interstitial lung disease.

5. At the same time, the patient has other malignant tumors and need anti-tumortreatment.

6. Patients with other malignant tumors in the past (excluding skin malignant tumorsother than non melanoma, and carcinoma in situ in the following parts [bladder,stomach, colorectal, endometrial, cervical, melanoma or breast]) cannot be includedin this study. However, if the malignant tumor has achieved complete remission forfive years or more and does not need to receive additional anti-tumor treatmentduring this study, it can be included in the study.

7. Received live attenuated vaccine within 4 weeks before the first dose or plannedduring the study.

8. Major surgical operations (craniotomy, thoracotomy or laparotomy) or unhealedwounds, ulcers or fractures within 4 weeks before the first administration.

9. The investigator believes that the patient is medically, psychologically, orphysiologically unable to complete the study or understand the information in thepatient manual.

10. Previously received anti-PD-1, anti-PD-L1, anti-CTLA4, other drugs targeting T cellcostimulation or immune regulatory pathways, and anti vascular drugs.

11. Myocardial infarction and poorly controlled arrhythmia occurred within 6 monthsbefore the first administration (including QTc interval ≥ 450 ms for males and ≥ 470ms for females) (QTc interval was calculated according to fridericia formula); Oraccording to NYHA criteria for grade III-IV cardiac insufficiency or leftventricular ejection fraction <50% by cardiac color Doppler ultrasound.

12. The subject had grade ≥ 2 CTCAE peripheral neuropathy.

13. Uncontrolled pleural effusion, pericardial effusion or ascites requiring repeateddrainage. Only a small amount of pleural fluid, ascites and pericardial effusionwithout clinical symptoms revealed by imaging can be enrolled.

14. There are active patients with hepatitis B, C, tuberculosis, syphilis or otherserious infections with poor clinical control.

15. HIV test positive or have been diagnosed with acquired immune deficiency disease (AIDS).

16. Allergic to the study drug or known history of severe allergy to any monoclonalantibody (NCI-CTCAE 5.0 grade > 3).

17. Those who received live or attenuated vaccines within 28 days before the first doseor had plans to receive such vaccines during the study; However, inactivated viralvaccines for seasonal influenza are permitted.

18. Have a history of severe bleeding tendency or coagulation dysfunction. Those who haddeep vein thrombosis, were using anticoagulant or platelet therapy, or had deep veinthrombosis or serious bleeding caused by the use of antiangiogenic drugs in the past 3 months before enrollment; Or any other history of severe thromboembolism (implantable venous port or catheter-derived thrombosis, or superficial venousthrombosis is not considered "severe" thromboembolism).

19. Vascular events occurred in the past 6 months, including cerebrovascular accidents (including transient ischemic attack), any arterial thromboembolic events, includingmyocardial infarction, pulmonary embolism, unstable angina pectoris, etc.

20. A history of hereditary bleeding prone disease or coagulation dysfunction is known.

21. Poorly controlled blood pressure (defined as blood pressure ≥ 160/100mmHg under theoptimal treatment of hypertension).

22. Pregnant or lactating women.

23. Have a history of alcohol or drug abuse.