Tislelizumab Combined With Anlotinib as Second-line Therapy in Thymoma and Thymic Carcinoma

Tislelizumab Combined With Anlotinib as Second-line Therapy in Thymoma and Thymic Carcinoma: An Open-label, Single-centre, Phase 2 Study

It is an open-lable, single-arm, single-center, phase II clinical trial conducted in China, and plan to recruiting 20 patients who were progressed after first line chemotherapy or chemotherapy combined with immunotherapy. The purpose of this study is to evaluate the safety and efficacy of tislelizumab combined with anlotinib as second-line in thymoma and thymic carcinoma.

Inclusion Criteria:

1. Age 18-75 years old, gender is not limited.

2. Histologically or cytologically confirmed thymoma or thymic carcinoma.

3. Disease progression during or after first-line chemotherapy (with or without immunotherapy).

4. At least one measurable solid tumor lesion according to RECIST 1.1 criteria.

5. Estimated survival ≥ 3 months; United States Eastern Cooperative Oncology Group (ECOG) score: 0 or 1 point.

6. Vital organ function meets the following criteria:

   1. Hematological examination (no use of any blood components and cell growth factors within 14 days prior to initiation of study treatment): i. neutrophil count (ANC) ≥ 1.5×109/L; ii. platelet count (PLT) ≥100 × 109/L; iii. hemoglobin (Hb) ≥80g/L;
   2. total bilirubin (TBIL) ≤ 1.5× upper limit of normal (ULN), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5× ULN, serum albumin (ALB) ≥28g/L;
   3. left ventricular ejection fraction (LVEF) ≥50%;

7. Female subjects of childbearing potential must have a serum pregnancy test within 7 days prior to the first dose with a negative result; and must be non-lactating; Female subjects of childbearing potential and male subjects whose partners are women of childbearing potential must agree to comply with contraceptive requirements from the time of signing the informed consent form until 8 weeks after the end of the last treatment session.

8. Informed consent was signed.

Exclusion Criteria:

1. Prior treatment with anlotinib or any other anti-angiogenesis drugs.

2. Patients with symptomatic brain metastasis.

3. Other primary malignancy in the past 5 years, with the exception of: (radical Non-melanoma skin cancer or cured cervical in-situ carcinoma).

4. Subjects with active, known or suspected autoimmune disease such as interstitial pneumonia, uveitis, Crohn's disease, autoimmune thyroiditis.

5. Severe infections within 4 weeks prior to inclusion.

6. Any of the following severe acute comorbidities prior to inclusion:

   1. Does not have uncontrolled pleural effusion/pericardial effusion/or ascites as determined by the investigator;
   2. Unstable angina myocardial infarction or uncontrolled congestive heart failure within 12 months;
   3. Uncontrollable hypertension;
   4. Urine routine test protein ≥++, and confirmed 24 hours urine protein> 1.0 g;

7. Imaging shows that the tumor has invaded a vital vessel perimeter or who, in the opinion of the investigator, have a high likelihood of fatal hemorrhage due to tumor invasion of a vital vessel during the follow-up study;

8. Clinically significant hemoptysis (daily hemoptysis greater than 50ml) within 3 months prior to enrollment; or significant clinically significant bleeding symptoms or defined bleeding tendency, such as gastrointestinal bleeding, hemorrhagic gastric ulcer, baseline fecal occult blood ++ and above, or suffering from vasculitis;

9. Major surgical treatment, incisional biopsy, or significant traumatic injury within 28 days prior to inclusion.

10. Presence of any mental disease or drug abuse disorder that may interfere with subject's ability for being compliant with study requirements.

11. Known hypersensitivity or allergy to monoclonal antibody.

12. Is receiving systemic steroid therapy < 2 weeks prior to the first dose of trial treatment or receiving any other form of immunosuppressive medication.

13. Diagnosis of immunodeficiency or undergoing systemic glucocorticoid therapy or any other immunosuppressive therapy that was continued within 2 weeks prior to the first dose.

14. Participation in another clinical trial within 28 days.

15. Any condition that, in the opinion of the investigator, would interfere with evaluation or interpretation of patient safety or study results.