Sintilimab to Prevent High-risk Oral Premalignant Lesions Cancerization

A Phase II Open-label, Single Arm Study to Evaluate the Efficacy of Sintilimab(IBI 308) to Prevent High-risk Oral Premalignant Lesions Cancerization

This is a non-randomized, phase II, open-label study. The goal of this clinical research study is to investigate how well sintilimab works in preventing high-risk oral premalignant lesions cancerization.

this study is a non-randomized, phase II, open-label study. Phase II clinical trials test the safety and effectiveness of an investigational drug or combination of drugs to learn whether it works in preventing or treating a disease.

the purpose of this study is to evaluate the effectiveness of sintilimab in preventing the onset of oral cancer in patients with high-risk oral premalignant lesions, who had oral cancer at least once before.

Inclusion Criteria:

1. Age ≥ 18

2. Histological evidence of oral premalignant lesions (such as leukoplakia and/or erythroplakia). A history of invasive oral cancer or oral cancer in situ, which was histologically confirmed.

3. With at least on high-risk profiles: a. have LOH at 3p14 and/or 9p21; b. pathologically diagnosis with severe dysplasia; c. size of lesions >200mm².

4. Eastern Cooperative Oncology Group Performance Status (ECOG) performance scale: 0-1.

5. Adequate organ and bone marrow function:

   • CBC: absolute neutrophil count (ANC) ≥ 1.5 × 10^9 / L; platelet count (PLT) ≥ 100 × 10^9 / L; hemoglobin content (HGB) ≥ 9.0 g / dL.
   • Liver function: serum total bilirubin (TBIL) ≤ 1.5 × normal upper limit (ULN); alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN.
   • Renal function: serum creatinine (Cr) ≤ 1.5 × ULN.

6. Female subject of childbearing potential should have a negative urine or serum pregnancy test < 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.

7. Female subjects of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile or abstain from heterosexual activity for the course of study therapy through 120 days after the last dose of study medication. Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses > 1 year.

8. Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of the study therapy.

9. Voluntarily signed written informed consent form, willing and able to comply with scheduled visits and other requirements of the study.

Exclusion Criteria:

1. Should receive subsequent adjuvant therapy (such as radiotherapy, chemotherapy, immunotherapy)

2. Received major surgery (such as craniotomy, thoracotomy or laparotomy) within 4 weeks of the first dose of study drugs or open wound, ulcer or fracture.

3. Received any anti-tumor therapy (chemotherapy, targeted therapy, tumor immunotherapy or arterial embolization) or radiotherapy within 4 weeks of the first dose of study treatment.

4. Prior therapy with anti-PD-1,anti-PD-L1,anti-CTLA4 antibody.

5. Currently participating in interventional clinical research treatment, or receiving other research medications within 4 weeks prior to the first dose or used research equipment

6. Received any investigational agent within 4 weeks of the first dose of study treatment.

7. Received radiotherapy within 4 weeks of the first dose of study treatment. Received systemic treatment with high-dose corticosteroids (> 10 mg daily prednisone equivalent) or other immunosuppressive drugs within 4 weeks of first dose. Inhaled or topical steroids and adrenal replacement steroid are permitted in the absence of active autoimmune disease.

8. Received attenuated live vaccine within 4 weeks of the first dose of study medication or plan to receive live vaccine during the study period.

9. Subjects with active, known or suspected autoimmune disease such as interstitial pneumonia, uveitis, Crohn's disease, autoimmune thyroiditis. Subjects with cured childhood asthma, type I diabetes mellitus and hypothyroidism only requiring hormone replacement, or skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment.

10. Known history of allogeneic organ or allogeneic hemopoietic stem cell transplantation

11. Known allergic or hypersensitive to docetaxel, any monoclonal antibody or any other components used in their preparation.

12. Uncontrolled concomitant disease, including but not limited to :

    • Active or poorly controlled severe infection
    • Human Immunodeficiency Virus (HIV) infection (HIV antibody positive)
    • Known acute or chronic active hepatitis B (HBV DNA positive) infection or acute or chronic active hepatitis C (HCV antibody positive and HCV RNA positive) infection
    • Active tuberculosis
    • Symptomatic congestive heart failure (New York Heart Association grade III-IV) or symptomatic, poorly controlled arrhythmia
    • Uncontrolled hypertension (SBP ≥ 160mmHg or DBP ≥ 100mmHg)
    • Prior arterial thromboembolism event, including myocardial infarction, unstable angina, stroke, and transient ischemic attack, within 6 months of enrollment

13. Known history of, or any evidence of active, non-infectious pneumonitis.

14. Other primary malignancy, with the exception of the skin or squamous cell carcinoma of the skin or in situ cervical cancer.

15. Women who are pregnant or lactating