A Multicenter, Prospective, Phase II Study of TROP-2 ADC in Combination With Toripalimab for Resectable Locally Advanced Oral Squamous Cell Carcinoma

A Multicenter, Prospective, Phase II Study of TROP-2 ADC in Combination With Toripalimab for Resectable Locally Advanced Oral Squamous Cell Carcinoma

This study is a multicenter, prospective, single-arm Phase II clinical trial evaluating the efficacy and safety of neoadjuvant therapy with TROP-2 ADC in combination with toripalimab for resectable locally advanced oral squamous cell carcinoma, followed by curative surgery and postoperative adjuvant radiotherapy or chemoradiotherapy.

Inclusion Criteria:

1. Ages 18-75 (inclusive); no gender restrictions.

2. Histologically or cytologically confirmed locally advanced oral squamous cell carcinoma (AJCC 8th Edition stages III-IVA).

3. Resectable and having not previously received any antitumor therapy for oral squamous cell carcinoma.

4. At least one evaluable tumor lesion according to RECIST version 1.1.

5. A tumor tissue specimen must be provided or a tumor biopsy must be performed prior to receiving neoadjuvant therapy for Trop-2 and PD-L1 immunohistochemical testing.

6. ECOG performance status of 0-1.

7. Expected survival of 6 months or longer.

8. Good bone marrow and organ function:

   • Hematologic system (no blood transfusion or hematopoietic growth factor therapy within the past 14 days):

     (1) Absolute neutrophil count (ANC) ≥ 1.5 × 10⁹/L (2) Platelets (PLT) ≥ 100 × 10⁹/L (3) Hemoglobin (Hb) ≥ 9 g/L

   • Liver function

     (1) Total bilirubin (TBIL) ≤ 1.5 × ULN (2) Alanine aminotransferase (ALT) ≤ 3 × ULN (3) Aspartate aminotransferase (AST) ≤ 3×ULN

   • Renal function

     1. Creatinine (Cr) ≤ 1.5×ULN
     2. Creatinine clearance (Ccr) (to be calculated only when creatinine > 1.5×ULN) > 50 mL/min (calculated using the Cockcroft-Gault formula)

   • Coagulation function (applicable to patients not receiving anticoagulant therapy; for subjects receiving anticoagulant therapy, INR or APTT should be within the expected therapeutic range for the anticoagulant)

     1. Activated partial thromboplastin time (APTT) ≤ 1.5×ULN
     2. International Normalized Ratio (INR) ≤ 1.5×ULN

9. Eligible patients of reproductive potential (both men and women) must agree to use reliable contraception (such as hormonal, barrier, or abstinence methods) with their partners during the trial and for at least 6 months after the last dose of treatment; female patients of childbearing potential (as defined in Appendix 5) must have a negative blood or urine pregnancy test within 7 days prior to the first administration of the study drug.

10. Subjects must provide informed consent for this study prior to enrollment and voluntarily sign a written informed consent form.

Exclusion Criteria:

1. Presence of precancerous lesions such as oral leukoplakia, erythroplakia, or lichen planus.
2. History of head and neck radiation therapy.
3. History of allogeneic hematopoietic stem cell transplantation or organ transplantation.
4. Received other investigational drugs or treatments not yet approved for marketing within 4 weeks prior to the first administration of the study drug.
5. Underwent major organ surgery (excluding needle biopsies and tracheotomies) or sustained significant trauma within 4 weeks prior to the first administration of the study drug.
6. Received an attenuated live vaccine within 4 weeks prior to the first administration of the study drug.
7. Patients who have received, within 14 days prior to the first administration of the study drug, or who require long-term systemic administration of glucocorticoids (prednisone > 10 mg/day or an equivalent dose of a similar drug) or other immunosuppressants during the study; the following exceptions apply: treatment with topical, ophthalmic, intra-articular, intranasal, or inhaled glucocorticoids; and short-term use of glucocorticoids for prophylactic treatment (e.g., to prevent contrast medium allergy).
8. Patients with active autoimmune diseases or a history of such diseases with a risk of recurrence (e.g., systemic lupus erythematosus, rheumatoid arthritis, vasculitis, etc.), excluding patients with clinically stable autoimmune thyroid disease or type 1 diabetes.
9. A history of other malignancies within 5 years prior to the first administration of the study drug, excluding tumors with negligible risk of metastasis or death, such as cured cervical carcinoma in situ, non-melanoma skin cancer, localized prostate cancer, and ductal carcinoma in situ of the breast.
10. A history of immunodeficiency, including a positive HIV antibody test.
11. Active infection currently requiring intravenous antimicrobial therapy.
12. Active hepatitis B (HBsAg-positive and HBV-DNA > 500 IU/mL or the study site's lower limit of detection [only if the study site's lower limit of detection is higher than 500 IU/mL]), active hepatitis C (patients who are HCV-antibody-positive but have HCV-RNA < the study site's lower limit of detection are eligible for inclusion); patients receiving prophylactic antiviral therapy other than interferon are eligible for inclusion. For subjects who are HBsAg-positive but HBV-DNA-negative, prophylactic antiviral therapy other than interferon must be administered.
13. Patients currently suffering from interstitial lung disease (excluding radiation-induced pulmonary fibrosis not requiring steroid therapy) or from pulmonary comorbidities resulting in clinically significant pulmonary dysfunction.
14. Patients currently suffering from active inflammatory bowel disease (ulcerative colitis, Crohn's disease).
15. Patients with a history of severe cardiovascular or cerebrovascular disease, including but not limited to:

(1) Severe cardiac rhythm or conduction abnormalities, such as ventricular arrhythmias requiring clinical intervention or second- or third-degree atrioventricular block; (2) Acute coronary syndrome, congestive heart failure, aortic dissection, stroke, or other cardiovascular or cerebrovascular events of Grade 3 or higher occurring within 6 months prior to the first dose; (3) Heart failure classified as New York Heart Association (NYHA) Class II or higher, or a left ventricular ejection fraction (LVEF) < 50%, or other structural heart disease deemed high-risk by the investigator; (4) Clinically uncontrolled hypertension (systolic blood pressure ≥ 150 mmHg and/or diastolic blood pressure ≥ 95 mmHg despite treatment).

16. Known history of severe allergic reactions to macromolecular drugs. 17. Known alcohol or drug dependence. 18. Patients with psychiatric disorders or poor compliance. 19. Pregnant or breastfeeding women. 20. Patients with a history of other serious systemic diseases, or other reasons deemed by the investigator to make them unsuitable for participation in this clinical trial.