This is a phase 2, open-label, single-arm clinical trial evaluating neoadjuvant therapy with Becotatug vedotin (MRG003) combined with Pucotenlimab (HX008) in patients with previously untreated, resectable stage III-IVA oral cavity squamous cell carcinoma (OSCC) with a PD-L1 Combined Positive Score (CPS) of 1 or higher.
Eligible participants will receive 3 cycles of neoadjuvant treatment (Becotatug vedotin 2.3 mg/kg plus Pucotenlimab 200 mg, intravenously, every 3 weeks), followed by radical surgery 2-3 weeks after the last cycle of neoadjuvant therapy. Postoperative adjuvant radiotherapy will be stratified based on pathological response and risk factors: patients achieving major pathological response (MPR, defined as ≤10% residual viable tumor) with negative margins and no extranodal extension (ENE) will receive de-escalated radiotherapy (50-54 Gy); patients not achieving MPR or with high-risk features will receive standard radiotherapy (60-66 Gy) with or without concurrent cisplatin chemotherapy.
The primary endpoint is major pathological response (MPR). Secondary endpoints include objective response rate (ORR), pathological complete response (pCR), event-free survival (EFS), overall survival (OS), and safety profile. Exploratory biomarkers will be assessed in tumor tissue and peripheral blood.
A total of 32-33 participants will be enrolled using a Simon two-stage optimal design (α=0.05, power=80%).
Voluntary participation with written informed consent, good compliance, and willingness to complete follow-up.
Age ≥18 years and ≤70 years, regardless of gender.
ECOG performance status score of 0 or 1.
Histopathologically confirmed, previously untreated, primary oral cavity squamous cell carcinoma (OSCC); central laboratory-confirmed PD-L1 Combined Positive Score (CPS) ≥1; clinical stage III-IVA (AJCC 8th edition) with potential for curative surgical resection as assessed by the investigator; no evidence of definite locoregional residual or distant metastasis.
Age >70 years or <18 years.
History of other malignancies within the past 5 years, except adequately treated basal cell carcinoma, squamous cell carcinoma of the skin, or carcinoma in situ of the cervix.
HIV infection.
HBsAg positive with HBV DNA >200 IU/mL or 1000 copies/mL.
Sun Yat-sen University
Lead sponsor
Lepu Biopharma Co., Ltd.
Collaborator