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.
Single group
Becotatug Vedotin (MRG003)
DrugAnti-EGFR antibody-drug conjugate (ADC) composed of a recombinant humanized anti-EGFR monoclonal antibody conjugated to monomethyl auristatin E (MMAE) via a cleavable valine-citrulline linker. Administered at 2.3 mg/kg intravenously every 3 weeks for 3 cycles.
Pucotenlimab
DrugHumanized anti-PD-1 monoclonal antibody (IgG4) that blocks the interaction between PD-1 and its ligands PD-L1 and PD-L2. Administered at 200 mg intravenously every 3 weeks for 3 cycles.
Major Pathological Response (MPR) Rate
MPR is defined as the proportion of participants with ≤10% residual viable tumor cells in the resected primary tumor specimen following neoadjuvant therapy, as assessed by central pathology review.
Objective Response Rate (ORR)
Proportion of participants achieving complete response (CR) or partial response (PR) based on RECIST 1.1 criteria, assessed by imaging (MRI/CT) after completion of 3 cycles of neoadjuvant therapy.
Pathological Complete Response (pCR) Rate
Proportion of participants with no residual viable tumor cells in the resected primary tumor specimen and regional lymph nodes following neoadjuvant therapy, as assessed by central pathology review.
Pathological Partial Response (pPR) Rate
Proportion of participants with significant reduction of residual viable tumor cells in the resected primary tumor specimen following neoadjuvant therapy, but not meeting the criteria for MPR or pCR, as assessed by central pathology review.
Event-Free Survival (EFS)
Time from treatment initiation to the first occurrence of any of the following events: disease progression precluding surgery, local or distant recurrence, or death from any cause.
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Sun Yat-sen University
Lead sponsor
Lepu Biopharma Co., Ltd.
Collaborator
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