Neoadjuvant Presurgical Becotatug Vedotin (MRG003) Plus Pucotenlimab (HX008) in Oral Cavity Squamous Cell Carcinoma

NCT07766889 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: SL-B2026-374-02
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 2

Brief Summary

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%).

Conditions

Oral Squamous Cell Carcinoma; Head and Neck Cancer; Locally Advanced Head and Neck Cancer; Neoadjuvant Therapy

Keywords

MRG003, Becotatug vedotin, Pucotenlimab, anti-PD-1, ADC, EGFR, neoadjuvant therapy, oral squamous cell carcinoma, OSCC, head and neck cancer

Outcome Measures

Primary Outcomes (1)

• 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.

  At the time of surgery, following 3 cycles of neoadjuvant therapy (each cycle is 21 days)

Secondary Outcomes (13)

• Objective Response Rate (ORR)

  At the end of Cycle 3 (each cycle is 21 days), prior to surgery

• Pathological Complete Response (pCR) Rate

  At the time of surgery, following 3 cycles of neoadjuvant therapy (each cycle is 21 days)

• Pathological Partial Response (pPR) Rate

  At the time of surgery, following 3 cycles of neoadjuvant therapy (each cycle is 21 days)

• Event-Free Survival (EFS)

  Up to 5 years

• Overall Survival (OS)

  Up to 5 years

Study Arms (1)

Neoadjuvant MRG003 + Pucotenlimab

EXPERIMENTAL

Participants receive 3 cycles of neoadjuvant Becotatug vedotin (MRG003) 2.3 mg/kg plus Pucotenlimab (HX008) 200 mg intravenously every 3 weeks, followed by radical surgery 2-3 weeks after the last neoadjuvant cycle. Postoperative adjuvant radiotherapy is stratified based on pathological response and risk factors.

Drug: Becotatug Vedotin (MRG003); Drug: Pucotenlimab

Interventions

Becotatug Vedotin (MRG003) DRUG

Anti-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.

Also known as: MRG003

Neoadjuvant MRG003 + Pucotenlimab

Pucotenlimab DRUG

Humanized 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.

Also known as: HX008

Neoadjuvant MRG003 + Pucotenlimab

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Adequate organ function within 14 days prior to the first dose, without transfusion or hematopoietic growth factor support:
• Bone marrow: ANC ≥1.5×10\^9/L; platelet count ≥100×10\^9/L; hemoglobin ≥90 g/L.
• Liver: TBIL ≤1.5×ULN; AST/ALT ≤3.0×ULN; ALP ≤2.5×ULN; serum albumin ≥28 g/L.
• Kidney: creatinine clearance (Ccr) ≥40 mL/min (calculated by Cockcroft-Gault formula) or serum creatinine ≤1.5×ULN.
• Coagulation: INR ≤1.5×ULN and APTT ≤1.5×ULN (excluding patients receiving therapeutic anticoagulation).
• Cardiac: LVEF ≥50% with no significant cardiac dysfunction.
• Negative serum pregnancy test within 7 days prior to the first dose for women of childbearing potential; all fertile male and female participants must agree to use highly effective contraception from signing of informed consent through 1 year after the last dose of Pucotenlimab.

You may not qualify if:

• 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.
• HCV antibody positive.
• Severe concurrent diseases that may pose significant risks or affect trial compliance, including unstable cardiac disease, renal disease, chronic hepatitis, poorly controlled diabetes (fasting blood glucose \>1.5×ULN), severe cognitive impairment, or psychiatric disorders.
• Active pulmonary tuberculosis infection within the past 1 year, or history of active tuberculosis \>1 year ago unless documented prior standard anti-tuberculosis treatment.
• History of interstitial lung disease.
• Active, known, or suspected autoimmune disease. Exceptions: type I diabetes, hypothyroidism requiring only hormone replacement therapy, and skin conditions not requiring systemic treatment (e.g., vitiligo, psoriasis, alopecia).
• Systemic corticosteroids (\>10 mg/day prednisone equivalent) or other immunosuppressive therapy within 28 days prior to signing informed consent. Patients receiving ≤10 mg/day prednisone equivalent or inhaled/topical corticosteroids are eligible.
• Live vaccination within 30 days prior to signing informed consent or planned during the study.
• Prior surgery, chemotherapy, radiotherapy, immunotherapy, or other anti-tumor therapy for head and neck cancer (excluding diagnostic procedures).
• Known hypersensitivity to macromolecular protein preparations, or any component of Becotatug vedotin, Pucotenlimab, or cisplatin.
• Pregnancy, lactation, or anticipated pregnancy during the study period.

Sponsors & Collaborators

• Sun Yat-sen University: lead
• Lepu Biopharma Co., Ltd.: collaborator

Study Sites (2)

Hospital of Stomatology, Sun Yat-sen University

Guangzhou, Guangdong, 510055, China

Location

Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, 510060, China

Location

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck; Head and Neck Neoplasms

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site

Central Study Contacts

Yanping Mao

CONTACT

+86-13500019575; maoyp5@mail.sysu.edu.cn

Yanfeng Chen

CONTACT

chyanf@mail.sysu.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Mao Yanping, Professor, Department of Radiation Oncology, Sun Yat-sen University Cancer Center

Study Record Dates

• First Submitted: August 6, 2026
• First Posted: August 17, 2026
• Study Start: September 1, 2026
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): December 31, 2028
• Last Updated: August 17, 2026

Record last verified: 2026-08

Data Sharing

• IPD Sharing: Will not share

Locations

CN (2)