Becotatug Vedotin (MRG003) in Combination With PD-1 Inhibitor Versus PD-1 Inhibitor for the Treatment of EGFR-positive, CPS≥1 Resectable Locally Advanced Head and Neck Squamous Cell Carcinoma

NCT07524452 | Recruiting Phase 3

• 1 other identifier: ZDWY.FSZLK.006
• Study Type: interventional
• Target: 430
• Locations: 1 country
• Sites: 1

Brief Summary

This study is a randomized, open-label, multicenter phase III trial designed to systematically evaluate the efficacy and safety of perioperative neoadjuvant and adjuvant therapy with Becotatug vedotin in combination with PD-1 inhibitor versus PD-1 inhibitor alone in patients with EGFR-positive, CPS ≥ 1 resectable locally advanced head and neck squamous cell carcinoma .

Conditions

Locally Advanced Head and Neck Squamous Cell Carcinoma

Keywords

Resectabl locally advanced head and neck squamous cell carcinoma; Becotatug Vedotin; perioperative neoadjuvant and adjuvant therapy

Outcome Measures

Primary Outcomes (1)

• Event-Free Survival Rate (EFS)

  Defined as the time from randomization to the first occurrence of disease progression, relapse, or death from any cause.

  3 years

Secondary Outcomes (13)

• Overall Survival (OS)

  3 years

• Distant Metastasis-Free Survival (DMFS)

  3 years

• Locoregional Relapse-Free Survival (LRRFS)

  3 years

• Objective Response Rate (ORR)

  After the completion of neoadjuvant therapy, prior to surgery.

• Disease Control Rate (DCR)

  After the completion of neoadjuvant therapy, prior to surgery.

Study Arms (2)

Becotatug vedotin plus pucotenlimab arm

EXPERIMENTAL

Patients receive Becotatug vedotin combined with pucotenlimab as neoadjuvant treatment prior to surgical resection and as adjuvant treatment after radiotherapy.

Drug: Neoadjuvant and Adjuvant Becotatug Vedotin; Drug: Neoadjuvant and Adjuvant Immunotherapy; Procedure: Surgery; Radiation: Adjuvant Radiotherapy; Drug: Adjuvant Cisplatin

pucotenlimab arm

ACTIVE COMPARATOR

Patients receive pucotenlimab as neoadjuvant treatment prior to surgical resection and as adjuvant duiring and after radiotherapy.

Drug: Neoadjuvant and Adjuvant Immunotherapy; Procedure: Surgery; Radiation: Adjuvant Radiotherapy; Drug: Adjuvant Cisplatin

Interventions

Neoadjuvant and Adjuvant Becotatug Vedotin DRUG

Neoadjuvant therapy with Becotatug Vedotin (Day 1, Q3W, 2 cycles); Adjuvant therapy after radiotherapy with Becotatug Vedotin ( Day 1, Q3W, for a total of 12 cycles).

Becotatug vedotin plus pucotenlimab arm

Neoadjuvant and Adjuvant Immunotherapy DRUG

Neoadjuvant immunotherapy with pucotenlimab (200mg, Day 1, Q3W, 2 cycles); Adjuvant immunotherapy duiring and after radiotherapy with pucotenlimab (200mg, Day 1, Q3W, for a total of 15 cycles).

Becotatug vedotin plus pucotenlimab arm; pucotenlimab arm

Surgery PROCEDURE

Radical surgery performed 3-4 weeks after neoadjuvant therapy, following a re-evaluation of surgical indications by the surgeon.

Becotatug vedotin plus pucotenlimab arm; pucotenlimab arm

Adjuvant Radiotherapy RADIATION

Radiotherapy is initiated 4-6 weeks after surgery. For the low-risk group, a total dose of 60 Gy in 30 fractions is delivered using intensity-modulated radiation therapy (IMRT). For the high-risk group, 66 Gy in 33 fractions is prescribed, or 70 Gy in 35 fractions for residual lesions, also using IMRT.

Becotatug vedotin plus pucotenlimab arm; pucotenlimab arm

Adjuvant Cisplatin DRUG

High-risk group：Cisplatin 100 mg/m² is administered via intravenous infusion on Day 1 of every 21-day cycle during radiotherapy, for a total of 3 cycles.

Becotatug vedotin plus pucotenlimab arm; pucotenlimab arm

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Voluntarily sign the informed consent form;
• Untreated, histologically confirmed head and neck squamous cell carcinoma (oral cavity, oropharynx, hypopharynx, or larynx), EGFR-positive, CPS ≥ 1, with clinical stage (AJCC 8th edition): p16-positive oropharynx: Stage III (T4N0-2M0); p16-negative oropharynx: Stage III or IVA; larynx/hypopharynx/oral cavity: Stage III or IVA;
• Eligible for curative-intent surgery as determined by the surgeon;
• Age: 18 to 75 years;
• ECOG performance status 0-1;
• Life expectancy greater than 6 months;
• At least one measurable lesion per RECIST 1.1;
• Adequate organ function, based on meeting all of the following criteria (no receipt of blood components or hematopoietic growth factors within 14 days prior to testing): hemoglobin ≥ 90 g/L; absolute neutrophil count ≥ 1.5 × 10⁹/L; platelet count ≥ 100 × 10⁹/L; serum albumin ≥ 28 g/L; total bilirubin ≤ 1.5 × upper limit of normal (ULN); ALT and AST ≤ 2.5 × ULN; serum creatinine ≤ 1.5 × ULN, with creatinine clearance ≥ 50 mL/min; activated partial thromboplastin time and international normalized ratio (INR) ≤ 1.5 × ULN (patients receiving a stable dose of anticoagulant therapy, such as low molecular weight heparin or warfarin, may be enrolled if INR is within the expected therapeutic range for the anticoagulant). Thyroid-stimulating hormone (TSH) ≤ ULN; if abnormal, T3 and T4 levels should be assessed, and patients with normal T3 and T4 levels may be enrolled;
• Baseline left ventricular ejection fraction (LVEF) ≥ 50% as measured by multigated acquisition (MUGA) scan or echocardiography (ECHO);
• Women of childbearing potential must agree to use contraception (e.g., intrauterine device, contraceptive pill, or condom) during the treatment period and for 3 months after the last dose;
• Good compliance.

You may not qualify if:

• Pregnant or breastfeeding women.
• History of allergy to PD-1 inhibitors.
• History of other malignancies within the past 5 years or at enrollment, with the exception of cured basal cell carcinoma of the skin, carcinoma in situ of the cervix, and thyroid papillary tumors.
• Residual toxicity from prior anti-tumor therapy (including immunotherapy, targeted therapy, chemotherapy, or radiotherapy, etc.) other than alopecia, fatigue, and grade 2 hypothyroidism, or clinically significant laboratory abnormalities greater than grade 1 (CTCAE v5.0).
• Uncontrolled cardiac conditions or diseases, such as: ① NYHA Class II or greater heart failure, ② unstable angina, ③ myocardial infarction within 1 year, and ④ patients with clinically significant ventricular arrhythmias requiring intervention.
• Grade ≥ 2 peripheral neuropathy (per CTCAE v5.0).
• Pulmonary embolism or deep vein thrombosis within 3 months prior to enrollment (excluding catheter-related thrombosis from infusion ports or PICC lines).
• Active bleeding, history of coagulation disorders, or patients receiving coumarin anticoagulant therapy.
• Known hypersensitivity to any component or excipient of vibecotamab (citric acid monohydrate, sodium citrate dihydrate, trehalose dihydrate, sodium chloride, and polysorbate 80), or known grade ≥ 3 hypersensitivity reaction to other prior anti-EGFR agents (including investigational drugs) or other monoclonal antibodies.
• Receipt of any of the following treatments:
• ① Any investigational drug prior to the first dose of the current study drug.
• ② Concurrent participation in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period.
• ③ Use of systemic corticosteroids (more than 10 mg of prednisone or equivalent per day) or other immunosuppressive agents within 2 weeks prior to the first dose of study drug, except for the use of corticosteroids for localized inflammation, prevention of allergies, or nausea and vomiting. In the absence of active autoimmune disease, inhaled or topical steroids and adrenal corticosteroid replacement doses greater than 10 mg prednisone equivalent per day are permitted.
• ④ Administration of live vaccines within 4 weeks prior to the first dose of study drug.
• ⑤ Major surgery or severe trauma within 4 weeks prior to the first dose of study drug.

Sponsors & Collaborators

• Ming-Yuan Chen: lead

Study Sites (1)

The Fifth Affiliated Hospital,Sun Yat-sen University

Zhuhai, Guangdong, 519099, China

RECRUITING

MeSH Terms

Interventions

Neoadjuvant Therapy; Surgical Procedures, Operative; Radiotherapy, Adjuvant

Intervention Hierarchy (Ancestors)

Combined Modality Therapy; Therapeutics; Radiotherapy

Central Study Contacts

Mingyuan Chen

CONTACT

+86 18124188280; chmingy@mail.sysu.edu.cn

Rui You

CONTACT

+86 13580439820; your5@mail.sysu.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor, Chief physician

Study Record Dates

• First Submitted: March 28, 2026
• First Posted: April 13, 2026
• Study Start: February 6, 2026
• Primary Completion (Estimated): February 28, 2031
• Study Completion (Estimated): February 28, 2032
• Last Updated: April 13, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)