Neoadjuvant Becotatug Vedotin Plus Pucotenlimab in Locally Advanced Oral and Oropharyngeal Squamous Cell Carcinoma (OSCC)

A Single-Arm, Prospective Phase II Clinical Study of Becotatug Vedotin Combined With Pucotenlimab as Neoadjuvant Therapy in Locally Advanced Oral and Oropharyngeal Squamous Cell Carcinoma

The purpose of this study is to evaluate the effectiveness and safety of the combination therapy of Becotatug Vedotin with Pucotenlimab as a possible neoadjuvant therapyand for locally advanced oral/pharyngeal squamous cell carcinoma.

Study Overview

• Status: Not yet recruiting
• Conditions: Locally Advanced Oral and Oropharyngeal Squamous Cell Carcinoma
• Intervention / Treatment: Drug: MRG003+Pucotenlimab

Detailed Description

Approximately 60% of patients with oral/oropharyngeal squamous cell carcinoma (OSCC) are found to be in the local advanced stage. Even if they actively undergo comprehensive sequential treatment such as surgery, radiotherapy, and chemotherapy, the 5-year survival rate is still less than 50%. According to both the NCCN and the CSCO head and neck cancer treatment guidelines, radical surgery is the main treatment strategy for locally advanced OSCC, and adjuvant radiotherapy or chemotherapy/radiotherapy. However, the high treatment failure rate and disease recurrence rate are still the fundamental reasons for its poor prognosis. In recent years, neoadjuvant therapy has been proven to reduce the burden of local diseases in multiple tumor types, thereby improving surgical outcomes, reducing the risk of distant metastasis, and predicting prognosis based on the patient's pathological response. The combination of anti-PD-1/PD-L1 monoclonal antibodies and EGFR ADC drugs has a synergistic anti-tumor effect, and this combination therapy is worth exploring in the neoadjuvant treatment of locally advanced oral/oropharyngeal squamous cell carcinoma. This prospective, open label, single arm, phase II, single center exploratory study aims to evaluate the efficacy and safety of the combination therapy of Becotatug Vedotin and Pucotenlimab as neoadjuvant therapy in patients with locally advanced oral/oropharyngeal squamous cell carcinoma.

• Study Type: Interventional
• Enrollment (Estimated): 26
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Tong Ji, PhD; Phone Number: 86-13651658767; Email: ji.tong@zs-hospital.sh.cn
• Study Contact Backup: Name: Chengzhong Lin, PhD; Phone Number: 86-18916535332; Email: lin.chengzhong@zs-hospital.sh.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Participants must have histologically or cytologically confirmed oral/oropharyngeal squamous cell carcinoma (including tongue, lips, gums, cheeks, floor of mouth, hard palate, soft palate, posterior molar area, lateral pharyngeal wall, posterior pharyngeal wall, tonsils). PD-L1 expression score (CPS score) >1, EGFR expression score (IHC) >90%+.
• Participants must diagnosed with clinical staging III or IVa (AJCC, 8th edition), without evidence of distant metastasis (M0) based on PET/CT or chest, abdominal and pelvic CT scans, and standard treatment is recommended, including surgical resection and adjuvant radiotherapy+/- chemotherapy.
• Age ranges from 18 to 75 years old.
• ECOG performance status 0 or 1.
• Expected survival ≥ 3 months.
• Participants must have not received treatment for before.
• There must be at least one clinically assessable lesion according to the RECIST V1.1 criteria prior to treatment.
• The participants may have any human papillomavirus (HPV) status of the tumor. Patients with oropharyngeal cancer need to undergo HPV testing, including p16 immunohistochemistry and/or confirmatory HPV polymerase chain reaction (PCR) or in situ hybridization (ISH) testing.
• Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation, and continue contraception for 12 months after the end of treatment. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.
• Participants must have adequate organ and marrow function as defined below: The function of important organs meets the following requirements: (1) normal bone marrow reserve function, white blood cell (WBC) ≥ 3.0 × 10 ^ 9/L; Neutrophil count (NEUT) ≥ 1.5 × 10 ^ 9/L, platelet count (PLT) ≥ 100 × 10 ^ 9/L, hemoglobin (Hb) ≥ 90 g/L; (2) Normal renal function or serum creatinine (SCr) ≤ 1.5 times the upper limit of normal (ULN) or creatinine clearance rate ≥ 50 ml/min (Cockcroft Gault formula); (3) Normal liver function or total bilirubin (TBIL) ≤ 1.5 times the upper limit of normal (ULN); AST or ALT levels ≤ 3 times the upper limit of normal (ULN); (4) Thyroid stimulating hormone (TSH) ≤ 1 × ULN (if abnormal, FT3 and FT4 levels should be examined simultaneously. If FT3 and FT4 levels are normal, they can be included in the group).
• The participants voluntarily joined this study, signed an informed consent form, had good compliance, and cooperated with follow-up.

Exclusion Criteria:

• Squamous cell carcinoma with primary site of nasopharynx or skin.
• Diagnosed with malignant diseases other than head and neck squamous cell carcinoma within 3 years before the first administration (excluding Radical treated basal cell carcinoma of the skin, squamous cell carcinoma of the skin, and/or curative excised carcinoma in situ)
• Has received therapy treatment with anti-PD-1 antibody, anti-PD-L1 antibody, anti-PD-L2 antibody, or anti-CTLA-4 antibody (or any other antibody acting on T cell co stimulatory or checkpoint pathways).
• Has received live or attenuated vaccines within 30 days prior to the first dose of Sintilimab, inactivated vaccines are allowed.
• Has received immunosuppressive drugs within 14 days prior to the first dose of study drug, nasal and inhaled corticosteroids or physiological doses of systemic corticosteroids (i.e. not exceeding 10 mg/day of prednisolone or other corticosteroids of equivalent physiological doses) are allowed.
• Has an active infection that requires systematic treatment; Has a history of non -infectious pneumonia/interstitial lung disease requiring steroid treatment, or current pneumonia/interstitial lung disease; Has a known history of hepatitis B (defined as positive for hepatitis B surface antigen [HBsAg]) or known history of active hepatitis C virus (defined as detection of HCV RNA [qualitative]) infection; - - Has a known history of human immunodeficiency virus (HIV) infection.
• Has received allogeneic tissue/solid organ transplantation.
• Has not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities > Grade 2) with the exception of alopecia.
• Has obvious cardiovascular abnormalities (such as myocardial infarction, superior vena cava syndrome, and heart disease grade 2 or above diagnosed according to the New York Heart Association (NYHA) classification criteria within 3 months prior to the enrollment)。
• Has severe clinical infection (>NCI-CTCAE 5.0 Level 2 infection);
• Has uncontrollable hypertension (systolic blood pressure>150mmHg and/or diastolic blood pressure>90mmHg after treatment with antihypertensive drugs) or clinically significant cardiovascular diseases - such as cerebrovascular accidents (≤ 6 months before enrollment), myocardial infarction (≤ 6 months before enrollment), unstable angina, congestive heart failure classified as Grade II or above by the New York Heart Association (NYHA), or severe arrhythmias that cannot be controlled with medication or have potential impact on experimental treatment.
• Pregnant women are not allowed to participate. Breast-feeding women who participate in this study should stop breast-feeding.
• Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
• Has participated in other clinical studies within 30 days prior to enrollment.
• Other situations that researchers consider unsuitable for participation in the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: combined treatment; Becotatug Vedotin + Pucotenlimab	Drug: MRG003+Pucotenlimab; The participants will receive Pucotenlimab 200 mg (each 3-week/cycle) and Becotatug Vedotin (2.3mg/kg, each 3-week/cycle) for 2 cycles bofore surgery

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of Major Pathological Response (mPR)	Major pathologic response (mPR) is defined as having ≤ 10% invasive squamous cell carcinoma within the resected primary tumor specimen and all sampled regional lymph nodes as assessed by pathologists. Rate is the proportion of treated participants who experienced mPR	2 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
1 year Event-free Survival (EFS) Rate	EFS is the time from the date of study entry to the date of first record of disease progression as defined by RECIST 1.1	12 months
1 year Overall Survival (OS) Rate	OS is the time from study entry to death due to any cause	12 months
Adverse Events (AEs)	Number of participants experiencing any sign, symptom, disease, or worsening of preexisting conditions temporally associated with the experimental interventions or irrespective of the experimental interventions	24 months
Rate of Pathologic complete response (pCR)	Pathologic complete response (PCR) is defined as having no invasive squamous cell carcinoma within the resected primary tumor specimen and all sampled regional lymph nodes as assessed by pathologists. Rate is the proportion of treated participants who experienced PCR.	2 months
2 year Event-free Survival (EFS) Rate		24 months
2 year Overall Survival (OS) Rate		24 months

Collaborators and Investigators

• Sponsor: Shanghai Zhongshan Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2026
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): August 1, 2029

Study Registration Dates

• First Submitted: April 15, 2026
• First Submitted That Met QC Criteria: April 15, 2026
• First Posted (Actual): April 22, 2026

Study Record Updates

• Last Update Posted (Actual): April 22, 2026
• Last Update Submitted That Met QC Criteria: April 15, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Head and Neck Neoplasms; Neoplasms, Glandular and Epithelial; Carcinoma; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck
• Other Study ID Numbers: B2026-172R

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No