Becotatug Vedotin Combined With Pucotenlimab for Locally Recurrent Resectable Head and Neck Squamous Cell Carcinoma

NCT07632339 | Recruiting Phase 2

• 1 other identifier: SH9H-2026-T316-1
• Study Type: interventional
• Target: 102
• Locations: 1 country
• Sites: 1

Brief Summary

This is a multicenter, randomized, controlled, Phase II clinical study designed to evaluate the efficacy and safety of neoadjuvant and adjuvant therapy with vebikotamab combined with Pucotenlimab compared to standard treatment in patients with locally recurrent resectable head and neck squamous cell carcinoma (HNSCC). Investigational Arm: The dosing regimen for the investigational arm is as follows: Pucotenlimab: 200 mg per dose, administered intravenously (IV) every 3 weeks (Q3W). No dose adjustments are permitted; however, dosing delays are allowed up to a maximum of 12 weeks from the date of the previous dose. This is administered for two preoperative cycles. Becotatug Vedotin: 2.3 mg/kg, administered IV Q3W for two preoperative cycles. Following neoadjuvant therapy, patients will undergo surgery at 4 weeks ± 7 days. Postoperatively (at 6 weeks ± 3 weeks), patients will be stratified for adjuvant therapy based on pathological response: Patients who achieve a major pathological response (MPR) and have no high-risk factors will receive 6 cycles of single-agent adjuvant Pucotenlimab (200 mg/dose, Q3W). Patients who do not achieve MPR or who present with high-risk factors will receive standard postoperative adjuvant therapy. Control Arm: Patients in the control arm will undergo upfront surgery followed by standard adjuvant therapy.

Conditions

Head and Neck Cancer

Outcome Measures

Primary Outcomes (1)

• 1 year events free survival rate

  the percentage of participants documented PD per RECIST 1.1 from enrollment in the neoadjuvant stage, or recurrent or death due to any cause, whichever occurred first.

  24 months

Secondary Outcomes (4)

• Progression Free Survival Per RECIST 1.1

  24 months

• MPR rate

  24 months

• Number of Participants Experiencing an Adverse Event (AE)

  24 months

• overall survival

  24 months

Study Arms (2)

Neoadjuvant treatment arm

EXPERIMENTAL

Pucotenlimab: 200 mg per dose, administered intravenously (IV) every 3 weeks (Q3W). No dose adjustments are permitted; however, dosing delays are allowed up to a maximum of 12 weeks from the date of the previous dose. This is administered for two preoperative cycles. Becotatug Vedotin: 2.3 mg/kg, administered IV Q3W for two preoperative cycles. Following neoadjuvant therapy, patients will undergo surgery at 4 weeks ± 7 days. Postoperatively (at 6 weeks ± 3 weeks), patients will be stratified for adjuvant therapy based on pathological response: Patients who achieve a major pathological response (MPR) and have no high-risk factors will receive 6 cycles of single-agent adjuvant Pucotenlimab (200 mg/dose, Q3W). Patients who do not achieve MPR or who present with high-risk factors will receive standard postoperative adjuvant therapy.

Drug: Becotatug Vedotin combined with Pucotenlimab

Standard treatment arm

ACTIVE COMPARATOR

Patients in the control arm will undergo upfront surgery followed by standard adjuvant therapy.

Procedure: surgery

Interventions

Becotatug Vedotin combined with Pucotenlimab DRUG

patients received 2 cycles of Pucotenlimab(200 mg per dose, q3w) and Becotatug Vedotin (2.3 mg/kg, Q3W) in the neoadjuvant stage, then patients will undergo surgery at 4 weeks ± 7 days. Postoperatively (at 6 weeks ± 3 weeks), patients will be stratified for adjuvant therapy based on pathological response: Patients who achieve a major pathological response (MPR) and have no high-risk factors will receive 6 cycles of single-agent adjuvant Pucotenlimab (200 mg/dose, Q3W). Patients who do not achieve MPR or who present with high-risk factors will receive standard postoperative adjuvant therapy.

Also known as: neoadjuvant arm

Neoadjuvant treatment arm

surgery PROCEDURE

Patients in the control arm will undergo upfront surgery followed by standard adjuvant therapy.

Also known as: Standard treatment arm

Standard treatment 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:

• Age between 18 and 75 years, inclusive, regardless of sex; Histologically or cytologically confirmed locally recurrent head and neck squamous cell carcinoma (HNSCC) that is amenable to curative surgical resection. Patients must not have received any prior systemic antineoplastic therapy for the recurrent disease. (Note: Prior systemic therapy as part of a multimodality treatment for locally advanced disease is permitted, provided that ≥6 months have elapsed from the completion of such therapy to the signing of the informed consent form); Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1; Estimated life expectancy ≥12 weeks; At least one measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Previously irradiated lesions may be considered measurable if disease progression has been documented at the site; Availability of tumor tissue for PD-L1 testing (paraffin-embedded specimens collected within 2 years or fresh tumor tissue);
• Adequate organ function, defined as follows (assessed within 14 days prior to the first dose of the investigational product):
• Bone Marrow: Absolute neutrophil count (ANC) ≥1.5×10⁹/L, platelets (PLT) ≥100×10⁹/L, hemoglobin (HB) ≥9 g/dL (no blood transfusions or blood component therapy within 14 days prior to screening); Liver \& Kidney: Serum total bilirubin (TBIL) ≤1.5 × upper limit of normal (ULN), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 × ULN (if hepatic metastasis is present, AST and ALT ≤5 × ULN are allowed). Serum creatinine ≤1.5 × ULN and calculated creatinine clearance ≥50 mL/min (using the Cockcroft-Gault formula); Coagulation: International Normalized Ratio (INR) and activated partial thromboplastin time (APTT) ≤1.5 × ULN (applies only to patients not receiving anticoagulant therapy; patients on anticoagulants must be within the therapeutic range); Thyroid Function: Thyroid-stimulating hormone (TSH) ≤1 × ULN (if TSH is abnormal, free triiodothyronine \[FT3\] and free thyroxine \[FT4\] levels must be evaluated; enrollment is permitted if FT3 and FT4 are within normal limits); Urinary Protein: Urine dipstick protein ≤1+. If urine dipstick protein is \>1+, a 24-hour urine collection is required, and the total protein must be ≤1 g/day; Cardiac Function: Normal cardiac function, defined as a normal electrocardiogram (ECG) or ECG abnormalities with no clinical significance, and left ventricular ejection fraction (LVEF) \>50% as determined by echocardiography.
• Women of childbearing potential must have a negative serum pregnancy test prior to the first dose of the investigational product; Sexually active men and women of childbearing potential must use highly effective contraception (e.g., oral contraceptives, intrauterine devices, sexual abstinence, or barrier methods combined with spermicides) throughout the entire study period and for 90 days after the end of treatment; The patient voluntarily agrees to participate in the study, signs the informed consent form, demonstrates good compliance, and agrees to cooperate with follow-up visits.

You may not qualify if:

• Presence of distant metastases or local lesions without surgical indications (Stage IVb or IVc); Disease progression occurring within 6 months following systemic therapy for locally advanced HNSCC; Re-irradiation to the head and neck region (including cervical, supraclavicular, and infraclavicular lymph nodes) within 6 months prior to enrollment; Prior treatment with PD-1/PD-L1/PD-L2/CTLA-4 antibodies, or agents targeting activating or inhibitory receptors on T cells (e.g., OX40, CD137); Prior treatment with antibody-drug conjugates (ADCs) bearing an MMAE payload; Participation in any other drug/treatment clinical trial within 4 weeks prior to the first dose of the investigational product, or currently participating in another trial; major surgery, unresolving adverse effects from prior surgery, live vaccines, or immunotherapy within 4 weeks prior to the first dose; radiotherapy within 2 weeks prior to the first dose; concurrent receipt of any other antineoplastic therapy; Any active autoimmune disease or history of autoimmune disease (including but not limited to: autoimmune hepatitis, interstitial pneumonitis, uveitis, enteritis, hepatitis, hypophysitis, vasculitis, nephritis, hyperthyroidism). Exceptions: Vitiligo not requiring systemic therapy is permitted; childhood asthma that has completely resolved and requires no intervention in adulthood is permitted. Asthma requiring medical intervention with bronchodilators is not permitted; Current use of immunosuppressants or systemic corticosteroids for immunosuppressive purposes (at doses \>10 mg/day prednisone equivalent or equivalent efficacy) that are still being used within 2 weeks prior to enrollment; History of other malignancies within the past 5 years, except for adequately treated basal cell carcinoma of the skin, cutaneous squamous cell carcinoma, early-stage prostate cancer, and carcinoma in situ of the cervix; Active pulmonary diseases (interstitial pneumonitis, pneumonia, obstructive pulmonary disease, asthma) or a history of active pulmonary tuberculosis;
• Any uncontrolled clinical conditions, including but not limited to:
• Persistent or active (severe) infections; Poorly controlled hypertension (persistent blood pressure \>150/90 mmHg); Poorly controlled diabetes mellitus; Cardiac diseases (New York Heart Association \[NYHA\] Class III/IV congestive heart failure or cardiac conduction blocks); Occurrence of any of the following within 6 months prior to the first dose: deep vein thrombosis (DVT) or pulmonary embolism (PE); myocardial infarction; severe or unstable arrhythmias or angina; percutaneous coronary intervention (PCI), acute coronary syndrome (ACS), or coronary artery bypass grafting (CABG); cerebrovascular accident (CVA), transient ischemic attack (TIA), or cerebral embolism; History of psychoactive substance abuse that cannot be discontinued, or a history of psychiatric disorders; Any other severe, acute, or chronic medical condition, or laboratory abnormalities that, in the investigator's judgment, may increase the risks associated with study participation or interfere with the interpretation of study results; Poor compliance, or any other circumstances that, in the investigator's judgment, render the patient unsuitable for participation in this trial.

Sponsors & Collaborators

• Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University: lead

Study Sites (1)

the Ninth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine

Shanghai, Shanghai Municipality, 200011, China

RECRUITING

MeSH Terms

Conditions

Head and Neck Neoplasms

Interventions

Surgical Procedures, Operative

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms

Study Officials

• Yue He, M.D.

  the Ninth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Guoxin Ren, M.D.

CONTACT

13916948812; renguoxincn@sina.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dr.

Study Record Dates

• First Submitted: June 3, 2026
• First Posted: June 8, 2026
• Study Start (Estimated): June 16, 2026
• Primary Completion (Estimated): June 16, 2028
• Study Completion (Estimated): June 16, 2029
• Last Updated: June 8, 2026

Record last verified: 2026-06

Locations

CN (1)