Neoadjuvant Sacituzumab Govitecan Plus Tagitanlimab for Resectable Head and Neck Squamous Cell Carcinoma

A Single-Arm, Phase II Prospective Study Of Lucanoximab Combined With Tagolimab As Neoadjuvant Therapy For Resectable Head And Neck Squamous Cell Carcinoma

The goal of this clinical trial is to evaluate the anti-tumor activity, safety and tolerability of the combination of Sacituzumab govitecan and Tagitanlimab as neoadjuvant therapy in patients with resectable head and neck squamous cell carcinoma (HNSCC). It will also explore potential biomarkers related to the efficacy of this combined therapy. The main questions it aims to answer are:

Does the combination of Sacituzumab govitecan and Tagitanlimab improve the major pathological response rate (MPR) in patients with resectable HNSCC?

What adverse reactions (side effects) do participants experience when receiving this combined neoadjuvant therapy?

Does this combined therapy improve participants' objective response rate (ORR), survival time and quality of life?

This is a single-arm, open-label, prospective Phase II clinical study conducted at West China Hospital of Sichuan University. A total of 30 eligible patients will be enrolled, and no placebo control will be used. The study will evaluate the efficacy and safety of the combined therapy by monitoring clinical indicators, pathological results and adverse events throughout the trial.

Participants will:

Receive Sacituzumab govitecan (5mg/kg) and Tagitanlimab (900mg) intravenously every 2 weeks, for a total of 2 treatment cycles.

Patients will undergo surgical resection 3-6 weeks after completion of neoadjuvant therapy. Adjuvant therapy (concurrent chemoradiotherapy or radiotherapy alone) will be administered according to pathological risk factors, together with 15 cycles of Tagitanlimab as adjuvant immunotherapy.

Visit the clinic regularly for physical examinations, laboratory tests (such as blood routine, liver and kidney function), imaging examinations (such as head and neck MRI/CT) and safety checkups according to the study schedule.

Provide biological samples (peripheral blood, tumor tissue, saliva, feces) at specified time points for biomarker detection.

Complete quality-of-life questionnaires (such as EORTC QLQ-C30) regularly to assess changes in daily functioning.

Note: Participants will not be charged for the study drugs (Sacituzumab govitecan and Tagitanlimab ), and will receive appropriate subsidies for study-related visits and blood collection. The research team will provide active treatment and corresponding compensation if participants experience study-related adverse reactions.

Study Overview

• Status: Recruiting
• Conditions: Resectable Head and Neck Squamous Cell Carcinoma
• Intervention / Treatment: Drug: Sacituzumab Govitecan; Drug: Tagitanlimab

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Hong-Shuai Li, Dr; Phone Number: +86-18384262516; Email: lihongshuai456@163.com

Study Locations

• China
  • Sichuan
    • Chengdu, Sichuan, China, 610041
      • Recruiting
      • West China Hospital of Sichuan University
      • Contact: Hong-Shuai Li; Phone Number: +86-18384262516; Email: lihongshuai456@163.com
      • Contact: Xing-Chen Peng; Email: pxx2014@163.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Aged 18 years and above, of any gender.
• Histopathologically confirmed resectable head and neck squamous cell carcinoma (HNSCC), excluding nasopharyngeal, salivary gland, and thyroid malignant tumors; surgically assessed as resectable or potentially resectable.
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2.
• Sufficient organ and bone marrow function, meeting the following: absolute neutrophil count (NEUT) ≥1.5×10⁹/L, platelet count (PLT) ≥80×10⁹/L, hemoglobin ≥8 g/dL; aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5×upper limit of normal (ULN), total bilirubin (TBIL) ≤1.5×ULN; serum creatinine (Cr) ≤1.5×ULN or creatinine clearance rate (CCR) >60 mL/min; international normalized ratio (INR) ≤1.5, activated partial thromboplastin time (APTT) ≤1.5×ULN.
• Voluntarily participate in the study, sign the informed consent form, and be able to comply with scheduled study visits and relevant procedures in the protocol.

Exclusion Criteria:

• A history of other malignant tumors within the past 5 years, except for cured and non-recurrent malignancies (e.g., basal cell carcinoma, cutaneous squamous cell carcinoma, superficial bladder cancer, cervical carcinoma in situ).
• Active autoimmune disease or relevant medical history (except for type 1 diabetes mellitus under stable insulin therapy), including but not limited to immune neurological diseases, systemic lupus erythematosus, inflammatory bowel disease, autoimmune hepatitis, toxic epidermal necrolysis, or Stevens-Johnson syndrome.
• A history of allergic diseases or severe drug allergy (anaphylaxis requiring hospitalization); known hypersensitivity to anti-PD-L1 antibodies, TROP2 antibody-drug conjugates (ADCs), or excipients of the study drugs.
• Prior anti-tumor treatment involving anti-PD-1/PD-L1 antibodies, anti-CTLA-4 antibodies, TROP2 ADCs, or anti-tumor vaccine therapy.
• Receipt of a live infectious vaccine within 4 weeks prior to the first dose or planned vaccination during the study period; major surgery or severe trauma within 4 weeks prior to the first dose.
• Systemic use of corticosteroids (>10 mg/day prednisone equivalent) or other immunosuppressants within 14 days prior to the first dose (inhaled or topical steroids and adrenal replacement therapy are permitted).
• Severe medical conditions, including New York Heart Association (NYHA) class II or higher heart failure, ischemic heart disease, clinically significant arrhythmias requiring intervention, left ventricular ejection fraction (LVEF) <50% on echocardiography, or prolonged QTc interval (males >450 msec, females >470 msec).
• A known history of interstitial lung disease or high clinical suspicion of interstitial lung disease; active pulmonary tuberculosis or uncontrolled previous tuberculosis infection.
• Hyperthyroidism or organic thyroid disease (patients with hypothyroidism under stable thyroid hormone replacement therapy are eligible for enrollment).
• Active infection, unexplained fever within 48 hours prior to the first dose, or systemic antibiotic use within 1 week prior to signing the informed consent form.
• Active hepatitis B (HBV DNA ≥2000 IU/ml or ≥10⁴ copies/ml), active hepatitis C (positive anti-HCV and HCV RNA above the lower limit of detection), positive HIV antibody, or a history of acquired immunodeficiency syndrome (AIDS).
• A definite history of neurological or psychiatric diseases such as epilepsy or dementia.
• A history of drug or alcohol abuse.
• Pregnant or lactating females; patients (or their partners) planning pregnancy, having unprotected sexual intercourse, or refusing to take effective contraceptive measures during the study and for 3 months after study completion.
• Receipt of other investigational drugs within 4 weeks prior to the first dose, or concurrent participation in other interventional clinical studies (observational or follow-up interventional studies are excluded).
• Other circumstances deemed unsuitable for study participation by the investigator.

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: Sacituzumab govitecan + Tagitanlimab Neoadjuvant Therapy; Eligible patients with resectable head and neck squamous cell carcinoma (HNSCC) will receive neoadjuvant combination therapy of Sacituzumab govitecan and Tagitanlimab for 2 sequential 2-week treatment cycles. Sacituzumab govitecan is administered intravenously at a dose of 5mg/kg every 2 weeks, and Tagitanlimab is administered intravenously at a fixed dose of 900mg every 2 weeks, with both agents delivered in the same cycles. Within 3-6 weeks after the completion of neoadjuvant therapy, patients will undergo surgical resection of the primary HNSCC tumor and regional lymph nodes. Postoperative adjuvant therapy will commence 4-6 weeks post-surgery. Patients with pathological high-risk factors (e.g., positive surgical margins, extranodal extension) will receive concurrent chemoradiotherapy plus 15 cycles of taglixlimab adjuvant immunotherapy, while patients with general risk factors (e.g., pT3/pT4, pN2/pN3) will be treated with radiotherapy combined with the same 15-cycle Tagitanlimab.

Drug: Sacituzumab Govitecan; Humanized anti-TROP2 antibody-drug conjugate (ADC) linked to a topoisomerase I inhibitor via a stable linker, featuring high tumor targeting and efficient cytotoxic drug release. Administered intravenously at 5mg/kg every 2 weeks for 2 cycles (90±15 minutes infusion per dose) as neoadjuvant therapy for resectable head and neck squamous cell carcinoma (HNSCC), delivering targeted cytotoxic effects to TROP2-overexpressing tumor cells to inhibit tumor growth.; Drug: Tagitanlimab; Humanized IgG1κ anti-PD-L1 monoclonal antibody that blocks the PD-1/PD-L1 signaling pathway to restore T cell-mediated anti-tumor immunity and reverse tumor immune escape. Administered intravenously at a fixed 900mg dose every 2 weeks for 2 cycles (120 minutes infusion per dose) as neoadjuvant therapy for resectable head and neck squamous cell carcinoma (HNSCC), used in combination with Sacituzumab Govitecan to achieve synergistic anti-tumor activity.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Major Pathological Response Rate (MPR)	Major Pathological Response Rate (MPR) is defined as the proportion of enrolled patients with residual viable tumor (RVT) ≤10% in the primary tumor and regional lymph node resection specimens after completion of 2 cycles of neoadjuvant Sacituzumab Govitecan plus Tagitanlimab therapy, assessed per immune-related pathological response criteria (irPRC) by independent pathological reviewers. MPR is the primary efficacy endpoint to evaluate the anti-tumor activity of the combined neoadjuvant regimen in resectable head and neck squamous cell carcinoma (HNSCC).	Assessed at the time of surgical resection (3 to 6 weeks after the completion of neoadjuvant therapy)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR)	Objective Response Rate (ORR) is defined as the proportion of enrolled patients achieving a confirmed complete response (CR) or partial response (PR) in tumor lesions after 2 cycles of neoadjuvant Sacituzumab Govitecan plus Tagitanlimab therapy, assessed per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 by independent radiological reviewers. ORR reflects the short-term anti-tumor efficacy of the combined neoadjuvant regimen on measurable HNSCC lesions.	Assessed at 3 to 6 weeks after the completion of neoadjuvant therapy (prior to surgical resection)
Event-Free Survival (EFS)	Event-Free Survival (EFS) is defined as the time from the first administration of neoadjuvant Sacituzumab Govitecan plus Tagitanlimab to the first occurrence of any study event, including radiologically or pathologically confirmed disease progression, local/distant tumor recurrence, or all-cause mortality. EFS evaluates the medium-term disease control efficacy of the combined regimen in resectable HNSCC patients.	Assessed up to 2 years after the first dose of neoadjuvant therapy (with regular follow-up every 3-4 months)
Overall Survival (OS)	Overall Survival (OS) is defined as the time from the first administration of neoadjuvant Sacituzumab Govitecan plus Tagitanlimab to all-cause mortality in enrolled patients. OS is a key endpoint reflecting the long-term survival benefit of the combined neoadjuvant regimen for resectable HNSCC patients, with survival status monitored through regular clinical follow-up.	Assessed up to 5 years after the first dose of neoadjuvant therapy (follow-up every 6 months for years 3-5, annually after year 5)
Incidence and Severity of Treatment-Related Adverse Events (TRAEs)	Incidence and severity of Treatment-Related Adverse Events (TRAEs) are defined as all adverse medical events judged to be related to Sacituzumab Govitecan and/or Tagitanlimab during the entire study period, graded per the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 5.0. This endpoint evaluates the safety and tolerability of the combined neoadjuvant regimen in resectable HNSCC patients.	Assessed from the first dose of neoadjuvant therapy to 90 days after the last study drug administration (with 30-day post-treatment safety follow-up)
Health-Related Quality of Life (HRQoL) Assessed by EORTC QLQ-C30	Health-related quality of life (HRQoL) was assessed via the validated European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30), which measures physical, emotional, social and cognitive function, as well as cancer-related symptom burden in malignant tumor patients. HRQoL scores at baseline and post-treatment were compared to quantify the combined neoadjuvant regimen's impact on patients' daily function and overall well-being. Scale Specifications: All EORTC QLQ-C30 subscales (functional/symptom) and the global health status/QoL scale are scored 0-100. Higher scores reflect better functional status/global health, while higher scores on symptom scales indicate more severe symptom burden.	Assessed at baseline (prior to the initiation of neoadjuvant therapy), post-neoadjuvant therapy (3-6 weeks after the completion of neoadjuvant treatment), and at 6 and 12 months following surgical resection.

Collaborators and Investigators

• Sponsor: West China Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): May 11, 2026
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): March 31, 2031

Study Registration Dates

• First Submitted: March 19, 2026
• First Submitted That Met QC Criteria: March 19, 2026
• First Posted (Actual): March 25, 2026

Study Record Updates

• Last Update Posted (Actual): May 13, 2026
• Last Update Submitted That Met QC Criteria: May 10, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Head and Neck Neoplasms; sacituzumab govitecan
• Other Study ID Numbers: 2025-2634

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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