Neoadjuvant Sacituzumab Govitecan Plus Tagitanlimab for R... | NCT07492914

NCT07492914

Protocol Section

Identification Module

Results Section

No data available

No data is available for this block.

Annotation Section

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No data is available for this block.

Document Section

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No data is available for this block.

Derived Section

Miscellaneous Info Module

Status Module

Description Module

Brief Summary

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.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Sacituzumab govitecan + Tagitanlimab Neoadjuvant Therapy	Experimental	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 Drug: Tagitanlimab

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Sacituzumab Govitecan	Drug	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.

Outcomes Module

Primary Outcomes

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 Outcomes

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.

Eligibility Module

Eligibility Criteria

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.