Sacituzumab Tirumotecan Plus Immunotherapy for Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma

A Prospective, Single-Center, Open-Label Phase II Clinical Study of Sacituzumab Tirumotecan Combined With Immune Checkpoint Inhibitors for the Later-Line Treatment of Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma

This is a single-center, open-label phase 2 study evaluating sacituzumab tirumotecan in combination with an immune checkpoint inhibitor in patients with previously treated recurrent or metastatic head and neck squamous cell carcinoma.

Eligible patients will have recurrent or metastatic head and neck squamous cell carcinoma that has progressed after prior standard therapy including an immune checkpoint inhibitor. Sacituzumab tirumotecan, a TROP2-directed antibody-drug conjugate, will be administered by intravenous infusion every 2 weeks in combination with the patient's ongoing immune checkpoint inhibitor. Treatment will continue until disease progression, unacceptable toxicity, withdrawal of consent, initiation of new anticancer therapy, investigator decision, or other protocol-defined discontinuation criteria.

The primary endpoint is objective response rate (ORR), as assessed by the investigator according to RECIST v1.1. Secondary endpoints include disease control rate (DCR), progression-free survival (PFS), overall survival (OS), duration of response (DoR), and safety and tolerability.

Inclusion Criteria:

1. Male or female patients aged ≥18 years and <80 years at the time of signing the informed consent form.

2. Histologically or cytologically confirmed recurrent or metastatic head and neck squamous cell carcinoma, including locally recurrent disease not amenable to curative local therapy and distant metastatic disease.

3. Recurrent or metastatic head and neck squamous cell carcinoma after failure of prior standard therapy containing an immune checkpoint inhibitor. Treatment failure is defined as discontinuation of the current treatment due to disease progression. For patients with recurrent or metastatic disease, disease progression (PD) confirmed during systemic therapy or at the first tumor response assessment after completion of therapy will be considered treatment failure. Dose adjustment, treatment switching, or treatment discontinuation due to drug intolerance, treatment-related toxicity, patient preference, financial reasons, or other non-progression-related reasons will not be considered treatment failure.

4. At least one measurable lesion according to RECIST v1.1.

5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

6. No clinically significant contraindication to immune checkpoint inhibitor therapy as judged by the investigator.

7. Adequate major organ function, meeting the following criteria:

   • Hematology: white blood cell count (WBC) ≥4.0 × 10^9/L, absolute neutrophil count (ANC) ≥1.5 × 10^9/L, platelet count (PLT) ≥100 × 10^9/L, and hemoglobin (Hb) ≥90 g/L, without blood transfusion or blood products and without granulocyte colony-stimulating factor (G-CSF) or other hematopoietic growth factors within 14 days before assessment.
   • Serum chemistry: serum albumin ≥3.0 g/dL (30 g/L), total bilirubin (TBIL) ≤1.5 × upper limit of normal (ULN), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 × ULN, and blood urea nitrogen (BUN) and serum creatinine (Cr) ≤1.5 × ULN, or creatinine clearance ≥60 mL/min calculated using the Cockcroft-Gault formula.
   • Coagulation: adequate coagulation function, defined as international normalized ratio (INR) or prothrombin time (PT) ≤1.5 × ULN. For patients receiving anticoagulant therapy, PT must be within the intended therapeutic range for the anticoagulant.

8. Female patients of childbearing potential must have a negative serum or urine pregnancy test within 7 days before enrollment and agree to use effective contraception during the study and for 6 months after the last dose of study treatment. Male patients with partners of childbearing potential must agree to use effective contraception during the study and for 6 months after the last dose of study treatment.

9. Able to understand and voluntarily sign the informed consent form, and willing to comply with study procedures and follow-up.

Exclusion Criteria:

1. Participation in another interventional drug clinical trial within 4 weeks before enrollment.
2. Prior treatment with a TROP2-targeted therapy and/or a topoisomerase I inhibitor.
3. Prior intolerance to immune checkpoint inhibitor therapy, defined as permanent discontinuation of prior immunotherapy due to a grade ≥3 immune-related adverse event (irAE) according to CTCAE v5.0, or hypersensitivity to an immune checkpoint inhibitor, including grade ≥3 infusion-related reaction.
4. History of another malignancy within 5 years before enrollment, except for cured carcinoma in situ of the cervix, basal cell carcinoma of the skin, or squamous cell carcinoma of the skin.
5. Known history of hypersensitivity to any study drug or any of its components.
6. Positive human immunodeficiency virus (HIV) test or history of acquired immunodeficiency syndrome (AIDS); known active syphilis infection.
7. History of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation.
8. Receipt of a live vaccine within 30 days before the first dose of study treatment.
9. History of noninfectious interstitial lung disease (ILD) or noninfectious pneumonitis requiring steroid treatment; current ILD or noninfectious pneumonitis; or suspected ILD or noninfectious pneumonitis that cannot be excluded by imaging during screening. Patients with clinically significant pulmonary impairment due to comorbid pulmonary disease, including but not limited to pulmonary embolism within 3 months before the first dose, severe asthma, severe chronic obstructive pulmonary disease, restrictive lung disease, or pleural effusion, or any autoimmune, connective tissue, or inflammatory disease that may involve the lungs, such as rheumatoid arthritis, Sjögren's syndrome, or sarcoidosis, or history of total pneumonectomy, are also excluded.
10. Active autoimmune disease requiring systemic treatment within the past 2 years. Hormone replacement therapy is not considered systemic treatment, including type 1 diabetes mellitus, hypothyroidism requiring only thyroid hormone replacement, or adrenal or pituitary insufficiency requiring only physiologic corticosteroid replacement.
11. Active infection requiring systemic therapy within 2 weeks before the first dose of study treatment.
12. Any serious concomitant disease that, in the investigator's judgment, may compromise patient safety or interfere with completion of the study, including but not limited to uncontrolled hypertension, severe diabetes mellitus, or active infection.
13. Documented severe dry eye syndrome, severe meibomian gland disease and/or blepharitis, or history of corneal disease that may impair or delay corneal healing.
14. Pregnant or breastfeeding women; female patients of childbearing potential with a positive pregnancy test at baseline; or female patients of childbearing potential who are unwilling to use effective contraception during study treatment and for 6 months after the last dose of study treatment.
15. Any other condition that, in the investigator's judgment, makes the patient unsuitable for participation in this study.