A Prospective, Single-arm, Phase II Clinical Trial of Becotatug Vedotin for Injection Combined With Pucotenlimab Injection as a First-line Treatment for Platinum-intolerant Advanced Head and Neck Squamous Cell Carcinoma

A Prospective, Single-arm, Phase II Clinical Trial of Becotatug Vedotin for Injection Combined With Pucotenlimab Injection as a First-line Treatment for Platinum-intolerant Advanced Head and Neck Squamous Cell Carcinoma

This study is a randomized, open-label, multi-center phase II trial evaluating the efficacy and safety of the becotatug vedotin in combination with pucotenlimab regimen in patients with advanced head and neck squamous cell carcinoma who are intolerant to platinum-based therapy.

1. Histologically or cytologically diagnosed as squamous cell carcinoma, with the lesion site located in the oral cavity, oropharynx, hypopharynx, larynx, etc.;
2. Recurrence and metastasis occurred after previous local treatment (surgery, radiotherapy, or concurrent chemoradiotherapy), with no possibility of cure, and no systemic treatment had been received previously, or previous induction or adjuvant treatment had been received, but the time from the end of the above treatment was ≥ 6 months;
3. Existence of distant metastasis at the time of initial treatment, or extensive local lesion range, and not curable after MDT assessment;
4. Patients who cannot tolerate platinum-based chemotherapy or do not accept cisplatin-based chemotherapy; Definition of cisplatin intolerance: Any of the following criteria met: age ≥ 70 years; mild or above hearing impairment; creatinine clearance rate < 50 ml/min (calculated according to the Cockcroft and Gault formula);
5. PS score ≤ 2 points;
6. At least one evaluable lesion according to the RECIST V1.1 standard;
7. Normal organ function is sufficient:

Bone marrow: Absolute neutrophil count (ANC) ≥ 1.5 × 109/L, platelet count ≥ 100 × 109/L, hemoglobin ≥ 90 g/L, and no blood transfusion or biological response modifiers (such as granulocyte and erythropoietin growth factors) treatment within 14 days before the first administration; Liver: ALT and AST ≤ 2.5 times the upper limit of normal value (for subjects with liver metastasis, AST and ALT ≤ 5 × ULN), total bilirubin ≤ 1.5 times the upper limit of normal value (for subjects with liver metastasis or confirmed/suspected Gilbert syndrome, TBIL ≤ 3 × ULN); serum albumin ≥ 30 g/L; Kidneys: Creatinine clearance rate (Ccr) ≥ 30 mL/min (calculated according to the Cockcroft and Gault formula)

Patients with any of the following conditions are not eligible to be included in this study:

1. Have a history of other primary malignant tumors within the past 3 years, except for skin basal cell carcinoma, superficial bladder cancer, skin squamous cell carcinoma, or in situ cervical cancer that have been completely resected;
2. Have peripheral neuropathy of grade ≥ 2 (according to CTCAE v5.0);
3. Have received any of the following treatments:
4. Received intravenous antibiotic treatment within 7 days before the first administration;
5. Received the study drug in another clinical trial within 4 weeks before the first administration;
6. Have received attenuated live vaccines within 4 weeks before the first administration, or have been vaccinated with inactivated seasonal influenza vaccine or approved live virus-free COVID-19 vaccine;
7. Have received systemic immunostimulatory drug treatment (including but not limited to interferons, interleukin-2, etc.) within 4 weeks before the first administration;
8. Have undergone major surgical treatment (such as abdominal, thoracic surgeries, etc., excluding diagnostic punctures, infusion device implantation, or digestive tract implantation, etc.) within 4 weeks before the first administration, or are expected to undergo major non-tumor-related surgical treatment during the new adjuvant therapy period;
9. Have clinically significant (i.e., active) cardiovascular diseases: cerebrovascular accidents/strokes/ myocardial infarction within 6 months before enrollment, unstable angina pectoris, congestive heart failure (NYHA II grade and above), or require drug treatment for severe arrhythmias;
10. Have evidence of active infections including hepatitis B (requiring both HBsAg positive, HBV DNA ≥ 2000 IU/ml, and exclusion of hepatitis caused by other factors), hepatitis C (requiring both anti-HCV antibody positive and HCV RNA result greater than the detection limit), or human immunodeficiency virus (HIV) infection; Uncontrolled active bacterial, other viral, fungal, rickettsial or parasitic infections, unless treated and resolved before the administration of the study drug;
11. Have a history of primary immunodeficiency or active autoimmune diseases, are using immunosuppressants or systemic hormone therapy (dose ≥ 10 mg/day of prednisone or equivalent hormone), and are still using it within 2 weeks before enrollment; Note: Type 1 diabetes, stable hypothyroidism due to hormone replacement therapy (including autoimmune thyroid disease-induced hypothyroidism), psoriasis, vitiligo or eczema patients can be enrolled, using local topical or inhaled glucocorticoids, or short-term (≤ 7 days) use of glucocorticoids for prevention or treatment of non-autoimmune and infrequent allergic diseases are excluded. ;
12. Has a history of ≥ grade 3 allergic reaction to any component of Viberceptotota monoclonal antibody or Putilimab injection;
13. Has a history of or is concurrently suffering from interstitial pneumonia, radiation pneumonia, severe chronic obstructive pulmonary disease, severe pulmonary insufficiency, symptomatic bronchospasm, etc.;
14. Has a history of organ transplantation, including allogeneic peripheral stem cell or bone marrow transplantation. After careful assessment, patients who have undergone autologous hematopoietic stem cell transplantation for ≥ 5 years and have normal bone marrow function (not dependent on blood transfusion) can be considered to participate in the study; Other conditions that the investigator deems unsuitable for participation in this clinical trial, including but not limited to severe mental illness, central nervous system disorders, drug abuse, etc.