A Randomized, Non-comparative, Multicenter Phase II Clinical Trial of Becotatug Vedotin Combined With or Without Immune Checkpoint Inhibitors (Penpulimab/Ivonescimab) in the Neoadjuvant Treatment of Resectable Locally Advanced Head and Neck Squamous Cell Carcinoma
概览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 120
- 主要终点
- pCR
概览
简要总结
A Randomized, Non-comparative, Multicenter Phase II Clinical Trial of Becotatug Vedotin Combined with or without Immune Checkpoint Inhibitors (Penpulimab/Ivonescimab) in the Neoadjuvant Treatment of Resectable Locally Advanced Head and Neck Squamous Cell Carcinoma (LAHNSCC). This proposed study will evaluate the efficacy and safety of preoperative administration of Becotatug Vedotin Combined with or without Immune Checkpoint Inhibitors (Penpulimab/Ivonescimab) in LAHNSCC who are eligible for resection.
详细描述
In this study, eligible patients will be randomized in a 1:1:1 ratio to either the Becotatug Vedotin treatment group (Cohort 1), or the Becotatug Vedotin combined with Penpulimab treatment group (Cohort 2), or the Becotatug Vedotin combined with Ivonescimab treatment group (Cohort 3). Pathological response rate will be the primary outcome measures. Adverse events will also be recorded.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age: 18 - 70 years old, gender not restricted;
- •Histopathologically diagnosed as squamous cell carcinoma of the head and neck (including oral cancer, laryngeal cancer, hypopharyngeal cancer, and oropharyngeal cancer, etc.);
- •Patients with resectable locally advanced head and neck squamous cell carcinoma (LA-HNSCC);
- •Eastern Cooperative Oncology Group (ECOG) score of 0 or 1;
- •Have not received any treatment for head and neck squamous cell carcinoma before, including drug treatment, radiotherapy, surgical treatment, etc.;
- •No distant metastasis;
- •The patient has the intention for radical treatment;
- •Good hematopoietic function (total white blood cell count ≥ 3.0×109 /L, absolute lymphocyte count ≥ 0.8×109/L, absolute neutrophil count ≥ 1.5×109/L, platelet count ≥ 100×109 /L, hemoglobin ≥ 90g/L) and no blood transfusion or biological response modifiers (such as granulocyte growth factors, erythropoietin growth factors, etc.) treatment within 14 days before the first administration;
- •Good liver function (total bilirubin (TBIL) ≤ 1.5×ULN; alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and alkaline phosphatase (ALP) ≤ 2.5×ULN; serum albumin ≥ 28 g/L);
- •Good renal function (serum creatinine ≤ 1.5 times ULN or calculated creatinine clearance rate ≥ 50 mL/min (Cockcroft-Gault formula), urine protein less than 2+, or 24-hour urine protein quantification \< 1g);
排除标准
- •Has received any form of anti-tumor treatment before;
- •Patients with allergic constitution and congenital immune deficiency;
- •Has undergone organ transplantation before;
- •Has a history of severe bleeding tendency or coagulation dysfunction; had significant clinical bleeding symptoms within 1 month before the study treatment, including but not limited to gastrointestinal bleeding and hemoptysis; had continuous anticoagulation treatment within 10 days before the study treatment;
- •Has experienced thromboembolic events such as cerebrovascular accidents (including transient ischemic attacks, cerebral hemorrhage, cerebral infarction), deep vein thrombosis and pulmonary embolism within 6 months before the study treatment;
- •Has active autoimmune or inflammatory diseases, or has a related history, including inflammatory bowel disease (such as colitis or Crohn's disease), diverticulitis (except diverticular disease), systemic lupus erythematosus, sarcoidosis syndrome or Wegener's syndrome (such as granulomatous vasculitis, Gray's disease, rheumatoid arthritis, pituitary inflammation and uveitis). There are the following exceptions: patients with vitiligo or alopecia; patients with stable hypothyroidism after hormone replacement therapy (such as after Hashimoto's thyroiditis); any patients with chronic skin diseases that do not require systemic treatment; patients who can be included within the past 5 years without active diseases, but only after consultation with the study doctor;
- •Active infections, including tuberculosis or human immunodeficiency virus (HIV 1/2 antibody positive);
- •Uncontrolled complications, including but not limited to: receiving study treatment for persistent or active infections (except HBV or HCV), symptomatic congestive heart failure, uncontrolled diabetes, uncontrolled hypertension, unstable angina pectoris, uncontrolled arrhythmia, active interstitial lung disease, severe chronic gastrointestinal diseases with diarrhea, or conditions that may limit compliance with study requirements, increase the risk of adverse events or affect the subject's ability to provide written informed consent;
- •Pregnant or lactating women;
- •The patient does not agree to use effective contraceptive measures during the treatment period and within the following 3 months;
研究组 & 干预措施
Becotatug Vedotin
Subjects receive 3 cycles of Becotatug Vedotin (2.3mg/kg, ivgtt, every 3 weeks, D1). Dose adjustments are allowed based on toxicity. Surgery will be performed within 2 to 4 weeks after the completion of neoadjuvant therapy, with subsequent adjuvant radiotherapy or chemoradiotherapy based on risk factors after surgery.
干预措施: Becotatug Vedotin (Drug)
Becotatug Vedotin Combined with Penpulimab
Subjects receive 3 cycles of Becotatug Vedotin (2.3mg/kg, ivgtt, every 3 weeks, D1) and 3 cycles of Penpulimab (200mg, ivgtt, every 3 weeks, D1). Surgery will be performed within 2 to 4 weeks after the completion of neoadjuvant therapy, with subsequent adjuvant radiotherapy or chemoradiotherapy based on risk factors after surgery. Subjects will receive Penpulimab treatment for 14 cycles following the completion of radiotherapy.
干预措施: Becotatug Vedotin Combined with Penpulimab (Drug)
Becotatug Vedotin Combined with Ivonescimab
Subjects received 3 cycles of Becotatug Vedotin (2.3mg/kg, ivgtt, every 3 weeks, D1) and 3 cycles of Ivonescimab (10mg/kg, ivgtt, every 3 weeks, D1). Dose adjustments are allowed based on toxicity. Surgery will be performed within 2 to 4 weeks after the completion of neoadjuvant therapy, with subsequent adjuvant radiotherapy or chemoradiotherapy based on risk factors after surgery. Subjects will receive Ivonescimab treatment for 14 cycles following the completion of radiotherapy.
干预措施: Becotatug Vedotin Combined with Ivonescimab (Drug)
结局指标
主要结局
pCR
时间窗: After surgery (approximately 9-10 weeks after start of study treatment)
Pathological complete response rate
次要结局
- MPR(After surgery (approximately 9-10 weeks after start of study treatment))