Efficacy and Safety of Scipibaimab Combined With Tislelizumab in the Treatment of Patients With Recurrent and Metastatic Nasopharyngeal Carcinoma Who Have Failed First-line Treatment: a Multicenter, Single-arm, Non-randomized, Open-label Phase II Clinical Study
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 37
- 试验地点
- 1
- 主要终点
- Objective response rate
研究概览
简要总结
This study aims to explore the efficacy and safety of scipibaimab combined with tislelizumab in patients with recurrent or metastatic nasopharyngeal carcinoma who have progressed after first-line therapy.
详细描述
In the immunotherapy era, patients with recurrent/metastatic nasopharyngeal carcinoma who progress after both platinum-based chemotherapy and PD-1 blockade lack further standard options. IL-4Rα inhibition can overcome PD-1 resistance by re-activating CD8+ T cells; combining scipibaimab (anti-IL-4Rα) with tislelizumab (anti-PD-1) has shown additive activity without overlapping toxicity. This trial will assess the efficacy and safety of the combination in patients who have failed prior platinum and PD-1 therapy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •1. Histologically or cytologically confirmed with recurrent or metastatic nasopharyngeal carcinoma which is not amenable to curative treatment with surgery and/or radiation therapy.
- •2. Age ≥ 18 years and ≤ 75 years, both genders.
- •3. Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or
- •4. Life expectancy of at least 3 months.
- •5. Have failed for first-line platinum-based chemotherapy.
- •6. Have failed for prior treatment with PD-1 antagonists +/- chemotherapy.
- •7. Patients must have at least 1 lesion that is measurable using RECIST v1.1 criteria.
- •8. Patients must have adequate organ function (without blood transfusion, without growth factor or blood components support within 14 days before enrollment) as determined by: Absolute neutrophil count (ANC) ≥1.5×109/L; Platelet count ≥ 75×109/L; Hemoglobin ≥ 9 g/dL; serum total bilirubin (TBIL) ≤1.5 times the upper limit of normal (ULN); alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5×upper limit of normal (ULN), (for subjects with liver metastases, TBIL ≤3×ULN ; ALT and AST≤5×ULN); Creatinine ≤1.5×ULN or creatinine clearance rate≥50 ml/min (Cockcroft-Gault formula); serum albumin ≥28 g/L; Thyroid-stimulating hormone (TSH) levels ≤1×ULN (however, patients with free Triiodothyronine [FT3] or free Thyroxine [FT4] levels ≤1× ULN may be enrolled); INR, APTT≤1.5 x ULN.
- •9. All women with fertility potential must undergo a urine or serum pregnancy test during screening and the results are negative.
- •10. Written informed consent.
排除标准
- •1.Known history of hypersensitivity to any components of the Tislelizumab formulation, or other monoclonal antibody.
- •2.Prior therapy with any anti-interleukin-4 receptor α (IL-4Rα) monoclonal antibody, anti-IgE monoclonal antibody, or other monoclonal antibodies/biological agents.
- •3.There was a history of severe bleeding, and any bleeding events with a serious grade of 3 or more in CTCAE5.0 occurred within 4 weeks before screening.
- •4.Before treatment, MRI showed that the tumor may have invaded important blood vessels (such as enclosing the internal carotid artery / vein), nasopharyngeal necrosis, or researchers have determined that the tumor is highly likely to invade important blood vessels and cause fatal massive bleeding during treatment.
- •5.Patients with abnormal blood coagulation and bleeding tendency (14 days before signing informed consent: INR is within the normal range without anticoagulant); patients treated with anticoagulants or vitamin K antagonists such as warfarin, heparin or their analogues. On the premise that the INR < 1.5, low-dose warfarin (1mg orally, once a day) or low-dose aspirin (daily dose not more than 100mg) is allowed for preventive purposes.
- •6.Arteriovenous thrombosis occurred within one year before screening, such as cerebrovascular accident (including temporary ischemic attack), deep venous thrombosis (except venous thrombosis caused by intravenous catheterization due to early chemotherapy) and pulmonary embolism.
- •7. Prior malignancy active within the previous 5 years except for locally curable cancers that have been apparently cured, such as basal cell skin cancer or carcinoma in situ of the cervix.
- •8. Join another clinical study at the same time, received any research drug within 4 weeks before the first administration of the drug.
- •9. Patients with any active autoimmune disease or a documented history of autoimmune disease such as pneumonia, colitis, hepatitis, nephritis, hyperthyroidism or hypothyroidism;
- •10. Concurrent medical condition requiring the use of immunosuppressive medications, or immunosuppressive doses of systemic or absorbable topical corticosteroids. Doses > 10 mg/day prednisone or equivalent are prohibited within 2 weeks before study drug administration.
- •11. History of immunodeficiency including seropositivity for human immunodeficiency virus (HIV), or other acquired or congenital immune-deficient disease.
- •12. Be known to have active tuberculosis.
- •13. Hepatitis B virus (HBV) >2000 IU/ml or DNA ≥ 1×10^4/ml; or hepatitis C virus (HCV) RNA ≥ 1×10^3/ml).
- •14. Has an active infection requiring systemic therapy.
- •15. Has known active central nervous system metastases.
- •16. Severe, uncontrolled angiocardiopathy (heart failure > class II NYHA, unstable angina, myocardial infarction within past 1 year, supraventricular or ventricular arrhythmia which need medical intervention, or QT interval male ≥ 450 ms, female ≥ 470 ms.).
- •17. Have been vaccinated with anti-tumor vaccines or have been vaccinated with live vaccines within 4 weeks before screening.
- •18. Pregnant or nursing.
- •19. Underlying medical condition that, in the Investigator's opinion, would increase the risks of study drug administration or obscure the interpretation of toxicity determination or adverse events.
研究组 & 干预措施
Scipibaimab combined with Tislelizumab
Patients with recurrent or metastatic nasopharyngeal carcinoma who have progressed after first-line platinum-based chemotherapy plus PD-1 inhibition will receive scipibaimab 300 mg subcutaneous and tislelizumab 200 mg intravenous every 3 weeks until disease progression, unacceptable toxicity, or completion of 2-year treatment window.
干预措施: Tislelizumab (Drug)
Scipibaimab combined with Tislelizumab
Patients with recurrent or metastatic nasopharyngeal carcinoma who have progressed after first-line platinum-based chemotherapy plus PD-1 inhibition will receive scipibaimab 300 mg subcutaneous and tislelizumab 200 mg intravenous every 3 weeks until disease progression, unacceptable toxicity, or completion of 2-year treatment window.
干预措施: Scipibaimab (Drug)
结局指标
主要结局
Objective response rate
时间窗: 2 years
An objective response is defined as either a confirmed CR or a PR, as determined by the investigator using Response Evaluation Criteria in Solid Tumors (RECIST1.1) from the National Cancer Institute (NCI)
次要结局
- Disease control rate(2 years)
- Duration of response(2 years)
- Progression-free survival rate(2 years)
- Overall survival rate(2 years)
- Incidence rate of adverse events (AEs)(2 years)
研究者
Hai-Qiang Mai,MD,PhD
Director of the Department of Nasopharyngeal Carcinoma
Sun Yat-sen University