Penpulimab Combined With GP ± Arotinib Induction Therapy + Concurrent Chemoradiotherapy + Adjuvant Peramprizumab in Locoregionally Advanced Nasopharyngeal Carcinoma: A Phase II Clinical Trial
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 104
- 试验地点
- 1
- 主要终点
- Stage 1(Pick the Winner Study): Complete Response
研究概览
简要总结
The purpose of this study is to explore the efficacy and safety of a combination of GP chemotherapy and Penpulimab ± Anlotinib in neoadjuvant therapy combined with Penpulimab in adjuvant therapy of locoregionally advanced nasopharyngeal carcinoma patients.
详细描述
Radiotherapy combined with chemotherapy is the standard treatment method for locally advanced NPC. In the 2020 National Comprehensive Cancer Network (NCCN) guidelines, GP regimen induction chemotherapy combined with concurrent chemoradiotherapy has been established as evidence-based grade 2A.
Based on the results of phase 3 clinical trials, the addition of PD-1 monoclonal antibody to GP chemotherapy as a first-line treatment for patients with recurrent or metastatic nonkeratinizing NPC provided superior PFS, ORR and DoR than GP alone while maintaining a manageable safety profile. Therefore, the combination of PD-1 monoclonal antibody in GP induction chemotherapy may further improve the prognosis of patients with locally advanced NPC.
There is a complex interaction between tumor immune microenvironment and tumor vascular remodeling. Anti-PD-1 monoclonal antibody combined with anti-VEGF have synergistic effect and inhibit tumor growth.
Penpulimab is a new type of PD-1 monoclonal antibody. It has the characteristics of strong antigen binding and slow dissociation rate, which can maintain the antitumor activity of T cells.
Anlotinib is a multi-target tyrosine kinase inhibitor (TKI). It can effectively inhibit a variety of receptors, including vascular endothelial growth factor receptor (VEGFR), and block tumor angiogenesis more comprehensively.
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 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Voluntary participation with Written informed consent.
- •Age ≥ 18 years and ≤ 65 years, male or non-pregnant female.
- •Histologically confirmed with Nonkeratinizing carcinoma of the nasopharynx (differentiated or undifferentiated type, WHO II or III).
- •Original clinical staged as III-IVa (according to the 8th AJCC edition),exclude T3-4N0, T3N1(Only retropharyngeal lymph nodes metastasized), Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or
- •White blood cell count (WBC)≥4.0×109 /L, Hemoglobin ≥ 90g/L, Platelet count ≥100×109/L.
- •Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5×upper limit of normal (ULN),serum total bilirubin (TBIL) ≤2.0 times the upper limit of normal (ULN) .
- •Adequate renal function: creatinine clearance rate≥60 ml/min or Creatinine ≤1.5× upper limit of normal value.
排除标准
- •Patients with recurrent or metastatic nasopharyngeal carcinoma.
- •Histologically or cytologically confirmed with keratinizing squamous cell carcinoma of the nasopharynx.
- •Prior therapy with Systemic chemotherapy.
- •Women in the period of pregnancy, lactation, or reproductive without effective contraceptive measures.
- •Seropositivity for human immunodeficiency virus (HIV).
- •Known history of other malignancies (except cured basal cell carcinoma or carcinoma in situ of the cervix).
- •Prior exposure to immune checkpoint inhibitors,including anti-PD-1, anti-PD-L1, anti-CTLA-4 antibodies.
- •Patients with immunodeficiency disease or a history of organ transplantation.
- •Received large doses of glucocorticoids, anticancer monoclonal antibodies, or other immunosuppressants within 4 weeks.
- •Patients with severe dysfunction of heart, liver, lung, kidney or marrow.
- •Patients with severe, uncontrolled disease or infections.
- •Received other research drugs or in other clinical trials at the same time.
- •Refuse or fail to sign the informed consent .
- •Patients with other treatment contraindications.
- •Patients with personality or mental disorders, incapacity or limited capacity for civil conduct.
- •Hepatitis B surface antigen (HBsAg) positive and peripheral blood HBV deoxyribonucleic acid (HBV DNA) ≥1000cps/ml.
- •Patients with positive HCV antibody test will only be enrolled in this study if the PCR test for HCV RNA is negative.
研究组 & 干预措施
GP combine with Penpulimab and anlotinib neoadjuvant therapy+CCRT+Penpulimab adjuvant therapy
Patients receive neoadjuvant therapy with gemcitabine(1000mg per square meter on days 1,8) , cisplatin (80mg per square meter on day 1), penpulimab (200mg, day1), and anlotinib (10mg days 1-14) every three weeks for three cycles before radiotherapy, then followed by concurrent IMRT and cisplatin (100mg per square meter) concurrent every three weeks during radiotherapy (D1, D22, D43 of RT) ,then followed by adjuvant therapy with penpulimab (200mg) every three weeks for a maximum of nine cycles after radiotherapy.
干预措施: GP+Penpulimab+Anlotinib (Drug)
GP combine with Penpulimab neoadjuvant therapy+CCRT+Penpulimab adjuvant therapy
Patients receive neoadjuvant therapy with gemcitabine(1000mg per square meter on days 1,8) , cisplatin (80mg per square meter on day 1), penpulimab (200mg, day1) every three weeks for three cycles before radiotherapy, then followed by concurrent IMRT and cisplatin (100mg per square meter) concurrent every three weeks during radiotherapy (D1, D22, D43 of RT) ,then followed by adjuvant therapy with penpulimab (200mg) every three weeks for a maximum of nine cycles after radiotherapy.
干预措施: GP+Penpulimab (Drug)
结局指标
主要结局
Stage 1(Pick the Winner Study): Complete Response
时间窗: 9 weeks
The proportion of patients who had a complete response was defined as those with all pathological cervical lymph nodes being less than 10 mm in the short axis and no unequivocal soft tissue mass in the local region. Disease response was evaluatedby by the Investigator using Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST 1.1) 95% confidence intervals (CIs) were calculated using the Clopper Pearson method
Stage 2 (Cohort Expansion Study): Failure-free survival (FFS)
时间窗: 3 years
Defined as the time from registration to documented local or regional relapse, distant metastasis, or death from any cause, whichever occurred first.
次要结局
- Locoregional failure-free survival (LRRFS)(3 years)
- Incidence rate of adverse events (AEs)(3 years)
- Objective Response Rate (ORR)(9 weeks)
- Overall survival (OS)(3 years)
- Distant metastasis-free survival (DMFS)(3 years)
研究者
Hai-Qiang Mai,MD,PhD
Ph.D
Sun Yat-sen University