A Phase 2, Open Label, Single Arm Clinical Trial of Neoadjuvant Nivolumab and Relatlimab in Stage I To III Resectable Merkel Cell Carcinoma
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 20
- 试验地点
- 2
- 主要终点
- Pathological complete response rate
研究概览
简要总结
The goal of this clinical trial is to test neoadjuvant dual immunotherapy in Merkel cell carcinoma with the aim to improve recurrence-free survival
详细描述
This is a phase 2, open label, single cohort, single centre, clinical trial of neoadjuvant immunotherapy with dual inhibition of PD-1 and LAG-3 immune checkpoint pathways. The hypothesis is that neoadjuvant therapy produces a higher pathological response rate (pCR) and a longer recurrence-free survival in a cohort of treatment-naïve patients with resectable stage I (≥10 mm) to stage III Merkel cell carcinoma compared to neoadjuvant nivolumab monotherapy in Checkmate 358 (n=123, NCT02488759, historical control).
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Aged ≥ 18 years
- •Written consent
- •Histologically confirmed, resectable Merkel cell carcinoma with AJCC (8th ed) clinical or pathological stage I (≥ 10 mm), IIA, or IIB or III disease
- •In-transit metastases are permitted if they are completely resectable
- •Measurable disease according to RECIST 1.1 criteria
- •Previous radiotherapy permitted if there is RECIST-measurable progression of disease since the completion of radiotherapy
- •At least one of either, archival tissue from a primary or nodal MCC lesion (if applicable) for the current diagnosis and/or a newly obtained core biopsy of a lesion which has not been previously irradiated.
- •Adequate organ function on blood pathology
- •Life expectancy >12 months
- •Female patients to use effective contraception during study treatment and for 5 months after last dose.
排除标准
- •Clinical, radiographic or pathological evidence of distant metastases
- •Contraindication to nivolumab and / or relatlimab
- •Prior anti-PD-1, CTLA-4, PDL-1 or LAG 3 antibody exposure, or an agent directed to another stimulatory or co-inhibitory T-cell receptor for any disease or any chemotherapy or experimental local or systemic drug treatment
- •Active autoimmune disease or requirement for chronic steroid therapy other than hormone replacement therapy
- •A diagnosis of immunodeficiency or chronic steroid therapy >10 mg OD prednisone or equivalent
- •Additional malignancy active within past 3 years; patients with chronic lymphocytic leukaemia can be included in this study.
- •Uncontrolled cardiovascular disease or history of myocarditis
- •Has had an allogenic tissue/solid organ transplant
- •Troponin T (TnT) or I (TnI) >2 × institutional ULN
- •Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis or current interstitial lung disease
- •Has an active infection requiring systemic therapy
- •Active Hepatitis B (defined as Hepatitis B surface antigen [HBsAg] reactive) or Hepatitis C virus (defined as HCV RNA [qualitative] is detected) infection.
- •Pregnant or breast feeding females
- •Concurrent medical or social conditions that may prevent the patient attending assessments or procedures per schedule
研究组 & 干预措施
Neoadjuvant Treatment
Nivolumab and relatlimab will be administered in a fixed dose combination (FDC). The FDC product contains nivolumab and relatlimab in a protein-mass ratio of 3:1 (nivolumab 240 mg and relatlimab 80 mg): in a 20 mL concentrate solution per single vial. The dose and dosing regimen for this study is nivolumab 480 mg and relatlimab 160 mg - 2 vials per infusion. This was primarily based on the observed benefit/risk profile observed in metastatic melanoma patients from Study CA224-020 pharmacokinetics (PK), pharmacodynamics, and extensive nivolumab monotherapy clinical experience. In addition, the Phase 2/3 Study CA224-047 established this dose as active in unresectable and metastatic melanoma.
This study is open label and single arm, with all patients scheduled to receive two doses of nivolumab and relatlimab FDC prior to surgery on days 1 and 29.
干预措施: Nivolumab 240 mg / Relatlimab 80 mg in a fixed dose combination (Drug)
结局指标
主要结局
Pathological complete response rate
时间窗: Week 6
Proportion of patients with a pathological complete response, as determined on the week 6 surgical specimen using the guidelines published by the International Neoadjuvant Melanoma Consortium: Complete pathological response (pCR) = 0% viable tumour cells in the surgical specimen
次要结局
- Overall survival rate(10 years)
- Pathological non-complete response rate to neoadjuvant immunotherapy(Week 6)
- Toxicity and tolerability of neoadjuvant immunotherapy and surgery(Week 24)
- Objective response rate to neoadjuvant immunotherapy(Week 6)
- Metabolic response rate to neoadjuvant immunotherapy(Week 6)
- Recurrence-free survival(10 years)
- Disease progression rate(Week 6)
- Patient reported quality of life(1 year)
- Study treatment completion rate(Week 8)
- Event-free survival (EFS) rate(10 years)
- Toxicity and tolerability of neoadjuvant immunotherapy(Week 24)
- Surgical-related adverse events(12 weeks)