A Single-arm, Open Clinical Trial of Efficacy and Safety of Tislelizumab in Combination With Disitamab-vedotin as Neoadjuvant Therapy for HER2-positive High-risk Upper Tract Urothelial Carcinoma (UTUC)
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 21
- 试验地点
- 1
- 主要终点
- pathological complete response (pCR)
研究概览
简要总结
Neoadjuvant chemotherapy treatment can be used for specific UTUC patients, especially for highly staged and/or grade tumors, such as kidneys with potentially decreased renal function after RNU. Neoadjuvant therapy is a series of treatments administered preoperatively for UTUC, mainly chemotherapy, and in recent years, novel therapies of immunotherapy have emerged. Since conventional cisplatin neoadjuvant regimens also require high preoperative renal function, neoadjuvant therapy regimens such as immunotherapy provide more effective and feasible treatments for patients who are intolerant to current cisplatin chemotherapy regimens. The aim of this study was to explore the efficacy and safety of the combination of disitamab vedotin, a human epidermal growth factor receptor-2 (HER-2) targeted ADC, and tislelizumab, a humanised PD-1 ICIs, as neoadjuvant treatment for non-metastatic, high-risk, HER-2 expressing UTUC. In our study, patients enrolled will receive neoadjuvant tislelizumab plus disitamab-vedotin therapy followed by radical nephroureterectomy (RNU), distal ureterectomy (DU) or ureteroscopic ablation (UA) .
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
- •Radiographically(CT, MRI or PET-CT, etc.) and histologically confirmed diagnosis of localized HER-2 expressing upper urothelial carcinoma( (cT1-4N0-2M0, HER-2 immunohistochemistry (IHC) ≥ 1+); high risk disease (according to EAU Guidelines for UTUC); planning to receive radical nephroureterectomy (RNU), distal ureterectomy (DU) or ureteroscopic ablation (UA).
- •Male or female aged 18 years and above;
- •Expected survival time greater than 12 weeks;
- •An ECOG status score of 0-2;
- •Agree to provide specimens of blood, urine, and tissue examination (for detection of MRD, PD-L1 expression, HER2 expression, tumor mutation load, immunohistochemistry, DNA and RNA detection, etc.);
- •The level of organ function must meet the following requirements:
- •hematological indicators: absolute neutrophil count ≥ 1.5 × 10^9/L, platelet count ≥ 80 × 10^9/L, hemoglobin ≥ 6.0 g/dL (can be maintained by symptomatic treatment)
- •hepatic function: total bilirubin ≤ 1.5 times the upper limit of normal, and glutathione and glutamic oxalacetic transaminase ≤ 2.5 times the upper limit of normal;
- •renal function: GFR ≥ 15 ml/min;
- •Subjects voluntarily joined the study, signed an informed consent form, were compliant, and cooperated with the follow-up.
排除标准
- •Live attenuated vaccines, other than COVID-19 vaccine, received within 4 weeks prior to treatment or scheduled to be received during the study period
- •Active, known or suspected autoimmune disease;
- •Known history of primary immunodeficiency;
- •Known history of allogeneic organ transplantation and allogeneic hematopoietic stem cell transplantation
- •Female patients who are pregnant or breastfeeding
- •Untreated acute or chronic active hepatitis B or C infection. Patients who are receiving antiviral therapy with monitoring of viral copy number and are eligible for enrollment as determined by the physician on an individual patient basis;
- •Previous use of immunosuppressive drugs, excluding nasal spray and inhaled corticosteroids or physiologic doses of systemic steroids (i.e., no more than 10 mg/day prednisolone or equivalent pharmacologic physiologic doses of other corticosteroids), within 4 weeks prior to initiation of therapy
- •Known or suspected allergy history to tislelizumab and disitamab vedotin.
- •With a clear history of active tuberculosis.
- •Prior PD-1/PD-L1/CTLA-4 antibody or other immunotherapy;
- •Those who are participating in other clinical studies
- •Men of reproductive potential or women with the potential to become pregnant who are not using reliable contraception
- •Uncontrolled co-morbidities, including but not limited to
- •HIV-infected individuals (HIV-positive);
- •Severe infections that are active or poorly controlled clinically (including patients in the period of neocoronavirus infection)
- •Evidence of the presence of severe or uncontrolled systemic disease (e.g., severe psychiatric, neurological disease, epilepsy or dementia, unstable or uncompensated respiratory, cardiovascular, hepatic or renal disease, uncontrolled hypertension [i.e., defined as greater than or equal to CTCAE grade 2 hypertension despite medication]).
研究组 & 干预措施
tislelizumab+disitamab-vedotin
干预措施: tislelizumab+disitamab-vedotin (Drug)
结局指标
主要结局
pathological complete response (pCR)
时间窗: 3 months
no residual tumor was detected in the specimen from RNU/DU by pathological examination
次要结局
- Treatment-related adverse events(From treatment initiation to the end of treatment at 90 days.)
- overall survival(5 years since treatment initiation.)
- recurrence-free survival(5 years since treatment initiation.)
- imaging complete response(3 months.)
- imaging partial response(3 months.)
- imaging progressive disease(3 months.)
- imaging stable disease(3 months.)