An Open-label, Phase I Study to Assess the Safety and Clinical Activity of Multiple Doses of NKR-2, Administered Concurrently With the Neoadjuvant FOLFOX Treatment in Patients With Potentially Resectable Liver Metastases From Colorectal Cancer
试验速览
- 阶段
- 1 期
- 入组人数
- 36
- 试验地点
- 8
- 主要终点
- The objective response rate (ORR) before resection as measured by RECIST (version 1.1)
研究概览
简要总结
SHRINK (Standard cHemotherapy Regimen and Immunotherapy with NKR-2) is an open-label Phase I study to assess the safety and clinical activity of multiple administrations of autologous NKR-2 cells administered concurrently with a standard chemotherapy treatment (FOLFOX) in potentially resectable liver metastases from colorectal cancer.
The trial will test three dose levels. At each dose, the patients will receive three successive administrations, two weeks apart, NKR-2 cells. The study will enroll up to 36 patients (dose escalation and expansion phases).
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 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
- •Men or women ≥ 18 years old at the time of signing the ICF
- •Patients with histologically proven colorectal adenocarcinoma with potentially resectable liver metastases,
- •No previous chemotherapy for metastatic CRC,
- •The patient is due to receive first-line metastatic chemotherapy regimen with FOLFOX as a neoadjuvant
- •The patient must have an ECOG performance status 0 or 1
- •The patient must have sufficient bone marrow reserve, hepatic and renal functions
- •Detailed disease specific criteria exist and can be discussed with contacts listed below
排除标准
- •Patients who have received another cancer therapy within 2 weeks before the planned day for the apheresis
- •Patients who receive or are planned to receive any other investigational product within the 3 weeks before the planned day for the first NKR-2 administration
- •Patients who are planned to receive concurrent growth factor, systemic steroid or other immunosuppressive therapy or cytotoxic agent, other than the treatment authorized per protocol
- •Patients who underwent major surgery within 4 weeks before the planned day for the first treatment
- •Patients with uncontrolled intercurrent illness or serious uncontrolled medical disorder
- •Patients who have received a live vaccine within 6 weeks prior to the planned day for the first NKR 2 administration
- •Patients with a family history of congenital or hereditary immunodeficiency
- •Patients with history of any autoimmune disease
结局指标
主要结局
The objective response rate (ORR) before resection as measured by RECIST (version 1.1)
时间窗: up to resection (up to day 99 to day 126)
The objective response rate (ORR) is defined as the sum of the proportions of patients achieving CR or PR. The occurrence of ORR before resection will be reported.
The occurrence of Dose Limiting Toxicities (DLT) in all patients during the study treatment until 14 days after the first NKR-2 study treatment administration
时间窗: up to resection (up to day 99 to day 126)
DLT refers to any Grade 3 or higher toxicity or any Grade 2 or higher autoimmune toxicity that is experienced during treatment and within 14 days following the first NKR-2 dose, is new and at least possibly related to NKR-2 study treatment administered concurrently with chemotherapy
次要结局
- The resection rate(resection (day 99 to day 126))
- The disease-free survival (DFS) or progression-free survival (PFS)(through study completion (up to month 28))
- The occurrence of AEs and SAEs and any toxicity corresponding to DLT definition during the study treatment until resection visit(up to resection (up to day 99 to day 126))
- The occurrence of surgery complications and the wound healing status until 60 days after resection visit(until 60 days after resection)
- The clinical benefit rate (CBR) before resection(up to resection (up to day 99 to day 126))
- The occurrence of mixed response (MR) before resection(up to resection (up to day 99 to day 126))
- The event-free survival (EFS)(through study completion (up to month 28))
- The overall survival (OS)(through study completion (up to month 28))
- The occurrence of pathological response at surgery(resection (day 99 to day 126))