The purpose of this study is to see the safety and efficient of neoantigen reactive T cells (NRTs) combined with programmed cell death-1(PD-1) inhibitor(SHR-1210)in the treatment of Chinese patients with advanced refractory solid tumors.
The tumor-specific "none-self" immunogenic neoantigens encoded by either viral genes or somatic mutation genes, possess the potential to induce specific anti-cancer immunity, including cellular and humoral immune responses. Today, numerous clinical trials demonstrate that although these "none-self" antigens initiate the antigen-specific immunoglobulin G antibodies and cluster of differentiation 4(CD4)+/cluster of differentiation 8(CD8)+T-cells response, not all of them show a clinical benefit in the response rate, progression-free survival or overall survival.Immune tolerance induced by PD-1 or programmed cell death-ligand1( PD-L1)maybe play a vital role for these negative outcomes.Personalized cell therapy plus checkpoint inhibitors maybe own a breakthrough in the treatment of those malignant diseases without standard options.Our center has successfully established a new method for preparing personalized neoantigen reactive T cells(NRTS) for adoptive cell therapy(ACT). Today, we will carry out a single center single arm clinical prospective study of NRTs combined with PD-1 inhibitor(SHR-1210) for the treatment of Chinese patients with advanced refractory solid tumors. Participants are assigned to receive 4 circles of cell therapy,and prior to each cycle's immunocytes treatment,preconditional chemotherapy and SHR-1210 will be carried out, and IL-2 continuous intravenous infusion(CIV) will also be given for 5 consecutive days after each time's cell infusion. The safety and clinical response rate(RR) are evaluated. Biomarkers and immunological markers are also monitored.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
40
Neoantigen Reactive T Cells in an expected volume of 100 milliliter(mL) will be given by intravenous injection over 2-10 minutes through either a peripheral or a central line.
SHR-1210 200mg will be administered as an intravenous infusion over 60 minutes.
Fludarabine(FLU) 30mg/m2/d×3d,3 days prior to each NRTs infusion as preconditional chemotherapy.
The Comprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing University and Clinical Cancer Institute of Nanjing University
Nanjing, Jiangsu, China
RECRUITINGNumber of participants with Adverse Events
using Common Terminology Criteria for Adverse Events (CTCAE v4.0) in patients
Time frame: up to 6 months
Response Rate
Response Rate(RR) will be evaluated according Response Evaluation Criteria in Solid Tumors
Time frame: At 3, 6 and 12 months
Progression free survival (PFS)
the duration of progression free survival is measured from the time of treatment to the first date that recurrent or progressive disease or for any reason of death is objectively documented.
Time frame: At 6,9 and 12 months
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Cyclophosphamide(CTX) 300mg/m2/d×3d,3 days prior to each NRTs infusion as preconditional chemotherapy.
Interleukin-2(IL-2)will be continuous intravenous infused since the first day of the cell infusion for 5 consecutive days, 4000,000 international unit per day.