Phase Ib Clinical Study on the Safety, the Tolerability, the Pharmacokinetics and the Efficacy of ScTIL Injection (Gene Modified Tumor Infiltrating Lymphocytes) Alone and in Combination With B Lymphocyte Adjuvant in the Treatment of Digestive System Malignant Solid Tumors

Brief summary public domain (ClinicalTrials.gov)

This is an open-lable, single-arm, single-dose escalation and multiple-dose extention clinical study of cell therapy designed to observe and evaluate the tolerance, the pharmacokinetic characteristics, the safety and the efficacy of ScTIL210 injection alone and in combination with B lymphocytes adjuvant in the treatment of digestive system malignant solid tumors.

Detailed description public domain (ClinicalTrials.gov)

This study consists of two phases: the first phase will be the dose exploration phase (Phase I), followed by the dose extension phase (Phase II). In phase I, 3 subjects are enrolled for 1st treatment group, starting with single dose of ScTIL injection of 5x10\^9 alone. If there is no dose limiting toxicity (DLT) observed, 3 subjects are enrolled into treatment groups successively in sequential order of: 1) Group 2: ScTIL1.5x10\^10 alone; 2) Group 3: ScTIL 5x10\^9 plus B lymphocytes adjuvant 5x10\^9; and 3) Gorup 4: ScTIL1.5x10\^10 plus B lymphocytes adjuvant 1.5x10\^10. Preconditioning chemotherapy will be performed to subjects of 3rd and 4th treatment group. Fludarabine 25mg/m2/day and cyclophosphamide 250mg/m2/day will be intravenously administered at 5 and 4 days (Day -5 and Day -4) before reinfusion of ScTIL and B lymphocyte adjuvant at Day 0. After the completion of ScTIL reinfusion for first subject of the 1st dose group, the subject will be observed for no less than one week. If no serious toxic and adverse events occurres, ScTIL reinfusion for the second and third subjects will be performed. If no DLT occurres by the 14th days after completion of reinfusion for the 3rd subject, The study will move to the next treatment group. If 1/3 of enrolled subjects have DLT, another 3 subjects will be enrolled. In any of the dose groups, if ≤1/6 subjects have DLT, subject enrollment for the next treatment group will start. If DLT occurs in ≥2/6 of subjects, the number of subjects in the previous dose group shall be reviewed. If there were only 3 subjects, 3 more subjects will be enrolled. If DLT occurs in ≤1/6 subjects, the dose will be defined as the maximum tolerable dose (MTD), and the dose escalation phase of the study will be completed. If DLT occurs in ≥2/6 subjects in the first dose group, a dose reduction exploration will be performed or the study will be terminated upon decision made by the Safety Committee. A independent third party safety audit committee (consists of no clinical study participants) will conduct safety audit 14 days after the first ScTIL reinfusion of the third subject of the 1st treatment group. In phase II, If no dose limiting toxicity event occurred after the completion of treatment in each of the 4 groups. Researcher will decide to select 2-4 dose groups for dose extention study and will enroll 5-10 subjects for each group.

Intervention public domain (ClinicalTrials.gov)

Biological: ScTIL injection. Peripheral blood mononuclear cells (PBMCs) obtained via apheresis are used for cell preparation. PD-1 positive T cells are isolated from PBMCs, are transduced with lentivirus loaded with "enhanced receptor" and "superamplification factor", and cell number are amplified. The obtained ScTIL is used for one-time intravenous infusion.

Intervention public domain (ClinicalTrials.gov)

Biological: ScTIL injection and B lymphocytes adjuvant. B lymphocyte are also isolated from PBMCs. If the percentage of subject's B lymphocyte in total lymphocytes is > 5%, the autologous B lymphocyte adjuvant will be prepared. If this percentage is ≤ 5%, PBMCs will be collected from haploidentical donor of the subject via apheresis, and B lymphocyte will be isolated for preparation of allogeneic B lymphocyte adjuvant.

Arm public domain (ClinicalTrials.gov)

ScTIL injection (experimental): This trial is designed single arm. All the subjects enrolled will receive the experimental intervention: ScTIL210 injection alone or with B lymphocytes adjuvant.