A Clinical Study to Evaluate the Safety and Efficacy of Autologous Tumor Infiltrating Lymphocytes Injection in Patients With Advanced Malignant Solid Tumors
Overview
- Phase
- Early Phase 1
- Intervention
- Tumor Infiltrating Lymphocytes (TIL)
- Conditions
- Advanced Solid Tumors
- Sponsor
- Shanghai Juncell Therapeutics
- Enrollment
- 20
- Locations
- 1
- Primary Endpoint
- Adverse Events(AE)
- Status
- Recruiting
- Last Updated
- 4 months ago
Overview
Brief Summary
This study is to investigate the safety and efficacy of tumor infiltrating lymphocyte (TIL) therapy in patients with Advanced malignant solid tumors.Autologous TILs are expanded from tumor resections or biopsies and infused i.v. into the patient after NMA lymphodepletion treatment with hydroxychloroquine(600mg,single-dose) and cyclophosphamide.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Age: 18 years to 75 years;
- •Histologically diagnosed as primary/relapsed/metastasized malignant tumors;
- •Expected life-span more than 3 months;
- •Karnofsky≥60% or ECOG score 0-2;
- •Test subjects have failed standard treatment regimens, or there are no standard treatment regimens available.
- •Test subjects must have tumor regions eligible for biopsy or resection, or malignant body fluid where TILs can be isolated;
- •At least 1 evaluable tumor lesion;
- •Hematology and Chemistry（within 7 days prior to enrollment）:
- •Absolute count of white blood cells≥2.5×10\^9/L;
- •Absolute count of neutropils≥1.5×10\^9/L;
Exclusion Criteria
- •Need glucocorticoid treatment, and daily dose of Prednisone greater than 15mg (or equivalent doses of hormones) or outoimmune diseases requiring immunomodulatory treatment;
- •Forced expiratory volume in one second (FEV1) less than 2L, diffusing capacity of the lung for carbon monoxide (DLCO) (calibrated) less than 40%;
- •Significant cardiovascular anomalies according to any of the following definition: New York Heart Association (NYHA) Grade III or IV congestive heart failure, clinically significant low blood pressure, uncontrollable symptomatic coronary artery diseases, or ejection fraction less than 35%; Severe cardiac rhythm and conduction anomaly, such as ventricular arrhythmia requiring clinical intervention, second-third degree atrio-ventricular conductive block, etc.
- •Human immunodeficiency virus (HIV) infection or anti-HIV antibody positive, active HBV or HCV infection (HBsAg positive and/or anti-HCV positive), syphilis infection or Treponema pallidum antibody positive;
- •Severe physical or mental diseases;
- •Have a systemic active infection requiring treatment, or have positive blood cultures(or imaging evidence of infection);
- •Having been treated within a month or being treated now with other medicines, or other biologic therapy, chemo-or radiotherapy;
- •History of allergy to chemical compound consisting of chemical and biologic substances resembling cell therapy;
- •Having received immunotherapy and developed irAE level greater than Level 3;
- •Previous anti-tumor treatment AE did not return to CTCAE5.0 version grade 1 or below (toxicity considered by the investigator as non-safety concerns like alopecia excluded);
Arms & Interventions
Tumor Infiltrating Lymphocytes
1x10\^9-5x10\^10 in vitro expanded autologous TILs will be infused i.v. to patients with advanced solid tumors after NMA lymphodepletion treatment with hydroxychloroquine(600mg,single-dose) and cyclophosphamide.
Intervention: Tumor Infiltrating Lymphocytes (TIL)
Outcomes
Primary Outcomes
Adverse Events(AE)
Time Frame: 6 month
To characterize the safety profile of GC101 TIL in patients with recurrent, metastatic, or persistent solid tumor as assessed by incidence of adverse events.
Objective Response Rate (ORR)
Time Frame: Up to 36 months
Proportion of patients with response per Response Evaluation Criteria in Solid Tumors (RECIST v1.1): ORR (proportion of patients) = # with CR + # with PR / # with CR + # with PR + # with SD + # with PD. ( Except baseline evaluation within 28 days before GC101 TIL infusion，PET/CT scan will be performed at 6 weeks after TIL infusion, and than every 6 weeks for 6 months, and then every 6 months after that for up to 3 years)
Secondary Outcomes
- Disease Control Rate (DCR）(Up to 36 months)
- Duration of Response (DOR)(Up to 36 months)
- Progression-Free Survival (PFS)(Up to 36 months)
- Overall Survival (OS)(Up to 36 months)