Clinical Study on the Safety and Efficacy of GK01 Autologous Tumor-reactive T Cells (TRT) in Patients With Advanced Solid Tumors
This trial plans to enroll many patients with advanced solid tumors to complete GK01 cell transfusion, including but not limited to advanced gastric cancer, esophageal cancer, cervical cancer, triple-negative breast cancer, and non-small cell lung cancer. For patients with advanced solid tumors eligible for inclusion, autologous tumor-reactive T cells (experimental drug GK01) were cultured and prepared, and a certain dose of GK01 cells was given according to the cell transfusion plan, and the safety and tolerability of the patients after transfusion were observed. Exploratory evaluation of pharmacokinetic/pharmacodynamic profiles following reinfusion and initial evaluation of efficacy of investigational drug GK01 cells according to RECIST 1.1 criteria.
• Participants who meet all of the following criteria are eligible for admission to the study:
‣ 18≤ age ≤75 years old, male or female;
⁃ Patients with incurable advanced gastric cancer, esophageal cancer, cervical cancer, triple-negative breast cancer, non-small cell lung cancer, and other malignancies who have failed standard treatment (standard treatment failure is defined as those treated according to the 2022 CSCO Guidelines and whose tumor efficacy is assessed as disease progression (PD) or tumor recurrence or inability to tolerate existing treatment options);
⁃ There are tumor tissues or cancerous exudative thoracoabdominal fluid that can be used to isolate TRTs: the total volume of the solid tissue taken must be \> 0.5cm3 or the weight must be \>0.5g, the cancerous exudative thoracoabdominal fluid taken should contain at least 5×10\^8 total cells, and the lesions taken have not been treated with oncolytic virus.
⁃ There is at least one measurable lesion (according to RECIST1.1 criteria) even after TRTs sampling/puncture biopsy;
⁃ ECOG score 0-1;
⁃ The expected survival period is greater than 3 months;
⁃ Sufficient hematology and end-organ function, as defined by the following laboratory test results, should be completed within 14 days prior to TRTs tumor tissue collection:
• Blood routine: white blood cell count ≥2.5×10\^9/L; Absolute neutrophil count (ANC) ≥1.5×10\^9/L; Absolute lymphocyte count (ALC) ≥1.0×10\^9/L; Platelet (PLT) ≥80×10\^9/L; Hemoglobin (HGB) ≥90g/L;
∙ Coagulation function: International standardized ratio of prothrombin time (INR) ≤1.5×ULN; Partial prothrombin time (APTT) ≤1.5×ULN, unless anticoagulant therapy has been received within the previous 7 days;
∙ Renal function: serum creatinine ≤1.5mg/dL (or 132.6μmol/L) or creatinine clearance ≥60mL/ min;
∙ Liver function: aspartate aminotransferase (AST/SGOT) ≤3×ULN; Alanine transaminase (ALT/SGPT) ≤3×ULN; Total bilirubin (TBIL) ≤1.5×ULN; Note: In patients with liver metastasis or primary liver tumor, aspartate and alanine aminotransferase should be ≤5×ULN; For patients with a history of Gilbert syndrome or suspected Gilbert syndrome, total bilirubin (TBIL) should be ≤3×ULN;
∙ Urine routine: urinary protein \<2+, or 24-hour urinary protein quantity \<1g;
∙ Left ventricular ejection fraction (LVEF) ≥50% by echocardiography;
∙ Pulmonary function tests with FEV1\>60% or FEV1/FVC\>0.7;
∙ Blood oxygen saturation ≥ 93%.
⁃ Women of childbearing age who have a negative urine pregnancy test during screening and baseline and agree to use highly effective contraception for at least 1 year after the infusion; Male subjects whose partners are fertile must agree to use effective contraceptive methods and refrain from sperm donation for at least 1 year after the infusion;
⁃ No absolute or relative contraindications to surgery or puncture;
‣ Any treatment for malignant tumors, including radiotherapy, chemotherapy, endocrine therapy, targeted therapy, tumor embolization, or Chinese medicine/herbal therapy with anti-tumor indications, must be discontinued 7 days before TRT sampling;
‣ Sign a written informed consent (ICF) voluntarily, and have good compliance with the protocol requirements for visits or planned visits and other relevant research procedures.