NewishT Cell Therapy for HCC With High Risk of Recurrence After Radical Resection

• Status: Recruiting
• Trial end date: 2024-06-30
• Target enrollment: 0
• Participant gender: All

Summary

This is a single-arm, open label, multi-center Phase 1 clinical study to evaluate the safety and efficacy of autologous memory lymphocyte therapy (NewishT) in patients with hepatocellular carcinoma at high risk of recurrence after radical resection.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Newish Technology (Beijing) Co., Ltd.
• Collaborator: Cancer Institute and Hospital, Chinese Academy of Medical Sciences

Criteria

Inclusion Criteria:

1. 18≤ age ≤75 years, no gender limitation;

2. Primary hepatocellular carcinoma (HCC) confirmed by histopathological examination;

3. Serological tests were positive for HBsAg or HBV DNA, and patients with active virus were willing to receive anti-HBV therapy during the study period;

4. Barcelona Clinic liver cancer (BCLC) with clinical stage A/B;

5. Radical hepatocellular carcinoma surgery (laparotomy, laparoscopic surgery, ablation, robot-assisted surgery) was performed within 12 weeks before blood collection for the first preparation of NewishT; The interval between clinical stage determination of BCLC HCC and radical resection should not exceed 12 weeks.

6. No residual tumor was found in liver during image examination within 4 weeks before blood collection for the first NewishT preparation; No lymph node metastasis, no extrahepatic metastasis;

7. Have not received systematic anti-tumor therapy for liver cancer (including chemotherapy, molecular targeted therapy, biological immunotherapy);

8. Patients undergoing radical surgery should meet the intraoperative judgment criteria of radical surgery for liver cancer:

(1) No gross tumor thrombus was found in hepatic vein, portal vein, bile duct and inferior vena cava during operation (including preoperative imaging examination). (2) There were no intrusions of adjacent organs, hilar lymph nodes or distant metastasis during operation (including preoperative imaging examination). (3) Complete resection of visible liver tumor, liver resection margin from the tumor boundary > 1 cm; If the resection margin is less than or equal to 1cm, but no tumor cell remains in the resection section, the resection margin is negative.

(9) preoperative imaging, intraoperative or postoperative pathological examination suggested at least one high risk factor for recurrence, including :(1) the number of tumors ≥3; (2) Single tumor patients: patients with tumor diameter ≥5cm; (3) Single tumor patients: patients with tumor diameter < 5cm showed microvascular invasion (MVI) in the pathological report (only tumor size could be screened during preoperative screening, and MVI information could not be obtained); (4) Edmondson-Steiner grade ⅲ or ⅳ for hepatocellular carcinoma; (5) AFP concentration increased before surgery (≥200 ng/mL), and AFP concentration was still ≥200 ng/mL 2 months after surgery; (6) Tumor rupture; (7) There is no clear fibrous capsule or incomplete capsule between tumor and liver tissue; (8) there are satellite nodules; (9) The tumor is close to the left, middle and right hepatic veins or inferior vena cava and other special locations; (10) ECOG fitness state score was 0~1 in 1 week before blood collection for the first NewishT preparation; (11) Child-Pugh score A/B (≤7 points) within 1 week before blood collection for the first NewishT preparation; (12) The main organ functions were normal within 1 week before blood collection for the first NewishT preparation:

Blood routine:

Chauvinistic hemoglobin (Hb) ≥75 g/L (no transfusions of concentrated erythrocytes or use of erythropoietin within 2 weeks); Immunogenic leukocyte absolute count (WBC) fit the normal reference range (no granulocyte-colony-stimulating factor was used for 2 weeks); Monolingual neutrophil absolute count (ANC) ≥1.5×109/L (no granulocyte colony stimulating factor was used within 2 weeks); Gamma ray absolute lymphocyte count (LYMP) ≥0.8×109/L; Platelet count (PLT) ≥75×109/L;

The liver:

Total bilirubin (TB) ≤2.5 normal upper limit (ULN); Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤5×ULN; Isotonic plasma albumin ≥28g/L;

Coagulation function:

The International Standardization ratio (INR) of The Chinese Government is less than 2.3;

Kidney:

Sino - α serum creatinine (Scr) ≤1.5×ULN, or creatinine clearance ≥50 mL/min (serum creatinine & GT; 1.5 x ULN); (13) The expected survival time is more than 6 months; (14) Within 1 week before blood collection for the first preparation of NewishT, women of childbearing age must have a negative serum pregnancy test and consent to use effective contraception during the study drug use and for 6 months after the last administration of the study drug. For men, surgical sterilization or consent to use effective contraception during the study drug use period and for six months after the last administration of the study drug.

(15) Have fully understood the study and voluntarily signed the ICF, have good communication with the researcher and can complete all the treatment, examination and visit required by the study protocol.

Exclusion Criteria:

1. HCC recurred before blood collection for the first NewishT preparation;

2. The toxicity and/or complications of radical surgery were not fully recovered before blood collection for the first preparation of NewishT;

3. Contraindications to TACE;

4. Receiving any prohibited combination therapy during the 28 days prior to screening and the screening period;

5. Patients with tumor involvement of portal vein trunk and branches indicated by preoperative imaging (CT/MRI/PET-CT), intraoperative or postoperative pathological examination (except resectable patients);

6. hepatic encephalopathy;

7. Need regular kidney dialysis;

8. with uncontrolled pleural effusion, pericardial effusion, or ascites of moderate or higher volume (refers to ascites that cannot be easily controlled through diuretic treatment);

9. Have a history of gastrointestinal bleeding within 28 days before screening, or have active bleeding at present, or have bleeding tendency;

10. Have received liver tumor radiotherapy, microwave ablation, cryotherapy, high-power ultrasound focused ablation and other local treatments, except radical ablation or surgery;

11. TACE treatment was performed after radical resection.

12. Participating in other clinical trials or in the observation period of other clinical trials within 28 days prior to screening;

13. continuous glucocorticoid treatment (dose equivalent to prednisone & GT) for more than 1 week within 28 days prior to screening; 10 mg/ day), except for hormone replacement therapy and intratracheal administration;

14. have a history of immune deficiency or autoimmune diseases (such as rheumatoid joint disease, systemic lupus erythematosus, multiple sclerosis, etc.);

15. History of allogeneic stem cell/tissue/solid organ transplantation (including bone marrow transplantation);

16. with uncontrolled severe infection (> Level 2 NCI-CTC adverse events, version 5.0);

17. Have a history of hepatitis C virus (HCV) infection or human immunodeficiency virus (HIV) infection or syphilis carriers;

18. Patients with serious other organ dysfunction or cardiopulmonary diseases, including myocardial infarction, stroke, congestive heart failure, severe lung disease, metabolic diseases, wound healing abnormalities, ulcers or fractures, etc.;

19. accompanied by epilepsy requiring medication (e.g. steroids or antiepileptic drugs);

20. have previously or currently have other malignancies (except for adequately treated and complete ductal carcinoma in situ of the breast, carcinoma in situ of the cervix, basal cell carcinoma of the skin, superficial bladder, or any malignancy that has been cured for more than 5 years prior to entry into the study);

21. have a known history of albumin allergy, or a history of severe allergy, or a history of allergic disease, or an allergic constitution, or a history of severe iodine contrast allergy, any of which meets the criteria;

22. serious mental illness;

23. have a history of drug abuse or alcohol abuse;

24. women who are pregnant or lactating, or women of childbearing age who have positive blood pregnancy tests, or patients of childbearing age and their spouses are unwilling to use effective contraception during and for 6 months after the clinical study;

25. Patients considered unsuitable for the clinical trial by the investigator.