Trial Title:
Clinical Study of SN301A Injection in the Treatment of Hepatocellular Carcinoma
NCT ID:
NCT06652243
Condition:
Hepatocellular Carcinoma (HCC)
Conditions: Official terms:
Carcinoma
Carcinoma, Hepatocellular
Cyclophosphamide
Fludarabine
Conditions: Keywords:
hepatocellular carcinoma
CAR NK
GPC3
Study type:
Interventional
Study phase:
Early Phase 1
Overall status:
Not yet recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Biological
Intervention name:
SN301A
Description:
SN301A is an investigational off-the-shelf CAR NK cell therapy, armed with calibrated
release (cr)IL15, designed to selectively target and treat GPC3 expressing advanced
hepatocellular carcinoma.
Subjects will receive lymphodepletion pretreatment (Fludarabine/Cyclophosphamide), three
SN301A intravenous infusions in a cycle (D0, D7, D14), with each subject receiving a
maximum of 3 cycles.
Arm group label:
SN301A CAR NK cell therapy
Other name:
Fludarabine
Other name:
Cyclophosphamide
Summary:
This is a single-arm, open-label study of safety, tolerability, and anti-cancer activity
of SN301A (an off-the-shelf CAR NK cell therapy) in patients with glypican-3
(GPC3)-positive advanced hepatocellular carcinoma.
Detailed description:
This study is a single-arm, open-label, modified 3+3 dose-escalation early exploratory
clinical study to evaluate the safety, tolerability, Pharmacokinetic (PK), and
Pharmacodynamic (PD) of SN301A cell injection in the treatment of subjects with
glypican-3 (GPC3)-positive advanced hepatocellular carcinoma, and evaluate the efficacy
of SN301A cell injection in the treatment of subjects with GPC3-positive advanced
hepatocellular carcinoma.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Signed written informed consent (ICF) and capable of complying with
protocol-specified visits and related procedures;
2. Age ≥ 18 years and ≤ 70 years, male or female;
3. According to the Guidelines for the Diagnosis and Treatment of Primary Liver Cancer
of CSCO in 2024, hepatocellular carcinoma was Diagnosed and GPC3 expression was
positive by immunohistochemistry (GPC3 positive was defined as staining positive
i.e. ≥ 2 + as defined by Kaseb et al);
4. Barcelona Clinic Liver Cancer (BCLC) stage determined to be unresectable Stage B or
C hepatocellular carcinoma, including: disease progression following surgical/local
therapy or unsuitable for surgical/local therapy, recurrent or metastatic HCC;
5. Failed at least one prior line of systemic therapy and had used PD-1/L1 and /or
TKIs;
6. Child-Pugh A or B 7 points and no history of hepatic encephalopathy;
7. ECOG score 0-1;
8. Life expectancy of no less than 12 weeks;
9. Subjects with at least 1 measurable lesion according to RECIST v1.1 and mRECIST (a
lesion that has undergone local therapy such as radiation therapy or interventional
therapy cannot be considered measurable unless imaging evidence confirms unequivocal
progression of the lesion), RECIST v1.1 i.e., non-nodal lesions ≥ 10 mm in longest
diameter and/or nodal lesions ≥ 15 mm in short diameter on CT or MRI; mRECIST refers
to non-lymph node measurable disease criteria meeting RECIST v1.1 criteria (hilar
lymph nodes must have short axis ≥ 20 mm) and demonstrating intratumoral arterial
enhancement on contrast-enhanced CT or MRI ;
10. Subjects must provide either fresh tumor tissue samples that meet the requirements
or archival tissue within 2 year prior to signing the ICF;
11. Subject has adequate organ and bone marrow function and meets the following
laboratory criteria:
- Bone marrow function: absolute neutrophil count (ANC) ≥ 1.5e9/L; platelets
(PLT) ≥ 75e9/L (transfusion or use of hematopoietic stimulating factors was not
acceptable within 14 days prior to Screening);
- Hemoglobin ≥ 90g/L;
- Liver function: total bilirubin ≤ 2.5 × ULN; alanine aminotransferase ≤ 5 ×
ULN; aspartate aminotransferase ≤ 5 × ULN;
- Renal function: serum creatinine ≤ 1.5 × ULN, or creatinine clearance ≥ 60
mL/min (calculated using the Cockcroft-Gault formula);
- Coagulation: International normalized ratio (INR) ≤ 1.5 × ULN, activated
partial thromboplastin time (APTT) ≤ 1.5 × ULN (INR between 2.0 and 3.0 is
required for subjects receiving prophylactic anticoagulant therapy);
12. Men and women of childbearing potential must agree to use effective contraception
from signing the ICF until one year after the last cell infusion and must have a
negative serum pregnancy test at screening for women of childbearing potential.
Exclusion Criteria:
1. Metastases to central nervous system, including brain metastases and/or meningeal
metastases;
2. Prior bone marrow or organ transplant (including but not limited to liver
transplant) or waiting for transplant;
3. Previous or concurrent history of other malignancies, except for carcinoma in situ
of the uterine cervix that has been cured and has not recurred for at least 2 years
before screening, noninvasive basal cell or squamous cell skin cancer, or ductal
carcinoma in situ after radical treatment for localized prostate cancer and radical
resection;
4. Hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) positive
and HBV DNA > 500 IU/mL (lower limit of detection; HBV DNA ≤ 500 IU/mL,
lymphodepletion pretreatment requires antiviral therapy for at least 14 days before
treatment and can be enrolled if antiviral therapy is continued during the study);
hepatitis C virus (HCV) antibody positive and HCV RNA positive; human
immunodeficiency virus (HIV) antibody positive; syphilis antibody positive;
5. HLA antibody positive subjects, including weak positive, positive and strong
positive (except those with HLA typing different from SN301A cell injection
products);
6. Prior treatment with other cellular products or GPC3-targeted agents;
7. Received any fluoropyrimidine chemotherapeutic agents or small-molecule targeted
agents within 14 days or 5 half-lives (whichever is shorter) prior to signing the
ICF; received any antineoplastic biological agents or non-fluoropyrimidine
chemotherapeutic agents within 28 days prior to signing the ICF; received wide-range
radiotherapy within 28 days prior to signing the ICF, received local radiotherapy
for non-target lesions to relieve symptoms within 14 days prior to signing the ICF;
received traditional Chinese medicine/Chinese herbal medicine and local
interventional therapy with anti-tumor indications within 14 days prior to signing
the ICF;
8. Adverse events resulting from prior anticancer therapy have not recovered to Grade 1
or baseline, except for alopecia, Grade 2 peripheral neurotoxicity, hypothyroidism
stabilized by hormone replacement;
9. Subjects who have received attenuated live vaccine immunization within 28 days prior
to signing ICF or need to receive attenuated live vaccine immunization during the
study;
10. Major surgical treatment (except liver mass biopsy) within 28 days prior to signing
the ICF, or the need for major surgical treatment during the study;
11. Requiring chronic systemic corticosteroids (at doses ≥ 10 mg/day prednisone or
equivalent) or other immunosuppressive medications within 14 days prior to the first
study drug infusion or during the study, except for inhaled or topical use;
12. Subjects with fungal, bacterial, viral, tuberculosis or other infection requiring
systemic anti-infective treatment within 14 days prior to signing the ICF;
13. Patients with active or previous autoimmune diseases that may recur, such as
systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease,
vasculitis, psoriasis, etc.;
14. Previous or current interstitial lung disease, pneumonoultra microscopic
pneumonitis, radiation pneumonitis, severely impaired pulmonary function, etc.;
15. Third space effusion that is not clinically well controlled before screening, such
as pleural effusion and ascites that cannot be controlled by drainage or other
methods;
16. History of serious cardiovascular and cerebrovascular diseases, including but not
limited to in:
- Patients with severe heart rhythm or conduction abnormalities, such as
ventricular arrhythmia requiring clinical intervention, grade II-III
atrioventricular block;
- QT interval corrected by Fridericias formula (QTcF) prolongation > 450 ms for
males; > 470 ms for females;
- Acute coronary syndrome, congestive heart failure, aortic dissection, stroke,
or other ≥ Grade 3 cardiovascular or cerebrovascular event within 6 months
prior to Screening;
- Presence of heart failure of New York Heart Association (NYHA) Functional Class
≥ II or left ventricular ejection fraction (LVEF) > 50%;
- Clinically uncontrolled hypertension, systolic blood pressure ≥ 160 mmHg and/or
diastolic blood pressure ≥ 100 mmHg.
17. Patients with history of pulmonary embolism or severe lower extremity deep venous
thrombosis requiring interventional treatment such as inferior vena cava filter
implantation or therapeutic dose of anticoagulants at screening;
18. Investigator assessment of intrahepatic tumor mass greater than 50% of the entire
liver, or tumor thrombus invading major vessels such as the main portal vein,
superior mesenteric vein, or inferior vena cava causing complications such as portal
hypertension or associated clinical risks;
19. Subject is participating in another interventional clinical study;
20. Pregnant or lactating women;
21. Subjects with other conditions that, in the opinion of the investigator, could
affect compliance or unsuitability for participation in this study.
Gender:
All
Minimum age:
18 Years
Maximum age:
70 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Shanghai General Hospital
Address:
City:
Shanghai
Zip:
200080
Country:
China
Contact:
Last name:
Qi Li, MD
Phone:
86-021-60524213
Email:
Leeqi2001@hotmail.com
Contact backup:
Last name:
Jingyi Zhou, MD
Phone:
86-021-60524213
Email:
jingyi_zhou9468@163.com
Contact backup:
Last name:
Qi Li, MD
Start date:
November 30, 2024
Completion date:
October 31, 2027
Lead sponsor:
Agency:
Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine
Agency class:
Other
Collaborator:
Agency:
Celest Therapeutics Co. Ltd
Agency class:
Other
Collaborator:
Agency:
Senti Biosciences
Agency class:
Industry
Source:
Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06652243
