Trial Title:
A Phase 1 Study of BST02 in Treating Locally Advanced Liver Cancer
NCT ID:
NCT06526832
Condition:
Locally Advanced Liver Carcinoma
Conditions: Official terms:
Liver Neoplasms
Carcinoma, Hepatocellular
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Biological
Intervention name:
BST02
Description:
BST02 is a tumor infiltrating lymphocyte product manufactured from the sample collected
in the patient's tumor lesion.
Arm group label:
BST02
Summary:
The goal of this clinical trial is to investigate the BST02, a tumor infiltrating
lymphocyte product, collected from the locally advanced liver cancer subjects
The main questions it aims to answer are:
1. Safety and tolerability of BST02.
2. Preliminary efficacy of BST02. Participants will receive a cytoreductive surgery to
collect samples for the manufacture of BST02.
Participants will receive BST02 infusion followed by IL-2 infusion. Blood samples will be
collected for the analysis of PK and safety.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Age of 18-75 years (inclusive);
2. Patients with histologically or cytologically confirmed advanced liver cancer
(including hepatocellular carcinoma and intrahepatic cholangiocarcinoma) staged
according to the Barcelona Clinic Liver Cancer (BCLC) Classification Criteria as
stage C or stage B unsuitable for local treatment/progression on local treatment; or
intrahepatic cholangiocarcinoma that is unresectable, recurrent, or metastatic (AJCC
2017, 8th edition, TNM staging of stage IV).
3. Failure (disease progression or intolerability) after at least first-line
guideline-recommended systemic therapy (Atezolizumab + Bevacizumab, Sintilimab +
Bevacizumab analogs; Donafenib, Lenvatinib, Sorafenib; FOLFOX4; Gemcitabine in
combination with Cis-platin, etc.), refused to receive the standard systemic therapy
by the subject, or deemed inappropriate for standard systemic therapy by the
investigator;
4. At least one surgically resectable tumor lesion that has not received radiation
therapy or other local treatment within 28 days which will be used to prepare BST02
cells;
5. At least one measurable lesion in line with the definition of mRECIST criteria after
TIL sampling surgery. If the target lesion is intrahepatic, arterial phase
enhancement imaging is required;
6. Eastern Cooperative Oncology Group (ECOG) score≤1;
7. Child-Pugh score for hepatic cirrhosis ≤7;
8. Expected survival time≥3 months;
9. Adequate organ and bone marrow functions, as defined below, at the time of
assessment during the screening and preparation period (within 14 days prior to TIL
sampling):
Hematology: Absolute Neutrophil Count (ANC)≥1.5×109/L, Blood Platelet Count
(PLT)≥90×109/L, Hemoglobin (HGB)≥80 g/L (no transfusion or erythropoietin treatment
within 14 days); Hepatic function: Alanine Aminotransferase (ALT) and Aspartate
Aminotransferase (AST) levels≤5 × Upper Limit of Normal (ULN); Serum Total Bilirubin
(TBil) ≤ 1.5×ULN; if Gilbert's syndrome is diagnosed: TBil ≤ 3×ULN; Coagulation
function: Activated partial thromboplastin time (APTT) ≤ 1.5×ULN, while
International Normalized Ratio (INR), Prothrombin Time (PT) ≤ 1.5×ULN; Renal
function: Serum creatinine (Cr)≤1.5×ULN or Creatinine Clearance (Ccr) ≥ 60mL/min
(Cockcroft-Gault formula); Cardiac function test: Left Ventricular Ejection
Fractions (LVEF)≥50% by echocardiography; arrhythmia with no need for treatment,
Fridericia QT correction formulas (QTcF)≤470 ms (QTcF is calculated using the
Fridericia formula, i.e., QTcF = QT/(RR^0.33), RR is the standardized heart rate
value, RR=60/heart rate; if the results of the first test are abnormal, the test can
be repeated twice at an interval of at least 5 minutes and the comprehensive
result/mean value should be considered to determine the eligibility); Lung function:
Percentage of FEV1 to the predicted value (FEV1%) ≥ 60%;
10. Prior treatment-induced adverse reactions have recovered to ≤ grade 1 according to
the Common Terminology Criteria for Adverse Events (CTCAE) 5.0 (except for
toxicities such as alopecia, grade 2 or less peripheral neurotoxicity, and other
toxicities that do not pose a safety risk as determined by the investigator) prior
to TIL sampling;
11. Subjects agree to use effective contraceptives from the time of signing the informed
consent form until 6 months after infusion of BST02 cells (non-drug measures for
contraception must be taken);
12. Subjects should fully understand the trial and voluntarily sign the informed consent
form, and be able to comply with the visits and related procedures specified in the
protocol.
Exclusion Criteria:
1. Pregnant or lactating women;
2. Subjects with a prior history of severe allergy and hypersensitivity to the
investigational drugs including, but not limited to, cyclophosphamide, fludarabine,
IL-2, and the components of BST02;
3. Subjects with prior or current history of hepatic encephalopathy; patients with
known central nervous system metastases uncontrolled by other treatment or
untreated; with exception of patients who have stabilized their symptoms after
treatment, and discontinued the treatment of glucocorticoid and anticonvulsant
medications ≥4 weeks prior to lymphodepletion preconditioning;
4. Presence of clinically significant ascites, defined as: Positive signs of ascites on
physical examination or ascites that needs to be controlled with interventional
therapy (only those with ascites on imaging without intervention may be included);
(5) The Indocyanine Green retention test after 15 min (ICG-R15) is ≥30%;
(6) History of organ transplantation, hematopoietic stem cell transplantation; (7) Other
serious medical conditions that may limit the subject's participation in this trial,
including but not limited to: Hypertension that is uncontrolled by medication (systolic
blood pressure ≥160 mmHg or diastolic blood pressure ≥100 mmHg at rest after taking
medication); Uncontrolled diabetes: Fasting blood glucose levels remain above 1 mmol/L
after standardized treatment with insulin; Unstable cardiovascular diseases: Uncontrolled
congestive cardiac failure, infarct myocardial or unstable arrhythmia or unstable
arrhythmia within the last 6 months, percutaneous coronary interventional procedure,
acute coronary syndromes, coronary artery bypass transplant; cerebrovascular accident,
transient ischemic attack, cerebral embolism, deep vein thrombosis, etc.; Uncontrolled
respiratory system disorder: Pulmonary embolism, chronic obstructive pulmonary disease,
interstitial lung disease, etc.; Active, autoimmune diseases requiring systemic therapy
during the period of the study: Subjects with eczema, vitiligo, psoriasis, alopecia, or
Graves's disease who do not require systemic treatment within the last 2 years, other
autoimmune disorders that are not expected to recur, and subjects with type I diabetes
mellitus who require only insulin replacement therapy may be enrolled; Active infection
or active tuberculosis infection with a need for systemic therapy; Mental illness, except
for mild depression, and other mild conditions; (8) Patients who are HIV-positive, or
positive for syphilis spirochete antibodies; Patients with active hepatitis B or C are
required to adopt antiviral therapy during the whole study. Active hepatitis B is defined
as positive hepatitis B core antibody (HBcAb) or hepatitis B surface antigen (HBsAg) and
HBV-DNA >2000 IU/ml. Active hepatitis C is defined as HCV RNA above the lower limit of
detection; (9) Subjects have taken any immunosuppressive drugs, such as corticosteroids,
within 4 weeks prior to TIL sampling or had combined diseases needing application of
immunosuppressive medications for the duration of the trial as judged by the
investigator. However, physiologic doses of glucocorticoids (i.e., a maximum dose of 15
mg/day for prednisone or an equivalent dose of other glucocorticoids) are permitted, and
inhalational, intranasal, topical, or prophylaxis use of corticosteroids are allowed
against contrast allergy; (10) Subjects who have received anti-PD-1/ PD-L1 monoclonal
antibody treatment within 4 weeks prior to lymphodepletion preconditioning , or undergone
local treatments such as surgery (except BST02 sampling surgery), interventional therapy,
radiotherapy, ablation, or systemic therapy against liver cancer (including those who
participated in other clinical trials of drug therapy; metabolism of drugs with 5
half-lives of less than 4 weeks, whichever is shorter); or immunotherapy such as
thymopeptide, interferon, or any traditional Chinese medicine used for tumor control
within 1 week prior to lymphodepletion preconditioning ; (11) Subjects who have received
a live vaccine within 3 months prior to screening or planned to receive a live vaccine
during the trial; (12) Subjects who have undergone major surgery within 4 weeks prior to
screening or planned to receive surgery during the trial period (except for TIL sampling
surgery); (13) Patients with surgical complications or delayed wound healing prior to
lymphodepletion preconditioning who, in the judgment of the investigator, will be at
increased risk for lymphodepletion, TIL therapy, IL-2 adjuvant therapy, or infection;
(14) Subjects who have diagnosed as combined other primary malignant neoplasm within 5
years prior to screening, excluding radically treated basal cell carcinoma of skin,
squamous cell carcinoma of skin, and/or radically resected carcinoma in situ; (15)
Subjects who have received cell therapy products 6 months prior to lymphodepletion
preconditioning; (16) Subjects with known alcoholism, drug or substance abuse, and others
who, in the opinion of the investigator, are not suitable for participation in this
trial.
Gender:
All
Minimum age:
18 Years
Maximum age:
75 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Sun Yat-sen University Cancer Center
Address:
City:
Guangzhou
Zip:
510000
Country:
China
Status:
Recruiting
Contact:
Last name:
Yaojun Zhang, PhD
Phone:
020-87342219
Email:
zhangyuj@sysucc.org.cn
Investigator:
Last name:
Yaojun Zhang, PhD
Email:
Principal Investigator
Start date:
July 4, 2024
Completion date:
December 3, 2025
Lead sponsor:
Agency:
BioSyngen Pte Ltd
Agency class:
Industry
Source:
BioSyngen Pte Ltd
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06526832
