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Hepatocellular Carcinoma (HCC)Early Phase 1SN301ANCT06652243

Clinical Study of SN301A Injection in the Treatment of Hepatocellular Carcinoma

A Early Phase 1 study testing SN301A in people with Hepatocellular Carcinoma (HCC), run by Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine at 1 site in China.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 70 years
Conditions the study is for
Hepatocellular Carcinoma (HCC)
What is being tested?
SN301A
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
12 participants
Where
1 siteChina
Study dates
18 Nov 2024to 31 Oct 2027
Phase
Early Phase 1
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 70 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Signed written informed consent (ICF) and capable of complying with protocol-specified visits and related procedures;
  • Age ≥ 18 years and ≤ 70 years, male or female;
  • 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);
  • 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;
  • Failed at least one prior line of systemic therapy and had used PD-1/L1 and /or TKIs;
  • Child-Pugh A or B 7 points and no history of hepatic encephalopathy;
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  • ECOG score 0-1;
  • Life expectancy of no less than 12 weeks;
  • 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 ;
  • Subjects must provide either fresh tumor tissue samples that meet the requirements or archival tissue within 2 year prior to signing the ICF;
  • 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);
  • 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.

Who cannot join

  • Metastases to central nervous system, including brain metastases and/or meningeal metastases;
  • Prior bone marrow or organ transplant (including but not limited to liver transplant) or waiting for transplant;
  • 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;
  • 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;
  • HLA antibody positive subjects, including weak positive, positive and strong positive (except those with HLA typing different from SN301A cell injection products);
  • Prior treatment with other cellular products or GPC3-targeted agents;
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  • 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;
  • 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;
  • 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;
  • 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;
  • 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;
  • Subjects with fungal, bacterial, viral, tuberculosis or other infection requiring systemic anti-infective treatment within 14 days prior to signing the ICF;
  • Patients with active or previous autoimmune diseases that may recur, such as systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vasculitis, psoriasis, etc.;
  • Previous or current interstitial lung disease, pneumonoultra microscopic pneumonitis, radiation pneumonitis, severely impaired pulmonary function, etc.;
  • 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;
  • 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.
  • 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;
  • 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;
  • Subject is participating in another interventional clinical study;
  • Pregnant or lactating women;
  • Subjects with other conditions that, in the opinion of the investigator, could affect compliance or unsuitability for participation in this study.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

China1 site, 1 recruiting
  • Shanghai General Hospital

    Shanghai, Shanghai Municipality, 200080

    Qi Li, MD, 86-021-60524213, Leeqi2001@hotmail.com

    Jingyi Zhou, MD, 86-021-60524213, jingyi_zhou9468@163.com

    Recruiting

Other trials in China

About this study

Official title: An Early Clinical Study to Evaluate the Safety and Efficacy of SN301A Cell Injection in the Treatment of Subjects with Glypican-3 (GPC3)-Positive Advanced Hepatocellular Carcinoma

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.

Read the 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.

Being tested
SN301A
Keywords
hepatocellular carcinoma, CAR NK, GPC3
Medical subject headings
Carcinoma, Hepatocellular

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • SN301ABiological

    Also called Fludarabine, Cyclophosphamide

    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.

Study groups in NCT06652243
Study groupRoleWhat they receive
SN301A CAR NK cell therapyExperimentalUsing the modified "3 + 3" design principle, a total of 3 dose groups are planned,.There were 1 case in the first group and 3 to 6 cases in each of the last two groups : Dose level 1 (Initial safe dose): 0.5e9 CAR+ NK cells, Dose level 2 (Target effective dose): 1e9 CAR+ NK cells, Dose level 3(Maximum dose): 2e9 CAR+ NK cells Which are administered once on Days 0, 7, and 14 of each 28 day cycle.
Receives: Biological: SN301A

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Dose-limiting toxicities

    Incidence of DLT after the first infusion of SN301A cell injection

    Measured: 28 days post SN301A infusion.

  2. Incidence and severity of adverse events (AEs)and serious adverse events (SAEs) (Safety and Tolerability)

    Any untoward medical event that occurs after a subject has administered an investigational product, which may be manifested as a symptom, sign, disease or laboratory abnormality but does not necessarily have a causal relationship with the investigational product.

    Measured: Through study completion, up to 2 years

Secondary outcomes (13)
  1. Objective response rate (ORR) after SN301A infusion

    Efficacy results of SN301A

    Measured: Through study completion, up to 2 years

  2. Disease control rate (DCR) after SN301A infusion

    Efficacy results of SN301A

    Measured: Through study completion, up to 2 years

  3. Duration of response (DOR) after SN301A infusion

    Efficacy results of SN301A

    Measured: Through study completion, up to 2 years

  4. Progression-free survival (PFS) after SN301A infusion

    Efficacy results of SN301A

    Measured: Through study completion, up to 2 years

  5. Overall survival (OS) after SN301A infusion

    Efficacy results of SN301A

    Measured: Through study completion, up to 2 years

  6. Concentration of alpha fetoprotein (AFP) after SN301A infusion

    Efficacy results of SN301A

    Measured: Through study completion, up to 2 years

  7. Concentration of abnormal prothrombin after SN301A infusion

    Efficacy results of SN301A

    Measured: Through study completion, up to 2 years

  8. Concentration of carbohydrate antigen 19-9 after SN301A infusion

    Efficacy results of SN301A

    Measured: Through study completion, up to 2 years

  9. PK parameters of CAR NK cells in peak peripheral blood (Cmax) after SN301A infusion

    Pharmacokinetic (PK) results of SN301A

    Measured: Through study completion, up to 2 years

  10. PK parameters of CAR NK cells in time to peak peripheral blood (Tmax) after SN301A infusion

    Pharmacokinetic (PK) results of SN301A

    Measured: Through study completion, up to 2 years

  11. PK parameters of CAR NK cells in half-life (t 1/2) after SN301A infusion

    Pharmacokinetic (PK) results of SN301A

    Measured: Through study completion, up to 2 years

  12. PK parameters of CAR NK cells in area under the concentration versus time curve (AUC) after SN301A infusion

    Pharmacokinetic (PK) results of SN301A

    Measured: Through study completion, up to 2 years

  13. Levels of cytokines (IL-6, IFN-γ, TNF-α, IL-15) in peripheral blood after SN301A infusion

    Pharmacokinetic (PK) results of SN301A

    Measured: Through study completion, up to 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted22 Oct 2024
  2. Study start18 Nov 2024
  3. Primary completion31 Oct 2026 (estimated)
  4. Study completion31 Oct 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Early Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
12 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06652243
Sponsor's protocol ID
SN301A-001
Acronym
SN301A
Status last verified
Nov 2024
First submitted
17 Oct 2024
Last updated
25 Nov 2024
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Early Phase 1 study testing SN301A in people with Hepatocellular Carcinoma (HCC), run by Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine at 1 site in China.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 17 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 25 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Qi Li, MD (86-021-60524213, Leeqi2001@hotmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Dose-limiting toxicities (time frame: 28 days post SN301A infusion.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Nov 2024.

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