Clinical Study of SN301A Injection in the Treatment of Hepatocellular Carcinoma

NCT06652243 | Recruiting Early Phase 1

• 1 other identifier: SN301A-001
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Hepatocellular Carcinoma (HCC)

Keywords

hepatocellular carcinoma; CAR NK; GPC3

Outcome Measures

Primary Outcomes (2)

• Dose-limiting toxicities

  Incidence of DLT after the first infusion of SN301A cell injection

  28 days post SN301A infusion.

• 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.

  Through study completion, up to 2 years

Secondary Outcomes (13)

• Objective response rate (ORR) after SN301A infusion

  Through study completion, up to 2 years

• Disease control rate (DCR) after SN301A infusion

  Through study completion, up to 2 years

• Duration of response (DOR) after SN301A infusion

  Through study completion, up to 2 years

• Progression-free survival (PFS) after SN301A infusion

  Through study completion, up to 2 years

• Overall survival (OS) after SN301A infusion

  Through study completion, up to 2 years

Study Arms (1)

SN301A CAR NK cell therapy

EXPERIMENTAL

Using 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.

Biological: SN301A

Interventions

SN301A BIOLOGICAL

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.

Also known as: Fludarabine, Cyclophosphamide

SN301A CAR NK cell therapy

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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;
• 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);

You may not qualify if:

• 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;
• 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;

Sponsors & Collaborators

• Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine: lead
• Celest Therapeutics Co. Ltd: collaborator
• Senti Biosciences: collaborator

Study Sites (1)

Shanghai General Hospital

Shanghai, Shanghai Municipality, 200080, China

RECRUITING

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

fludarabine; Cyclophosphamide

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Central Study Contacts

Qi Li, MD

CONTACT

86-021-60524213; Leeqi2001@hotmail.com

Jingyi Zhou, MD

CONTACT

86-021-60524213; jingyi_zhou9468@163.com

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head of Oncology

Study Record Dates

• First Submitted: October 17, 2024
• First Posted: October 22, 2024
• Study Start: November 18, 2024
• Primary Completion (Estimated): October 31, 2026
• Study Completion (Estimated): October 31, 2027
• Last Updated: November 25, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)