A Phase 1, Single-arm, Open-label, Dose-escalation Study of JWATM204 as T Cell-targeted Immunotherapy in the Treatment Amongst Subjects With Advanced Hepatocellular Carcinoma

Liver Carcinoma Clinical Trial

Official title:

A Phase 1, Single-arm, Open-label, Dose-escalation Study of JWATM204 as T Cell-targeted Immunotherapy in the Treatment Amongst Subjects With Advanced Hepatocellular Carcinoma

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06144385
• Other study ID #: JWATM204001
• Status: Recruiting
• Phase: Phase 1
• Start date: March 24, 2022
• Est. completion date: December 2024

Study information

• Verified date: December 2023
• Source: Shanghai Ming Ju Biotechnology Co., Ltd.
• Contact: Tao Zhang, MD, PhD
• Phone: +86 027-85726375
• Email: 1277577866[@]qq.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a single arm, open-label, dose escalation clinical study to evaluate the safety and efficacy of infused autologous GPC3-directed CAR-T in patients with advanced hepatocellular carcinoma refractory to prior systematic treatments.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: December 2024
• Est. primary completion date: March 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

1. 18-75 years-old, male or female

2. Voluntarily willing to participate in the study and sign the written informed consent form

3. Life expectation =12 weeks

4. Eastern Cooperative Oncology Group (ECOG) performance status scale =1

5. Histologically-confirmed hepatocellular carcinoma (HCC)

6. No benefits from curative surgery or other local therapies are expected at screening, judged by investigators

7. Radiologically-confirmed progression disease after at least one prior line of systematic treatment and limited benefits from current available options for hepatocellular carcinoma are expected at screening, judged by investigators

8. Fresh samples or formalin-fixed paraffin-embedded (FFPE) samples, immunohistochemistry (IHC)-stained GPC-3 positive

9. Per RECIST v1.1, at least one measurable lesion

10. Barcelona Clinic Liver Cancer (BCLC) stage C or B and Child-Pugh =7

11. No active infections of hepatitis B virus

12. Adequate organ functions

13. Adequate venous access for apheresis

14. Non-hematological AEs induced by previous treatment must have recovered to CTCAE =1, except for alopecia and peripheral neuropathy

15. Women of childbearing potential must agree to use an effective and reliable contraceptive method during 28 days prior to lymphodepletion to 1 year post infusion; Male patients who have not undergone vasectomy and have sexual activity with women of childbearing potential must agree to the use of a barrier contraceptive method since lymphodepletion to 1year post infusion, and sperm donation is prohibited during the study

16. Women of childbearing potential must have negative serum ß-human chorionic gonadotropin (ß-hCG) test result at screening and 48 hours prior to lymphodepletion

Exclusion Criteria:

1. Active brain metastasis

2. Primary lesion or infused lesions with the longest diameter =15 cm, or other potential risk which might not be appropriate for further study treatment judged by the investigator

3. Another primary malignancy within 3 years (with some exceptions for completely-resected early-stage tumors)

4. Systematic autoimmune disorders requiring long-term systematic immunosuppression

5. Previously treated with any genetically engineered modified T-cell therapy nor other cell-gene therapy

6. Active infections of hepatitis C virus (HCV), human immunodeficiency virus (HIV), or syphilis

7. Uncontrolled or active infection at screening, prior to apheresis, 72 hours prior to lymphodepletion or 5 days prior to JWATM204 infusion

8. With severe cardiovascular disease History or presence of clinically-relevant central nervous system (CNS) disorders

9. With clinically-significant CNS disorders

10. Current presence of or previously with hepatic encephalopathy

11. =G2 hemorrhage within 30 days prior to screening, or in need of long-term anticoagulants

12. Pregnant or lactating women

13. Not satisfying pre-defined wash-out period for apheresis

14. Received plasma exchange within 14 days prior to apheresis

15. Unable or unwilling to comply with the study protocol, judged by the investigator, or other situations implying that the subject might not be appropriate to participate in the study

16. Vaccinated with live vaccinations against infectious diseases within 8 weeks prior to JWATM204 infusion

17. Previously allergic or intolerable to JWATM204 or its components

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Hepatocellular
• Hepatic Cell Carcinoma
• Liver Carcinoma

Intervention

Biological:
• CAR-GPC3 T cells
Subjects will undergo leukapheresis to isolate peripheral blood mononuclear cells (PBMCs) for the production of JWATM204 . During JWATM204 production, subjects will receive a preconditioning chemotherapy regimen of cyclophosphamide and fludarabine to deplete the lymphocytes. After lymphodepletion, subjects will receive single-dose treatment with JWATM204 by intravenous (IV) injection.

Locations

Country	Name	City	State
China	Tao Zhang	Wuhan	Hubei

Sponsors (1)

Lead Sponsor	Collaborator
Shanghai Ming Ju Biotechnology Co., Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Rate of dose-limiting toxicities (DLTs)	Dose-limiting toxicity (DLT) is defined as an adverse event that occurred within 28 days after JWATM204 infusion that met any of the following criteria. Any grade =3 nonhematologic toxicity associated with JWATM204 that has not resolved to = grade 2 within 7 days, excluding clinically insignificant abnormalities in laboratory indicators Hematologic toxicity Grade =3 anaphylaxis Grade =3 infection did not resolve to grade =2 within 7 days after anti-infective treatment. = grade 3 autoimmune toxicity during treatment Grade =3 cytokine release syndrome (CRS) during treatment that did not resolve to grade =2 within 72 hours. Grade =3 CAR-T cell-associated encephalopathy syndrome/immune effector cell-associated neurotoxicity syndrome (CRES/ICANS) that did not resolve to grade =2 within 72 hours. Grade 5 events of any nonmalignant cause.	28 days
Primary	Rate and severity of adverse events (AEs) and severe adverse events (SAEs)	An AE is defined as any unfavorable and unintended sign, symptom, or disease (new or worsening) temporally associated with the use of study therapy, regardless of whether or not a causal relationship with the study therapy can be determined.	2 years
Primary	Rate and severity of clinically-significant abnormalities in laboratory testings	Clinically-significant abnormalities in laboratory testings.	2 years
Secondary	Copy number of the vector transgene of JWATM204 in peripheral blood	The pharmacokinetic parameters of JWATM204 will be evaluated by quantitative polymerase chain reaction (qPCR) for the copy number of the vector transgene of JWATM204 in peripheral blood to evaluate T-cell expansion and persistence.	1 year
Secondary	Objective response rate (ORR)	Proportion of patients whose tumor volume has reached a predetermined value and can maintain a minimum time limit, including complete response and partial response patients.	2 years
Secondary	Disease Control Rate (DCR)	The percentage of patients with advanced or metastatic cancer who have achieved complete response, partial response and stable disease to a therapeutic intervention in clinical trials of anticancer agents.	2 years
Secondary	Progression-free survival (PFS)	Defined as time from randomisation to first progression by investigator assessment using revised Response Evaluation Criteria in Solid Tumours (RECIST) guidelines (version 1.1) or death (by any cause in the absence of progression)	2 years
Secondary	Overal survival (OS)	Defined as the time from randomisation to death due to any cause.	2 years