A Phase I Clinical Study of JS004 in Subjects With Recurrent/Refractory Malignant Lymphoma of China

NCT ID: NCT04477772

Last Updated: 2024-05-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 71 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-07-17
• Study Completion Date: 2024-03-14

Brief Summary

A First-in-human, dose-escalation, dose-expansion phase I clinical study of JS004 in subjects with recurrent/refractory malignant lymphoma in China, to evaluate the safety, tolerbility, PK, immunogenicity,antitumor activity and biomarkers of JS004, to define MTD and RP2D of JS004. A cycle is 21 days(3 weeks) which includes JS004 being administered IV Q3W and JS004 combine with JS001 being administered IV Q3W. All patients will be treated until disease progression per Lugano response critieria 2014 for Lymphoma or intolerable toxicity per CTCAE 5.0, withdrawal of consent, or end of the study, whichever occurs first. Disease progression must be confirmed at least 4 weeks but no longer than 8 weeks after initial documentation of progression.

Conditions

Recurrent/Refractory Malignant Lymphoma

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

1mg/kg JS004, Q3W until to 2 years

Dose escalation, enrolled 3-6 subjects

Group Type: EXPERIMENTAL

JS004 , Recombinant humanized IgG4k monoclonal antibody specific to BTLA for injection Intravenous infusion

Intervention Type: BIOLOGICAL

Part A: including dose escalation (1mg/kg JS004; 3mg/lg JS004; 10mg/kg JS004), dose expansion (3mg/kg JS004 and 200mg JS004) and indication expansion. Part B: including dose escalation (240mg JS004+100mg JS001; 240mg JS004+ 200mg JS001), dose expansion (240mg JS004+100mg JS001; 240mg JS004+ 200mg JS001) and indication expansion.

3mg/kg JS004, Q3W until to 2 years

Dose escalation, enrolled 3-6 subjects; Dose expansion, enrolled 9 subjects

Group Type: EXPERIMENTAL

JS004 , Recombinant humanized IgG4k monoclonal antibody specific to BTLA for injection Intravenous infusion

Intervention Type: BIOLOGICAL

Part A: including dose escalation (1mg/kg JS004; 3mg/lg JS004; 10mg/kg JS004), dose expansion (3mg/kg JS004 and 200mg JS004) and indication expansion. Part B: including dose escalation (240mg JS004+100mg JS001; 240mg JS004+ 200mg JS001), dose expansion (240mg JS004+100mg JS001; 240mg JS004+ 200mg JS001) and indication expansion.

10mg/kg JS004, Q3W until to 2 years

Dose escalation, enrolled 3-6 subjects

Group Type: EXPERIMENTAL

JS004 , Recombinant humanized IgG4k monoclonal antibody specific to BTLA for injection Intravenous infusion

Intervention Type: BIOLOGICAL

Part A: including dose escalation (1mg/kg JS004; 3mg/lg JS004; 10mg/kg JS004), dose expansion (3mg/kg JS004 and 200mg JS004) and indication expansion. Part B: including dose escalation (240mg JS004+100mg JS001; 240mg JS004+ 200mg JS001), dose expansion (240mg JS004+100mg JS001; 240mg JS004+ 200mg JS001) and indication expansion.

200mg, Q3W until to 2 years

Dose expansion, enrolled 9 subjects and indication expansion if RP2D is 200mg

Group Type: EXPERIMENTAL

JS004 , Recombinant humanized IgG4k monoclonal antibody specific to BTLA for injection Intravenous infusion

Intervention Type: BIOLOGICAL

Part A: including dose escalation (1mg/kg JS004; 3mg/lg JS004; 10mg/kg JS004), dose expansion (3mg/kg JS004 and 200mg JS004) and indication expansion. Part B: including dose escalation (240mg JS004+100mg JS001; 240mg JS004+ 200mg JS001), dose expansion (240mg JS004+100mg JS001; 240mg JS004+ 200mg JS001) and indication expansion.

240mg JS004+100mg JS001, Q3W until to 2 years

Dose escalation, enrolled 3-6 subjects; Dose expansion, enrolled 6-9 subjects and indication expansion if RP2D is confirmed this arm

Group Type: EXPERIMENTAL

JS004 , Recombinant humanized IgG4k monoclonal antibody specific to BTLA for injection Intravenous infusion

Intervention Type: BIOLOGICAL

Part A: including dose escalation (1mg/kg JS004; 3mg/lg JS004; 10mg/kg JS004), dose expansion (3mg/kg JS004 and 200mg JS004) and indication expansion. Part B: including dose escalation (240mg JS004+100mg JS001; 240mg JS004+ 200mg JS001), dose expansion (240mg JS004+100mg JS001; 240mg JS004+ 200mg JS001) and indication expansion.

Drug：JS001, Intravenous infusion

Intervention Type: BIOLOGICAL

Part B: including dose escalation (240mg JS004+100mg JS001; 240mg JS004+ 200mg JS001), dose expansion (240mg JS004+100mg JS001; 240mg JS004+ 200mg JS001) and indication expansion.

240mg JS004+200mg JS001, Q3W until to 2 years

Dose escalation, enrolled 3-6 subjects; Dose expansion, enrolled 6-9 subjects and indication expansion if RP2D is confirmed this arm

Group Type: EXPERIMENTAL

JS004 , Recombinant humanized IgG4k monoclonal antibody specific to BTLA for injection Intravenous infusion

Intervention Type: BIOLOGICAL

Part A: including dose escalation (1mg/kg JS004; 3mg/lg JS004; 10mg/kg JS004), dose expansion (3mg/kg JS004 and 200mg JS004) and indication expansion. Part B: including dose escalation (240mg JS004+100mg JS001; 240mg JS004+ 200mg JS001), dose expansion (240mg JS004+100mg JS001; 240mg JS004+ 200mg JS001) and indication expansion.

Drug：JS001, Intravenous infusion

Intervention Type: BIOLOGICAL

Part B: including dose escalation (240mg JS004+100mg JS001; 240mg JS004+ 200mg JS001), dose expansion (240mg JS004+100mg JS001; 240mg JS004+ 200mg JS001) and indication expansion.

Interventions

JS004 , Recombinant humanized IgG4k monoclonal antibody specific to BTLA for injection Intravenous infusion

Part A: including dose escalation (1mg/kg JS004; 3mg/lg JS004; 10mg/kg JS004), dose expansion (3mg/kg JS004 and 200mg JS004) and indication expansion. Part B: including dose escalation (240mg JS004+100mg JS001; 240mg JS004+ 200mg JS001), dose expansion (240mg JS004+100mg JS001; 240mg JS004+ 200mg JS001) and indication expansion.

Intervention Type: BIOLOGICAL

Drug：JS001, Intravenous infusion

Part B: including dose escalation (240mg JS004+100mg JS001; 240mg JS004+ 200mg JS001), dose expansion (240mg JS004+100mg JS001; 240mg JS004+ 200mg JS001) and indication expansion.

Intervention Type: BIOLOGICAL

Other Intervention Names

TAB004

Eligibility Criteria

Inclusion Criteria

1.Able to understand and sign informed consent voluntarily

2.18-70 years old

3.Pathologically confirmed malignant lymphoma

4.ECOG PS: 0-1

5.Expected survival ≥12 weeks

6.At least one measurable lesion per Lugano response critieria 2014 for Lymphoma

7.Adequate organ and marrow function, as defined below:

ANC≥1.5×109/L;

PLT≥100×109/L and ≥75×109/L for subjects with bone marrow involvement;

Hb≥90 g/L;

TBIL≤1.5 ULN, ≤2 ULN in those with hep109atic metastasis, except subjects with documented Gilbert's syndrome who must have a baseline conjugated bilirubin ≤3.0 mg/dL;

AST and ALT≤2.5 ULN, ≤5 ULN in those with hepatic metastasis;

Cr≤1.5 UL, or creatinine clearance≥50mL/min for subject;

INR ≤2 ULN and aPTT≤1.5×ULN for those with no prior anticoagulant therapy.

8.According to Fridericia's principle, QTC results need to match : Male≤450 ms，Female≤470 ms

9.Females of childbearing potential need to use effective contraception

Exclusion Criteria

1. Patients with known allergy to macromolecular protein preparations or JS004 components

2. Prior exposure to anti-BTLA or anti-HVEM antibodies

3. Enrolled in other clinical studies within 4 weeks prior to the first dose of study treatment

4. Major surgery within 4 weeks prior to the first dose of study treatmentor still recovering from prior surgery

5. Patients who discontinued previous immunotherapy due to immune-related adverse reactions

6. Immunosuppressive agents have been used within 4 weeks prior to the first dose of study treatment

7. Prior allogeneic bone marrow transplantation or solid organ transplantation

8. Live attenuated vaccine be administered 30 days before the first dose of study treatment

9. Two or more malignancies developed within 5 years prior to first dose of study treatment

10. The patients have symptomatic, untreated, or requiring ongoing treatment central nervous system (CNS) metastases

12. Autoimmune disease within the previous 2 years

13. A history of rapid allergic reaction, eczema, or asthma beyond the control of topical corticosteroids

14. A history of primary immunodeficiency

15. Concomitant disease that is not under control, including but not limited to: persistent or active infection, unexplained fever > 38.5°C, or heart disease, active peptic ulcer disease or gastritis

16. A history of active inflammatory bowel disease

17. HIV(+)

18. Patients with evidence of hepatitis B virus (HBV) or hepatitis C virus (HCV) infection

19. Pregnant or lactating woman

20. Patients with vitiligo, alopecia, and hormonal replacement therapy have controlled endocrine defects

21. Any other medical factors that may affect subjects' rights, safety, compliance, ability to sign informed consent, and interpretation of study results.

22. Have a history of psychotropic drug abuse and unable to withdraw or have mental disorders.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Shanghai Junshi Bioscience Co., Ltd.

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Beijing Cancer Hospital

Beijing, Beijing Municipality, China

Countries

China

Other Identifiers

JS004-002-I

Identifier Type: -

Identifier Source: org_study_id