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

A Phase I Clinical Study of Recombinant Humanized Anti-BTLA Monoclonal Antibody (JS004) in Patients With Recurrent/Refractory Malignant Lymphoma

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.

Study Overview

• Status: Completed
• Conditions: Recurrent/Refractory Malignant Lymphoma
• Intervention / Treatment: Biological: JS004 , Recombinant humanized IgG4k monoclonal antibody specific to BTLA for injection Intravenous infusion; Biological: Drug：JS001, Intravenous infusion

• Study Type: Interventional
• Enrollment (Actual): 71
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China
      • Beijing Cancer Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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
11. Unresolved toxicities from prior anticancer therapy, defined as having not resolved to baseline or to NCI-CTCAE v5.0 Grade 0 or 1, or to levels dictated in the inclusion/exclusion criteria with the exception of alopecia.Subjects with irreversible toxicity that is not reasonably expected to be exacerbated by TAB004 may be included (e.g., hearing loss) after consultation with the medical monitor.
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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1mg/kg JS004, Q3W until to 2 years; Dose escalation, enrolled 3-6 subjects	Biological: 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.; Other Names: TAB004
Experimental: 3mg/kg JS004, Q3W until to 2 years; Dose escalation, enrolled 3-6 subjects; Dose expansion, enrolled 9 subjects	Biological: 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.; Other Names: TAB004
Experimental: 10mg/kg JS004, Q3W until to 2 years; Dose escalation, enrolled 3-6 subjects	Biological: 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.; Other Names: TAB004
Experimental: 200mg, Q3W until to 2 years; Dose expansion, enrolled 9 subjects and indication expansion if RP2D is 200mg	Biological: 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.; Other Names: TAB004
Experimental: 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	Biological: 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.; Other Names: TAB004; 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.
Experimental: 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	Biological: 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.; Other Names: TAB004; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants and severiaty with treatment-related Adverse events as assessed by CTCAE V5.0	Safety and Tolerability	2 Years

Secondary Outcome Measures

Outcome Measure	Time Frame
Objective Response Rate (ORR) per Lugano response critieria 2014 for Lymphoma	2 Years
Duration of Response (DOR) per Lugano response critieria 2014 for Lymphoma	2 Years
Disease Control Rate (DCR) per Lugano response critieria 2014 for Lymphoma	2 Years
Progrssion-free survival (PFS) per Lugano response critieria 2014 for Lymphoma	2 Years

Collaborators and Investigators

• Sponsor: Shanghai Junshi Bioscience Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): July 17, 2020
• Primary Completion (Actual): March 14, 2024
• Study Completion (Actual): March 14, 2024

Study Registration Dates

• First Submitted: July 16, 2020
• First Submitted That Met QC Criteria: July 17, 2020
• First Posted (Actual): July 20, 2020

Study Record Updates

• Last Update Posted (Actual): May 16, 2024
• Last Update Submitted That Met QC Criteria: May 15, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Disease Attributes; Lymphoma; Recurrence; Physiological Effects of Drugs; Immunologic Factors; Antibodies; Antibodies, Monoclonal
• Other Study ID Numbers: JS004-002-I

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No