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

Conditions

Recurrent/Refractory Malignant Lymphoma

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.

Song Y, Ma J, Zhang H, Xie Y, Peng Z, Shuang Y, Li F, Li Y, Yang H, Zou L, Sun X, Zhao W, Huang W, Huang Y, Zhou H, Wang Y, Wang W, Xu J, Deng R, Meng Q, Zhu J.

2025-05-161 citations

10.1038/s41467-025-59461-3

Anti-Btla Antibody Tifcemalimab As a Single Agent or in Combination with Toripalimab in Relapsed/Refractory Lymphomas

Yuqin Song, Jun Ma, Yan Xie, Huilai Zhang, Zhigang Peng et al. (20 authors)

Blood2023-11-02

10.1182/blood-2023-181385

Phase I Study of the Anti-Btla Antibody Tifcemalimab As a Single Agent or in Combination with Toripalimab in Relapsed/Refractory Lymphomas

Jun Ma, Yuqin Song, Yan Xie, Huilai Zhang, Yue-Rong Shuang et al. (18 authors)

Blood2022-11-1512 citations

10.1182/blood-2022-157497

Phase I study of the anti-BTLA antibody icatolimab as a single agent or in combination with toripalimab in relapsed/refractory lymphomas.

Jun Ma, Yan Xie, Huilai Zhang, Yuqin Song, Weili Zhao et al. (11 authors)

Journal of Clinical Oncology2022-06-015 citations

10.1200/jco.2022.40.16_suppl.7578

Interventions

BIOLOGICALJS004 , 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.

BIOLOGICALDrug：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.

Study design

Allocation

NON_RANDOMIZED

Intervention model

SEQUENTIAL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to 70 Years

Healthy volunteers

No

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/

Design outcomes

Primary

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

Secondary

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

Countries

China

Outcome results

None listed