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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 1mg/kg JS004, Q3W until to 2 years | Experimental | Dose escalation, enrolled 3-6 subjects |
|
| 3mg/kg JS004, Q3W until to 2 years | Experimental | Dose escalation, enrolled 3-6 subjects; Dose expansion, enrolled 9 subjects |
|
| 10mg/kg JS004, Q3W until to 2 years | Experimental | Dose escalation, enrolled 3-6 subjects |
|
| 200mg, Q3W until to 2 years | Experimental | Dose expansion, enrolled 9 subjects and indication expansion if RP2D is 200mg |
|
| 240mg JS004+100mg JS001, Q3W until to 2 years | Experimental | Dose escalation, enrolled 3-6 subjects; Dose expansion, enrolled 6-9 subjects and indication expansion if RP2D is confirmed this arm |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| JS004 , Recombinant humanized IgG4k monoclonal antibody specific to BTLA for injection Intravenous infusion | 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. |
| 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 |
| Measure | Description | 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 | |
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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:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Beijing Cancer Hospital | Beijing | Beijing Municipality | China |
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| 240mg JS004+200mg JS001, Q3W until to 2 years | Experimental | Dose escalation, enrolled 3-6 subjects; Dose expansion, enrolled 6-9 subjects and indication expansion if RP2D is confirmed this arm |
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|
| Drug:JS001, Intravenous infusion | 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. |
|
| 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 |
| ID | Term |
|---|---|
| D008223 | Lymphoma |
| ID | Term |
|---|---|
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D008232 | Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
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| ID | Term |
|---|---|
| D007262 | Infusions, Intravenous |
| ID | Term |
|---|---|
| D061605 | Administration, Intravenous |
| D004333 | Drug Administration Routes |
| D004358 | Drug Therapy |
| D013812 | Therapeutics |
| D007263 | Infusions, Parenteral |
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