A Study of GNC-038, a Tetra-specific Antibody, in Participants With R/R Non-Hodgkin Lymphoma
Study Details
Study Description
Brief Summary
In this study, the safety and tolerability of GNC-038 in participants with recurrent or refractory Non-Hodgkin lymphoma will be investigated to assess the dose-limiting toxicity (DLT), maximum tolerated dose (MTD) or maximum administered dose (MAD) for MTD is not reached of GNC-038. The recommended dose for future clinical study will also be determined.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Study treatment Patients receive GNC-038 as intravenous infusion for one cycle. Participants with no intolerable AEs could continue for another three cycles. Participants with a clinical benefit after four cycles' treatment could also receive additional treatment for another four cycles at the same dose level. |
Drug: GNC-038
Administration by intravenous infusion.
|
Outcome Measures
Primary Outcome Measures
- Dose limiting toxicity (DLT) [Up to 14 days after the first dose of GNC-038]
- Maximum tolerated dose (MTD) or maximum administrated dose (MAD) [Up to 14 days after the first dose of GNC-038]
- Treatment-Emergent Adverse Event (TEAE) [Up to approximately 24 months]
- The recommended dose for future clinical study [Up to 14 days after the first dose of GNC-038]
Secondary Outcome Measures
- Adverse Events of special interest (AESI) [Up to approximately 24 months]
- Cmax: Maximum serum concentration of GNC-038 [Up to 14 days after the first dose of GNC-038]
- Css: Concentration of GNC-038 at steady state plateau [Up to 14 days after the first dose of GNC-038]
- Tmax: Time to maximum serum concentration (Tmax) of GNC-038 [Up to 14 days after the first dose of GNC-038]
- T1/2: Half-life of GNC-038 [Up to 14 days after the first dose of GNC-038]
- AUC0-inf: Area under the serum concentration-time curve from time 0 to infinity [Up to 14 days after the first dose of GNC-038]
- AUC0-t: Area under the serum concentration-time curve from time 0 to the time of the last measurable concentration [Up to 14 days after the first dose of GNC-038]
- CL: Clearance in the serum of GNC-038 per unit of time [Up to 14 days after the first dose of GNC-038]
- Incidence and titer of ADA (Anti-drug antibody) [Up to approximately 24 months]
- Incidence and titer of Nab (Neutralizing antibody) [Up to approximately 24 months]
- ORR (Objective Response Rate ) [Up to approximately 24 months]
- DCR (Disease Control Rate) [Up to approximately 24 months]
- PFS (Progression-free Survival) [Up to approximately 24 months]
- DOR (Duration of Response) [Up to approximately 24 months]
Eligibility Criteria
Criteria
Inclusion Criteria:
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The participants could understand and sign the informed consent form, and must participate voluntarily.
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No gender limit;
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Age: ≥18 years old
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Expected survival time ≥ 3 months.
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Has suffered from Non-Hodgkin lymphoma confirmed by histology or cytology.
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Those who have recurrent or refractory Non-Hodgkin lymphoma, including:
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Participants with first recurrence and progress during second-line treatment;
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Participants with recurrence after second-line or multi-line treatment;
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Refractory participants referred to those with no remission or progression after full dose and full cycle use of standard or current clinically commonly selected combination treatment regimens, and those with no remission or progression after replacement of second-line regimens;
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Recurrent or refractory participants that are, determined by the investigators, not applicable/tolerated to other treatments.
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For non-Hodgkin's lymphoma, there are measurable lesions during the screening period (any long diameter of lymph node lesions ≥ 1.5 cm or any long diameter of extra-nodal lesions greater than 1.0 cm); CLL/SLL: peripheral blood leukemia cells ≥5.0×109/L; One length diameter of lymph node lesions ≥1.5cm; WM: IgM﹥2×ULN.
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Physical fitness score ECOG≤2 points.
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The toxicity of the previous anti-tumor therapy has been restored to the level ≤1 defined by NCI-CTCAE v5.0 (except for hair loss).
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The organ function within 7 days prior to the first administration meets the following requirements:
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Bone marrow function: In the case of no blood transfusion, no use of G-CSF (no use of long-acting whitening needles within 2 weeks) and drug correction within 7 days prior to screening, the absolute value of neutrophil count (ANC) ≥1.0×109/L (participants with bone marrow infiltration ≥0.5×109/L); Hemoglobin ≥80 g/L (for participants with bone marrow infiltration, ≥70 g/L); Platelet count ≥50×109/L.
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Liver function: In the absence of hepatoprotective drugs for correction within 7 days prior to screening, total bilirubin (TBIL) ≤ 1.5 ULN (TBIL ≤3 ULN in participants with Gilbert's syndrome), transaminase (AST/ALT) ≤ 2.5 ULN (participants with tumor infiltration in the liver ≤5.0 ULN), and/or alkaline phosphatase (AP) ≤5 ULN.
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Kidney function: creatinine (Cr) ≤ 1.5 ULN and creatinine clearance (Ccr) ≥ 50 mL/min (calculated by the research center).
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Coagulation function: fibrinogen (FIB) ≥1.0g/L; activated partial thromboplastin time (APTT) ≤1.5×ULN; prothrombin time (PT) ≤1.5×ULN.
- Female participants with fertility or male participants whose partner(s) are fertile must take effective contraceptive measures from 7 days prior to the first administration to 24 weeks after the administration. Female participants with fertility must have a negative serum/urine pregnancy test in 7 days prior to the first dose.
Exclusion Criteria:
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Has received live virus vaccines (including live attenuated vaccines) within 28 days prior to GNC-038 treatment.
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Has undergone major surgery within 28 days prior to the administration of this study, or planned to undergo major surgery during the study period (except for surgery such as puncture or lymph node biopsy).
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Has grade 3 or above lung disease defined according to NCI-CTCAE v5.0, including resting dyspnea, or requiring continuous oxygen therapy, or a history of interstitial lung disease (ILD).
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Severe systemic infections occurred within 4 weeks prior to screening, including but not limited to severe pneumonia, bacteremia, or severe infection complications caused by fungi, bacteria, and viruses.
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Participants at risk of active autoimmune diseases, or with a history of autoimmune diseases, including but not limited to Crohn's disease, ulcerative colitis, systemic lupus erythematosus, sarcoidosis, Wegener syndrome (polyangiitis granuloma Disease, Graves' disease, rheumatoid arthritis, pituitary inflammation, uveitis), autoimmune hepatitis, systemic sclerosis, Hashimoto' s thyroiditis, autoimmune vasculitis, autoimmune neuropathy (Guillain-Barré syndrome), etc. Except for the following conditions: Type I diabetes, hormone replacement therapy for stable hypothyroidism (including hypothyroidism caused by autoimmune thyroid disease), psoriasis or vitiligo that does not require systemic treatment.
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Complicated with other malignant tumors within 5 years prior to GNC-038 treatment, except for cured skin squamous cell carcinoma, basal cell carcinoma, superficial bladder cancer, prostate/cervix/breast carcinoma in situ (only phase Ib).
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HBsAg or HBcAb positive and HBV-DNA test ≥ULN; HCV antibody positive and HCV-RNA≥ULN; HIV antibody positive.
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Participants with poorly controlled hypertension by antihypertensive drugs (systolic blood pressure>150 mmHg or diastolic blood pressure>100 mmHg).
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Left ventricular ejection fraction ≤45%, (hypersensitivity) troponin>ULN.
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History of severe heart disease:
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New York Heart Association (NYHA) grade III or IV congestive heart failure;
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Have had myocardial infarction, bypass or stent surgery within 6 months prior to administration;
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Other heart diseases that the investigator judges are not suitable for including in the group.
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Participants with prolonged QT interval (male QTc> 450 msec or female QTc> 470 msec), complete left bundle branch block, III grade atrioventricular block.
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Has a history of allergies to recombinant humanized antibodies or human-mouse chimeric antibodies or any of the components of SI-B003.
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Pregnant or breastfeeding women.
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Other conditions that the investigator believes that it is not suitable for participating in this clinical trial.
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Has suffered from or accompanied by central nervous system diseases, including but not limited to: epilepsy, paralysis, stroke, severe brain injury, Alzheimer's, Parkinson's disease, cerebellar disease, cerebral organic syndrome, and psychosis.
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There is an invasion of the central nervous system.
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Has accepted organ transplantation or allogeneic hematopoietic stem cell transplantation (ALLo-HSCT).
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Has accepted autologous hematopoietic stem cell transplantation (Auto-HSCT) within 12 weeks prior to GNC-038 treatment.
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Currently using immunosuppressive agents within 2 weeks prior to GNC-038 treatment, including but not limited to: Cyclosporine, tacrolimus, etc.; receiving high-dose glucocorticoids within 2 weeks prior to GNC-038 treatment (longer than 14 days, a stable dose of >30 mg of prednisone or other glucocorticoids at the same dose per day).
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Has received radiotherapy within 4 weeks prior to GNC-038 treatment.
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Has received anti-CD20 or anti-CD79b treatment within 4 weeks prior to GNC-038 treatment, and has received chemotherapy, small molecule targeted drugs and anti-tumor traditional Chinese medicine within 2 weeks prior to GNC-038 treatment.
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Has received CAR-T treatment within 12 weeks prior to GNC-038 treatment.
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Has participated in any other clinical trials within 4 weeks prior to GNC-038 treatment.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Hematology Hospital, Institute of Hematology, Chinese Academy of Medical Sciences | Tianjin | Tianjin | China | 300020 |
Sponsors and Collaborators
- Sichuan Baili Pharmaceutical Co., Ltd.
- SystImmune Inc.
Investigators
- Principal Investigator: Jianxiang Wang, Hematology Hospital, Institute of Hematology, Chinese Academy of Medical Sciences
- Principal Investigator: Junyuan Qi, Hematology Hospital, Institute of Hematology, Chinese Academy of Medical Sciences
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- GNC-038-101