A Study of GNC-039, a Tetra-specific Antibody, in Participants With Relapsed/Refractory or Metastatic Solid Tumors
Study Details
Study Description
Brief Summary
In this study, the safety, tolerability and preliminary effectiveness of GNC-039 in patients with relapsed/refractory or metastatic glioma or other solid tumors 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-039.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Study treatment Patients receive GNC-039 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 two cycles at the same dose level. |
Drug: GNC-039
Administration by intravenous infusion.
|
Outcome Measures
Primary Outcome Measures
- Dose limiting toxicity (DLT) [Time Frame: Up to 14 days after the first dose of GNC-039]]
- Maximum tolerated dose (MTD) or maximum administrated dose (MAD) [Time Frame: Up to 14 days after the first dose of GNC-039]]
- Treatment-Emergent Adverse Event (TEAE) [[Time Frame: Up to approximately 24 months]]
Secondary Outcome Measures
- Drug-related Adverse Events [[Time Frame: Up to approximately 24 months]]
- Cmax: Maximum serum concentration of GNC-039 [[Time Frame: Up to 14 days after the first dose of GNC-039]]
- Tmax: Time to maximum serum concentration (Tmax) of GNC-039 [[Time Frame: Up to 14 days after the first dose of GNC-039]]
- T1/2: Half-life of GNC-039 [[Time Frame: Up to 14 days after the first dose of GNC-039]]
- AUC0-inf: Area under the serum concentration-time curve from time 0 to infinity [[Time Frame: Up to 14 days after the first dose of GNC-039]]
- AUC0-t: Area under the serum concentration-time curve from time 0 to the time of the last measurable concentration [[Time Frame: Up to 14 days after the first dose of GNC-039]]
- CL: Clearance in the serum of GNC-039 per unit of time [[Time Frame: Up to 14 days after the first dose of GNC-039]]
- Incidence and titer of ADA (Anti-drug antibody) [[Time Frame: Up to approximately 24 months]]
- ORR (Objective Response Rate ) [[Time Frame: Up to approximately 24 months]]
- OS (Overall Survival) [[Time Frame: Up to approximately 24 months]]
- PFS (Progression-free Survival) [[Time Frame: Up to approximately 24 months]]
- DOR (Duration of Response) [[Time Frame: Up to approximately 24 months]]
Eligibility Criteria
Criteria
Inclusion Criteria:
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After the failure of standard treatment (surgery, stupp regimen treatment), the recurrence of high-grade glioma (WHO grade III-IV) or other relapsed/refractory or metastatic solid tumor subjects could understand and consent form, voluntarily participate and sign the informed consent form.
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No gender limit.
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Age: ≥18 years old.
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KPS≥60 points.
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Expected survival time ≥ 3 months.
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Hematology function meets the following requirements: absolute neutrophil count (ANC) ≥1.5×109/L, platelet count ≥100×109/L, hemoglobin ≥90g/L.
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Renal function meets the following requirements: creatinine (Cr) ≤ 1.5 ULN and creatinine clearance (Ccr) ≥ 50 mL/min (calculated by the research center), urine protein ≤ 2+ or ≤ 1000 mg/24h (urine).
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Liver function meets the following requirements: aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤3×ULN; total bilirubin ≤1.5×ULN (Gilbert's syndrome ≤3×ULN).
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Coagulation function: fibrinogen ≥1.0g/L; activated partial thromboplastin time (APTT) ≤1.5×ULN; prothrombin time (PT) ≤1.5×ULN.
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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.
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The participants are capable and willing to comply with the visits, treatment plans, laboratory examinations and other research-related procedures stipulated in the research protocol.
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For participants with glioma:
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There must be a pathological diagnosis of high-grade glioma;
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MRI diagnosis supports recurrence;
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There is at least one measurable tumor lesion according to the RANO standard; or the participants undergo surgery after recurrence;
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Have archived tumor tissues or sections that could be submitted to the center for review for the first time or recurrence (no less than 10 pathological white films of 3-5μm should be provided).
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For participants with other solid tumors:
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Relapsed/refractory or metastatic solid tumor are confirmed by histology or cytology, and disease progression are confirmed by imaging or other objective evidence after receiving standard treatment; or the participants are confirmed with refractory solid tumor who cannot tolerate standard treatment or have contraindications to standard treatment;
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Must have at least one measurable lesion that meets the definition of RECIST v1.1; the participant could understand the informed consent form and sign the informed consent form voluntarily.
Exclusion Criteria:
If any of the following occurs in the participants for this study, any of them should be excluded:
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Participants who are allergic to immune globulin or any component of injection preparations.
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Participants with active infections that require intravenous antibiotics and who have not completed treatment 1 week prior to enrollment, except those who have used prophylactic antibiotics for puncture or biopsy.
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Human immunodeficiency virus antibody (HIVAb) positive, active tuberculosis, active hepatitis B virus infection (HBV-DNA copy number ≥>ULN) or hepatitis C virus (HCV) infection (HCV-RNA≥ULN).
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The toxicity of the previous anti-tumor treatment has not been reduced to the level I defined in the CTCAE 4.0 version (except for symptoms related to bone marrow suppression, such as neutropenia, anemia, thrombocytopenia) or the level specified in the inclusion criteria, except for hair loss and irreversible toxicity from previous anti-tumor treatments (defined as stable existence ≥ 2 months) permitted by the investigator/sponsor's consideration.
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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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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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Participants who have received organ transplants in the past.
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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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Participants who currently have unstable angina
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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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Previously suffering from or accompanied by deep vein thrombosis, arterial thrombosis and pulmonary embolism and other thrombotic events.
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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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For glioma participants:
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Those who have received surgery, chemotherapy, targeted and immunological drug therapy, iodine internal radiation, radiotherapy within 4 weeks prior to enrollment, or those who plan to undergo radiotherapy during the trial.
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Participants who had undergone needle biopsy of intracranial lesions within 7 days prior to enrollment
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Those who have accept other clinical trials within 4 weeks prior to enrollment
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Within 6 months prior to enrollment, there was a history of central nervous system hemorrhage/infarction unrelated to anticancer drugs, such as stroke or intraocular hemorrhage (including embolic stroke)
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For other solid tumors:
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Received anti-tumor therapy (chemotherapy, antibody therapy, molecular targeted therapy or research drug) within 14 days of the first administration or 5 half-lives (whichever is longer);
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Participants who have undergone major surgery within 28 days prior to the administration of this study, or who are planning to undergo major surgery during the study (except for surgery such as puncture or lymph node biopsy);
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Hypertension with poor drug control (systolic blood pressure> 150 mmHg or diastolic blood pressure> 100 mmHg);
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Previously suffering 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, psychosis.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Beijing Tiantan Hospital Affiliated to Capital Medical University | Beijing | Beijing | China | 100070 |
Sponsors and Collaborators
- Sichuan Baili Pharmaceutical Co., Ltd.
- SystImmune Inc.
Investigators
- Principal Investigator: Wenbin Li, Beijing Tiantan Hospital
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- GNC-039-101