Inclusion Criteria:
1. After failure of standard treatment (surgery, stupp regimen), subjects with
diagnosed recurrent high-grade glioma (WHO Grade III-IV), or other
recurrent/refractory or metastatic solid tumors can understand the informed consent,
voluntarily participate in and sign the informed consent.
2. No gender limitation.
3. Age: ≥18 years old.
4. KPS≥60 points.
5. The expected survival as determined by the researchers was ≥3 months.
6. Hematological functions meet the following requirements: neutrophil absolute count
(ANC) ≥1.5×109/L, platelet count ≥75×109/L, hemoglobin ≥90g/L.
7. Renal function meets the following requirements: creatinine (Cr) ≤1.5 ULN and
creatinine clearance (Ccr) ≥50 mL/min (based on the calculation criteria of the
study center), urinary protein ≤2+ or < 1000mg/24h (urine).
8. Liver functions meet the following requirements: Aspartate aminotransferase (AST)
and alanine aminotransferase (ALT) ≤3.0×ULN; Total bilirubin ≤1.5×ULN (Gilbert's
syndrome ≤3×ULN).
9. Coagulation function: fibrinogen ≥1.5g/L; Activated partial thromboplastin time
(APTT) ≤1.5×ULN; Prothrombin time (PT) ≤1.5×ULN.
10. A fertile female subject or a fertile male subject with a fertile partner must use
highly effective contraception from the date of informed consent until 12 weeks
after the last dosing. Serum pregnancy tests must be negative for fertile female
subjects within -10 to -3 days prior to initial dosing.
11. Subject is able and willing to comply with visits, treatment plans, laboratory
tests, and other study-related procedures as specified in the study protocol.
12. For glioma patients: a. There must be a pathological diagnosis and a definite
diagnosis of high-grade glioma; b. MRI diagnosis supported recurrence; c. Presence
of at least one measurable tumor lesion according to RANO criteria; Or subjects
receiving surgical treatment after recurrence; d. Archived primary or recurrent
tumor tissue or sections that can be submitted to the Center for review (no less
than 10 pathological white slices of 3-5μm or corresponding tissue blocks should be
provided). If patients are unable to provide tumor tissue specimens, the Center may
inform the sponsor and enroll them.
13. For patients with other solid tumors: a. Histologically or cytologically confirmed
recurrent/refractory or metastatic solid tumors with disease progression confirmed
by imaging or other objective evidence after standard treatment; Or subjects with
refractory solid tumors who cannot tolerate standard therapy or have
contraindications to standard therapy; b. Must have at least one measurable lesion
that meets the RECIST v1.1 definition.
Exclusion Criteria:
1. Patients who are allergic to immunoglobulin or any component of the injectable
formulation of GNC-039.
2. Patients with active infections requiring intravenous antibiotics who did not
complete treatment 1 week prior to enrollment, except those who received
prophylactic antibiotics for puncture or biopsy.
3. Human immunodeficiency virus antibody (HIVAb) positive, active tuberculosis, active
hepatitis B virus infection (HBsAg positive or HBcAb positive with HBV-DNA copy
number ≥ULN) or hepatitis C virus infection (HCV-RNA≥ULN).
4. Toxicity from prior antitumor therapy did not decrease to ≤ grade 1 as defined in
CTCAE version 5.0 (except for toxicities that the investigators judged to be of no
safety risk, such as alopecia, grade 2 peripheral neurotoxicity, stable
hypothyroidism after hormone replacement therapy, etc.).
5. Patients at risk for active autoimmune diseases, or with a history of autoimmune
diseases that may involve the central nervous system, Including but not limited to
Crohn's disease, ulcerative colitis, systemic lupus erythematosus, Wegener syndrome,
autoimmune hepatitis, systemic sclerosis, Hashimoto's thyroiditis, autoimmune
vasculitis, autoimmune neuropathy (Guillain-Barre syndrome), etc. Exceptions include
type I diabetes mellitus, hypothyroidism stable on hormone replacement therapy
(including hypothyroidism caused by autoimmune thyroid disease), psoriasis or
vitiligo that do not require systemic therapy, and autoimmune diseases caused by B
cells and anti-autoimmune antibodies.
6. Lung disease defined by NCI-CTCAE v5.0 as ≥ grade 3, including patients with resting
dyspnea, or in need of continuous oxygen therapy, or with a history of interstitial
lung disease (ILD).
7. Previous organ transplant recipients.
8. History of severe cardiovascular and cerebrovascular diseases, including but not
limited to: severe cardiac rhythm or conduction abnormalities, such as ventricular
arrhythmia requiring clinical intervention, degree III atrioventricular block, etc.;
At rest, the QT interval was prolonged (QTc > 450 msec in men or 470 msec in women);
Acute coronary syndrome, congestive heart failure, aortic dissection, stroke, or
other grade 3 or higher cardiovascular and cerebrovascular events occurred within 6
months prior to initial administration; There is heart failure ≥II on the New York
Heart Association (NYHA) cardiac function scale.
9. Thrombotic events such as deep vein thrombosis, arterial thrombosis, and pulmonary
embolism occurred within 6 months prior to screening.
10. Other conditions deemed unsuitable for participation in this clinical trial by the
investigator.
11. Brain gliomas: a. Patients who underwent surgery, chemotherapy, targeted and
immunotherapy, iodine in vivo radiation, radiation therapy, or planned to undergo
radiation therapy during the trial within 4 weeks of enrollment or 5 half-lives,
whichever is shorter; b. Patients who had received intracranial lesion puncture
biopsy within 7 days prior to enrollment; c. Received other investigational drugs or
treatments that are not on the market within 4 weeks prior to enrollment; d. There
was a history of central nervous system bleeding/infarction not associated with
antineoplastic agents, such as stroke or intracranial and ocular bleeding (including
embolic stroke), during the 6 months prior to enrollment.
12. For other solid tumors: a. Received chemotherapy, antibody therapy,
molecular-targeted therapy, or investigational drugs within 4 weeks or 5 half-lives
(whichever is shorter) of initial administration; b. Patients who underwent major
surgery within 28 days prior to administration of the drug or were scheduled to
undergo major surgery during the study period (except for procedures such as
puncture or lymph node biopsy); c. poorly controlled hypertension (systolic blood
pressure > 150 mmHg or diastolic blood pressure > 100 mmHg); d. Previous or
associated central nervous system lesions, including but not limited to: paralysis,
stroke (except those with lacunar infarction indicated by imaging examination but
without treatment), severe brain injury, senile dementia, Parkinson's disease,
organic brain syndrome, and psychosis; e. Received other investigational drugs or
treatments that were not on the market within 4 weeks prior to enrollment.
