An Open-Label, Multi-Center, Phase I Study to Evaluate the Safety, Tolerability，Pharmacokinetic/Pharmacodynamics and Anti-tumor Activity of Tetra-specific Antibody GNC-039 in Participants With Relapsed/Refractory or Metastatic Solid Tumors

Sichuan Baili Pharmaceutical Co., Ltd.6 sites in 1 country60 target enrollmentApril 14, 2021

ConditionsRecurrent Glioma Solid Tumor

InterventionsGNC-039

Overview

Phase: Phase 1
Intervention: GNC-039
Conditions: Recurrent Glioma
Sponsor: Sichuan Baili Pharmaceutical Co., Ltd.
Enrollment: 60
Locations: 6
Primary Endpoint: Dose limiting toxicity (DLT)
Status: Recruiting
Last Updated: 7 months ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

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.

Registry

clinicaltrials.gov

Start Date

April 14, 2021

End Date

December 1, 2026

Last Updated

7 months ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Sichuan Baili Pharmaceutical Co., Ltd.

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•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.
•No gender limitation.
•Age: ≥18 years old.
•KPS≥60 points.
•The expected survival as determined by the researchers was ≥3 months.
•Hematological functions meet the following requirements: neutrophil absolute count (ANC) ≥1.5×109/L, platelet count ≥75×109/L, hemoglobin ≥90g/L.
•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).
•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).
•Coagulation function: fibrinogen ≥1.5g/L; Activated partial thromboplastin time (APTT) ≤1.5×ULN; Prothrombin time (PT) ≤1.5×ULN.
•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.

Exclusion Criteria

•Patients who are allergic to immunoglobulin or any component of the injectable formulation of GNC-
•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.
•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).
•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.).
•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.
•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).
•Previous organ transplant recipients.
•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.
•Thrombotic events such as deep vein thrombosis, arterial thrombosis, and pulmonary embolism occurred within 6 months prior to screening.
•Other conditions deemed unsuitable for participation in this clinical trial by the investigator.

Arms & Interventions

Study treatment

After the completion of the first cycle of treatment, if the patient has no intolerable toxic side effects during the first cycle of treatment, the investigator can communicate with the patient whether to continue the treatment during the 2-8 cycle.

Intervention: GNC-039

Outcomes

Primary Outcomes

Dose limiting toxicity (DLT)

Time Frame: Up to 14 days after the first dose of GNC-039

DLTs are assessed according to NCI-CTCAE v5.0 during the first cycle and defined as occurrence of any of the toxicities in DLT definition if judged by the investigator to be possibly, probably or definitely related to study drug administration.

Maximum tolerated dose (MTD) or maximum administrated dose (MAD)

Time Frame: Up to 14 days after the first dose of GNC-039

In the dose increment stage, the highest dose whose estimated DLT rate is closest to the target DLT rate but does not exceed the upper bound of the equivalent interval of DLT rate is selected as MTD.

Treatment-Emergent Adverse Event (TEAE)

Time Frame: Up to approximately 24 months

The incidence and severity of adverse events (TEAE) during treatment were graded according to the National Cancer Institute Standard for Common Terminology for Adverse Events (NCI-CTCAE, v5.0).

Secondary Outcomes

Drug-related Adverse Events(Up to approximately 24 months)
Cmax: Maximum serum concentration of GNC-039(Up to 14 days after the first dose of GNC-039)
T1/2: Half-life of GNC-039(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(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(Up to 14 days after the first dose of GNC-039)
CL: Clearance in the serum of GNC-039 per unit of time(Up to 14 days after the first dose of GNC-039)
Incidence and titer of ADA (Anti-drug antibody)(Up to approximately 24 months)
ORR (Objective Response Rate )(Up to approximately 24 months)
OS (Overall Survival)(Up to approximately 24 months)
PFS (Progression-free Survival)(Up to approximately 24 months)
Tmax: Time to maximum serum concentration (Tmax) of GNC-039(Up to 14 days after the first dose of GNC-039)
DOR (Duration of Response)(Up to approximately 24 months)