Clinical safety, tolerability and preliminary efficacy of injection and liposomal honokiol treatment in patients with recurrent high-grade glioma (Preprint)
Authors: Li Wenbin , Wang Ce , Lai XinTian , Li Baolin 
Published: October 2024

BACKGROUND

OBJECTIVE: To observe the clinical safety, tolerability, pharmacokinetics and preliminary efficacy of lipo-HK for injection as a monotherapy in patients with recurrent high-grade glioma and to provide the basis for drug dose and method of administration.
Methods: Patients with recurrent high-grade glioma were screened according to inclusion and exclusion criteria. A total of 5 experimental dose groups were included. The initial dose was 80 mg, and the dose was escalated according to the modified Fisher method, and the highest dose was 420 mg. Each patient received only one dose of administration. This clinical trial consists of two phases - a dose escalation phase and a dose expansion phase. The dose escalation phase includes a single-dose period (1 day of single dose, followed by three days of observation), multiple-dose period (5 days of continuous dosing per week, two days off, three weeks, one week off) and multiple-dose extension periods (3 weeks of multiple doses, one week of rest, then three weeks of additional doses, each week for five consecutive days and two days off). The dose-expansion phase consists of single-dose period and multiple-dose period. If the patient tolerates during the single-dose period, they could enter the multiple-dose period. If the patient gets clinical benefits from HK under clinical evaluation after the multiple dosing period, the patient could enter the multiple extended dosing period. Clinical safety was assessed using NCI CTCAE 4.03 criteria, and RANO criteria were used to evaluate the efficacy.
Results: A total of 24 patients were enrolled in this clinical study. The clinical symptoms of many subjects improved after the drug was administered, and the clinical effects of 10 subjects were evaluated as "Stable disease" after multiple administration periods.Long-term use is well tolerated by patients.
Conclusion: lipo-HK for injection is clinically safe and well tolerated in the treatment of patients with recurrent high-grade glioma. The recommended dose for subsequent studies is 420 mg.

OBJECTIVE

To observe the clinical safety, tolerability, pharmacokinetics and preliminary efficacy of lipo-HK for injection as a monotherapy in patients with recurrent high-grade glioma and to provide the basis for drug dose and method of administration.

METHODS

Patients with recurrent high-grade glioma were screened according to inclusion and exclusion criteria. A total of 5 experimental dose groups were included. The initial dose was 80 mg, and the dose was escalated according to the modified Fisher method, and the highest dose was 420 mg. Each patient received only one dose of administration. This clinical trial consists of two phases - a dose escalation phase and a dose expansion phase. The dose escalation phase includes a single-dose period (1 day of single dose, followed by three days of observation), multiple-dose period (5 days of continuous dosing per week, two days off, three weeks, one week off) and multiple-dose extension periods (3 weeks of multiple doses, one week of rest, then three weeks of additional doses, each week for five consecutive days and two days off). The dose-expansion phase consists of single-dose period and multiple-dose period. If the patient tolerates during the single-dose period, they could enter the multiple-dose period. If the patient gets clinical benefits from HK under clinical evaluation after the multiple dosing period, the patient could enter the multiple extended dosing period. Clinical safety was assessed using NCI CTCAE 4.03 criteria, and RANO criteria were used to evaluate the efficacy.

RESULTS

A total of 24 patients were enrolled in this clinical study. The clinical symptoms of many subjects improved after the drug was administered, and the clinical effects of 10 subjects were evaluated as "Stable disease" after multiple administration periods.Long-term use is well tolerated by patients.

CONCLUSIONS

lipo-HK for injection is clinically safe and well tolerated in the treatment of patients with recurrent high-grade glioma. The recommended dose for subsequent studies is 420 mg.