Abstract INTRODUCTION Glioblastoma (GBM) is the most common primary central nervous system malignancy. There is poor long-term survival with a median survival of two years and little consensus on second line therapies after progression. APG-157 is a new class of botanical drugs developed under FDA’s Botanical Drugs Guidance. The purpose of this study is to assess the safety and effect of APG-157 on the six-month survival and quality of life (QoL) of patients with recurrent GBM. METHODS Approval was obtained from the Baylor Scott and White IRB (# 022-230, Approval number 58100462000) and under group expanded access protocol (IND 162339). Major inclusion criteria include histologically proven GBM and unequivocal tumor progression 12 weeks after completion of standard first-line therapy. APG-157 was administered either as monotherapy or in combination with temozolomide or tumor-treating fields. Adverse events were assessed at each study visit. Patient data were collected from study conception through April 25, 2023. RESULTS A total of 6 patients (3 male, 3 females) were treated (median age was 54). A median of 2 treatment cycles were administered. 2 Patients withdrew from the study voluntarily, 2 patients expired while on treatment, and 2 patients continued treatment at the time of data analysis. 47.4% (9/19) of the questionnaire time points were completed, however, we saw low QoL (EORTC-QLQ-C30 and EORTC-QLQ-BN20) with a mean global health status score of 4.5. No patient saw a significant increase in their symptoms and one patient reported a 6-point decrease in their neurological symptoms. One patient who was on monotherapy of APG-157 for two months showed stable disease by MRI evaluation. There were no reported adverse events from the study medication. CONCLUSION Future follow-up and a larger sample size are necessary to confirm the impact of APG-157 on six-month survival and QoL.