CTIM-07. PHASE IIB RANDOMIZED, BLINDED, CONTROLLED TRIAL EVALUATING NEOADJUVANT PD-1 BLOCKADE COMBINED WITH A2B5+ GLIOMA STEM-LIKE CELL LYSATE-LOADED DCV IN RECURRENT GLIOBLASTOMA (IDH1/2 -)- TRAIL IN PROGRESS

Abstract

Abstract Our previous phase II randomized trials have determined that A2B5+ glioma stem-like cell lysate-loaded DC vaccine (GSC-DCV) demonstrates favorable safety and significantly extends the survival of glioblastoma (GBM) (NCT01567202). This study aims to investigate the clinical feasibility and efficacy of the GSC-DCV combined with aPD-1 mAbs neoadjuvant therapy in recurrent GBM (NCT04888611). GBM (IDH1/2 -) patients who had received radiotherapy and TMZ chemotherapy were enrolled in the study after pathologically confirmed recurrence. All patients received aPD-1 mAbs treatment (3mg/kg, up to 200mg) 14±5 days before surgery. Following surgery, eligible patients were randomized in a 1:1 ratio to receive either a combination treatment of aPD-1 mAbs with GSC-DCV or aPD-1 mAbs with placebo. The above-mentioned postoperative therapy was given every three weeks until disease progression or unacceptable toxicity. Besides evaluating treatment response using the iRANO criteria, MRI scans were conducted before each treatment and after surgery (in 72h) to evaluate tumor size/volume to analyze the relationship between tumor burden and prognosis. The primary endpoint of the study was overall survival, while the secondary endpoints included the evaluation of treatment-related adverse events (trAEs) and the measurement of indicators related to the immune response. From October 2021 through May 2023, a total of 22 patients were enrolled and successfully randomized. At the latest follow-up, the two groups were generally balanced with respect to baseline characteristics, encompassing age, gender, KPS, steroid use, MGMTp status, TERTp status, and tumor volume at registration. Notably, differences in survival were observed between the two groups, with respective follow-up periods ranging from 1.3 to 19.9 months and 1.0 to 12.1 months. The incidence of trAEs in all patients was 22.7%, with no grade 3 or higher trAEs observed thus far, and the main adverse event was reactive cutaneous capillary endothelial proliferation (RCCEP).