A randomised phase II multicentre study of ipilimumab with temozolomide vs temozolomide alone after surgery and chemoradiotherapy in patients with recently diagnosed glioblastoma: Ipi-Glio.

LBA2023 Background: Median survival for patients with glioblastoma is less than a year. Standard treatment comprises surgical debulking if feasible followed by temozolomide (TMZ) chemoradiotherapy. The objective of this clinical trial is to evaluate whether the addition of the CTLA-4 immune checkpoint inhibitor ipilimumab (IPI) improves survival. Methods: Ipi-Glio is an academic phase II, open label, stratified randomised multicentre study of IPI + TMZ (Arm A) vs TMZ alone (Arm B), after surgery and radical radiotherapy with concomitant temozolomide in patients with recently diagnosed de-novo glioblastoma. Following completion of chemoRT, patients were randomised 2:1 Arm A:B, with stratification to extent of surgery and MGMT promotor methylation. IPI 3mg/kg was administered q3/52 for 4 cycles, and TMZ 150-200mg/m2 days 1-5 q4/52 for 6 cycles. Primary outcome was overall survival (OS), treatment difference reported as hazard ratio (HR) with 60% confidence intervals (CI) and OS at 18 months. Secondary outcomes were progression-free Survival (PFS) and safety. Results: 119 patients were randomly assigned, 79 to Arm A and 40 to Arm B, at seven centres in the UK between Jan 2019 and April 2021. Patient characteristics (Arm A vs B): median Age 53 vs 48 years; male sex 70% vs 65%; ECOG PS0 70 vs 70%, PS1 30 vs 30%; MGMT promotor methylation 39% vs 40%; IDH mutation 11% vs 10%; surgical gross total resection 61% vs 60%. PFS (Arm A vs B): median PFS 10.9 months (m) vs 12.5mo, HR 1.252 (60%CI 1.01-1.54, p=0.369); 18m PFS 22% (60%CI 17-27%) vs 43% (34-51%). Overall Survival (Arm A vs B): median OS 22.7 vs 26.4 months, HR 1.223 (60% CI 0.986-1.516, p=0.431); 18 month OS 53% (60%CI 48-58%) vs 64% (56-70%). Adverse events (AE) reported by CTCAE grade (Arm A vs B): total reported AEs 1058 vs 329; no. of reported AEs per patient: mean 13.5 (SD 10.1) vs mean 8.2 (SD 7.3). Conclusions: No improvement in PFS or OS was observed with the addition of ipilimumab to temozolomide. This study does not support further investigation of this regimen in this setting. Clinical trial information: ISRCTN84434175 .