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.
Mulholland PJ., Brown NF., McBain C., Brazil L., Peoples S., Jefferies S., Harris F., Plaha P., Vinayan A., Brooks C., Hussain S., Dutton SJ., Ng S., Levy S., Coutts T.
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 .