A phase 2, open label, clinical trial of pre-surgical and adjuvant treatment of recurrent glioblastoma with tremelimumab and durvalumab alone and in combination.

PURPOSE: Survival is poor for patients with recurrent glioblastoma. We prospectively investigated the use of tremelimumab (CTLA-4 inhibitor) and durvalumab (PD-L1 inhibitor) given pre- and post-surgery to assess clinical activity and safety, and to understand the intratumoral immunologic changes. This report focuses on clinical outcomes. METHODS: Recurrent glioblastoma patients were randomized to either: Arm 1, tremelimumab (75 mg every 4 weeks IV); Arm 2, durvalumab (750 mg every 2 weeks); or Arm 3, combination (tremelimumab 75 mg every 4 weeks for 7 doses then every 12 weeks along with durvalumab 750 mg every 2 weeks). Eligible patients received treatment 14 days prior to surgery, then underwent clinically indicated resection, followed by adjuvant treatment starting within 28 days after surgery. RESULTS: Thirty-one patients were evaluable. Median OS and PFS for the entire cohort was 8.9 months (95% CI, 7.5–14.2) and 3.2 months (95% CI, 3.0-4.1), respectively. Median OS for Arm 1 was 7.5 months (95% CI, 2.3–14.7), 13.2 for Arm 2 (95% CI, 2.6–28.0), and 7.9 (95% CI, 4.8–14.2; P = 0.33) for Arm 3. Treatment was well tolerated. One patient developed grade 3 colitis while 2 patients had grade 2 dermatitis. Ten patients had grade 3 hypertension, 4 patients had grade 3 hyperglycemia, and 2 patients had wound complications. There were no treatment related deaths or severe immune related toxicities. CONCLUSION: The combination of tremelimumab and durvalumab is safe in recurrent glioblastoma though there was no statistical improvement in survival. This data aligns with prior studies showing a lack of benefit with checkpoint inhibitors. TRAIL REGISTRATION : ClinicalTrials.Gov Registration NCT02794883. Registration Date 6/9/2016.