ATIM-16. NIVOLUMAB COMBINED WITH RADIOTHERAPY WITH OR WITHOUT TEMOZOLOMIDE IN PATIENTS WITH NEWLY DIAGNOSED GLIOBLASTOMA: RESULTS FROM PHASE 1 SAFETY COHORTS IN CHECKMATE 143

Abstract

BACKGROUND: Patients with glioblastoma have a poor prognosis, with 5-year survival rates <5%. Nivolumab is an IgG4 monoclonal antibody inhibitor of programmed death 1 (PD-1) receptor with demonstrated efficacy in multiple cancer types. In phase 1 cohorts 1c and 1d of CheckMate 143 (NCT02017717), the safety and tolerability of nivolumab with radiotherapy ± temozolomide was evaluated in patients with newly diagnosed glioblastoma.METHODS: Following surgery, patients in cohort 1c received nivolumab 3 mg/kg Q2W with standard radiotherapy and temozolomide concurrently (75 mg/m2 daily), and then with adjuvant temozolomide (150–200 mg/m2 for 5 days/28 days for ≥6 cycles). Cohort 1d patients had unmethylated MGMT and received nivolumab 3 mg/kg Q2W with radiotherapy and no temozolomide. Nivolumab was continued Q2W for patients in both cohorts until progression/unacceptable toxicity.RESULTS: Most patients (61%) in cohorts 1c (n=31) and 1d (n=26) had measurable disease at enrollment. In cohort 1c, 39% and 52% of patients had methylated and unmethylated MGMT promoters, respectively. To date (cutoff, 3/23/2016), treatment has been well tolerated. Treatment discontinuation in cohorts 1c (26%) and 1d (35%) was due primarily to radiographic progression (1c, 10%; 1d, 35%) and withdrawn consent (1c, 10%). Most frequent treatment-related adverse events (AEs) included fatigue (1c, 1d: 26%, 23%), headache (23%, 8%), and increased AST (23%, 0%). Treatment-related serious AEs reported in ≥2 patients were pneumonia (6%, 0%), pyrexia (6%, 0%) and tumor flare (3%, 8%), characterizing either disease progression or pseudoprogression. AEs leading to discontinuation were increased aminotransferases (n=2 [1c]). No toxic deaths have been reported.CONCLUSIONS: This is the first prospective clinical trial investigating nivolumab in newly diagnosed glioblastoma. Results suggest that the combination of nivolumab with radiotherapy ± temozolomide is feasible and well tolerated, raising no new safety concerns. These data support continued clinical investigation in this population. Updated efficacy results will be presented