Preliminary safety and activity of nivolumab and its combination with ipilimumab in recurrent glioblastoma (GBM): CHECKMATE-143.

Abstract

3010 Background: GBM has a grim prognosis despite current first-line therapies. Immune checkpoint inhibitors have shown antitumor activity in both solid tumors and preclinical glioma models. This study evaluates the safety/tolerability of the checkpoint inhibitors nivolumab (NIVO) and ipilimumab (IPI) in patients (pts) with a first recurrence of GBM. Methods: Pts were randomized to NIVO 3 mg/kg Q2W or NIVO 1 mg/kg + IPI 3 mg/kg (NIVO+IPI) Q3W followed by NIVO 3 mg/kg Q2W. Eligible pts had first recurrence of primary GBM, no prior bevacizumab treatment and KPS ≥70. The primary endpoint was safety/tolerability. This analysis reports the preliminary experience after all pts had the opportunity to complete ≥6 months (mo) of follow-up after first dose. Results: 20 pts were treated, 10 in each arm. All pts had prior surgical resection, radiation, and temozolomide. Median age was 57 years (range: 37-73), KPS=90 (n=13), 80 (n=2) and 70 (n=5). Median time from first GBM diagnosis was 9 mo. The median number of doses (range) received in NIVO arm was 6 (3-23). In NIVO+IPI, pts received 3 (2-8) doses of NIVO and 2 (2-4) of IPI. Drug-related adverse events (AE) in ≥3 pts were fatigue (n=3) and nausea (n=3) with NIVO and fatigue (n = 8), diarrhea (n = 7), AST and lipase increased (n = 5 each), vomiting and ALT increased (n=4 each), and amylase increased, headache, hyperthyroidism, nausea and maculo-papular rash (n=3 each) with NIVO+IPI. All NIVO AEs were grade 1 or 2. Eight (80%) NIVO+IPI pts had grade 3 or 4 AEs. Drug-related AEs leading to discontinuation occurred only in NIVO+IPI pts (n = 5; 50%), including colitis, cholecystitis, diabetic ketoacidosis, confusion, and increased lipase. There were no drug-related deaths. Among 20 treated pts, OS at 6 mo. was 75%, including 7/10 NIVO pts (70%) and 8/10 NIVO+IPI pts (80%). ORR, PFS, and biomarker analysis are being evaluated. Conclusions: This is the first randomized study to report the safety/tolerability of checkpoint inhibitors in GBM. The AE profile of NIVO ± IPI was consistent with studies in other tumors. OS at 6 mo. is encouraging relative to comparable historical controls. Updated safety, efficacy, and biomarker data including on-treatment histopathology will be presented. Clinical trial information: NCT02017717.