Nivolumab with or without ipilimumab in patients with recurrent glioblastoma: Results from exploratory phase i cohorts of CheckMate 143

Antonio Omuro, Gordana Vlahovic, Michael Lim, Solmaz Sahebjam, Joachim Baehring, Timothy Cloughesy, Alfredo Voloschin, Shakti H. Ramkissoon, Keith L. Ligon, Robert Latek, Ricardo Zwirtes, Lewis Strauss, Prashni Paliwal, Christopher T. Harbison, David A. Reardon, John H. Sampson

Research output: Contribution to journalArticlepeer-review

Abstract

Background Immunotherapies have demonstrated efficacy across a diverse set of tumors supporting further evaluation in glioblastoma. The objective of this study was to evaluate the safety/tolerability and describe immune-mediated effects of nivolumab ± ipilimumab in patients with recurrent glioblastoma. Exploratory efficacy outcomes are also reported. Methods Patients were randomized to receive nivolumab 3 mg/kg every 2 weeks (Q2W; NIVO3) or nivolumab 1 mg/kg + ipilimumab 3 mg/kg every 3 weeks (Q3W) for 4 doses, then nivolumab 3 mg/kg Q2W (NIVO1+IPI3). An alternative regimen of nivolumab 3 mg/kg + ipilimumab 1 mg/kg Q3W for 4 doses, then nivolumab 3 mg/kg Q2W (NIVO3+IPI1) was investigated in a nonrandomized arm. Results Forty patients were enrolled (NIVO3, n = 10; NIVO1+IPI3, n = 10; NIVO3+IPI1, n = 20). The most common treatment-related adverse events (AEs) were fatigue (NIVO3, 30%; NIVO1+IPI3, 80%; NIVO3+IPI1, 55%) and diarrhea (10%, 70%, 30%, respectively). AEs leading to discontinuation occurred in 10% (NIVO3), 30% (NIVO1+IPI3), and 20% (NIVO3+IPI1) of patients. Three patients achieved a partial response (NIVO3, n = 1; NIVO3+IPI1, n = 2) and 8 had stable disease for ≥12 weeks (NIVO3, n = 2; NIVO1+IPI3, n = 2; NIVO3+IPI1, n = 4 [Response Assessment in Neuro-Oncology criteria]). Most patients (68%) had tumor-cell programmed death ligand-1 expression ≥1%. Immune-mediated effects mimicking radiographic progression occurred in 2 patients. Conclusions Nivolumab monotherapy was better tolerated than nivolumab + ipilimumab; the tolerability of the combination was influenced by ipilimumab dose. These safety and exploratory findings merit further investigation of immunotherapies in glioblastoma.

Original languageEnglish (US)
Pages (from-to)674-686
Number of pages13
JournalNeuro-oncology
Volume20
Issue number5
DOIs
StatePublished - Apr 9 2018

Keywords

  • CheckMate 143
  • PD-L1
  • ipilimumab
  • nivolumab
  • recurrent glioblastoma

ASJC Scopus subject areas

  • Oncology
  • Clinical Neurology
  • Cancer Research

Fingerprint Dive into the research topics of 'Nivolumab with or without ipilimumab in patients with recurrent glioblastoma: Results from exploratory phase i cohorts of CheckMate 143'. Together they form a unique fingerprint.

Cite this