Nivolumab plus radiotherapy with or without temozolomide in newly diagnosed glioblastoma: Results from exploratory phase I cohorts of CheckMate 143

Antonio Omuro; David A Reardon; John H Sampson; Joachim Baehring; Solmaz Sahebjam; Timothy F Cloughesy; Alexandros-Georgios Chalamandaris; Von Potter; Nicholas Butowski; Michael Lim

doi:10.1093/noajnl/vdac025

Nivolumab plus radiotherapy with or without temozolomide in newly diagnosed glioblastoma: Results from exploratory phase I cohorts of CheckMate 143

Neurooncol Adv. 2022 Feb 26;4(1):vdac025. doi: 10.1093/noajnl/vdac025. eCollection 2022 Jan-Dec.

Authors

Affiliations

¹ Department of Neurology, Yale School of Medicine, New Haven, Connecticut, USA.
² Department of Neurology, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
³ Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA.
⁴ Department of Neurosurgery, Duke University Hospital, Durham, North Carolina, USA.
⁵ Moffitt Cancer Center, University of South Florida, Tampa, Florida, USA.
⁶ Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, USA.
⁷ Biostatistics, Bristol Myers Squibb, Braine-L'Alleud, Belgium.
⁸ Clinical Development, Bristol Myers Squibb, Princeton, New Jersey, USA.
⁹ Department of Neurological Surgery, University of California, San Francisco, San Francisco, California, USA.
¹⁰ Department of Neurosurgery, The Johns Hopkins Hospital, Baltimore, Maryland, USA.

Abstract

Background: The phase 1 cohorts (1c+1d) of CheckMate 143 (NCT02017717) evaluated the safety/tolerability and efficacy of nivolumab plus radiotherapy (RT) ± temozolomide (TMZ) in newly diagnosed glioblastoma.

Methods: In total, 136 patients were enrolled. In part A (safety lead-in), 31 patients (n = 15, methylated/unknown MGMT promoter; n = 16, unmethylated MGMT promoter) received nivolumab and RT+TMZ (NIVO+RT+TMZ) and 30 patients with unmethylated MGMT promoter received NIVO+RT. In part B (expansion), patients with unmethylated MGMT promoter were randomized to NIVO+RT+TMZ (n = 29) or NIVO+RT (n = 30). Primary endpoint was safety/tolerability; secondary endpoint was overall survival (OS).

Results: NIVO+RT±TMZ was tolerable; grade 3/4 treatment-related adverse events occurred in 51.6% (NIVO+RT+TMZ) and 30.0% (NIVO+RT) of patients in part A and 46.4% (NIVO+RT+TMZ) and 28.6% (NIVO+RT) in part B. No new safety signals were detected. In part A, median OS (mOS) with NIVO+RT+TMZ was 33.38 months (95% CI, 16.2 to not estimable) in patients with methylated MGMT promoter. In patients with unmethylated MGMT promoter, mOS was 16.49 months (12.94-22.08) with NIVO+RT+TMZ and 14.41 months (12.55-17.31) with NIVO+RT. In part B, mOS was 14.75 months (10.01-18.6) with NIVO+RT+TMZ and 13.96 months (10.81-18.14) with NIVO+RT in patients with unmethylated MGMT promoter.

Conclusions: CheckMate 143 was the first trial evaluating immune checkpoint inhibition with first-line treatment of glioblastoma. Results showed that NIVO can be safely combined with RT±TMZ, with no new safety signals. Toxicities, including lymphopenia, were more frequent with NIVO+RT+TMZ. OS was similar with or without TMZ in patients with unmethylated MGMT promoter, and differences by MGMT methylation status were observed.

Keywords: PD-1; newly diagnosed glioblastoma; nivolumab; radiotherapy; temozolomide.

Abstract

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