Dataset Information

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

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.

SUBMITTER: Omuro A

PROVIDER: S-EPMC8989388 | biostudies-literature | 2022 Jan-Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Omuro Antonio A Reardon David A DA Sampson John H JH Baehring Joachim J Sahebjam Solmaz S Cloughesy Timothy F TF Chalamandaris Alexandros-Georgios AG Potter Von V Butowski Nicholas N Lim Michael M

Neuro-oncology advances 20220101 1

<h4>Background</h4>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.<h4>Methods</h4>In total, 136 patients were enrolled. In part A (safety lead-in), 31 patients (<i>n</i> = 15, methylated/unknown <i>MGMT</i> promoter; <i>n</i> = 16, unmethylated <i>MGMT</i> promoter) received nivolumab and RT+TMZ (NIVO+RT+TMZ) and 30 patients with unmethylated <i>MGMT ...[more]

PMID: 35402913

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Dataset Information

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

Background

Methods

Results

Conclusions

Publications

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

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