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

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 ( = 15, methylated/unknown promoter; = 16, unmethylated promoter) received nivolumab and RT+TMZ (NIVO+RT+TMZ) and 30 patients with unmethylated promoter received NIVO+RT. In part B (expansion), patients with unmethylated promoter were randomized to NIVO+RT+TMZ ( = 29) or NIVO+RT ( = 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 promoter. In patients with unmethylated 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 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 promoter, and differences by methylation status were observed.