Policy & Regulation
Bristol-Myers Squibb's Phase 3 CheckMate -498 Study Did Not Meet Primary Endpoint of Overall Survival with Opdivo Plus Radiation in Patients with Newly Diagnosed MGMT-Unmethylated Glioblastoma Multiforme
13 May 2019 - - US-based pharmaceutical company Bristol-Myers Squibb Company's (NYSE: BMY) Phase 3 CheckMate -498 trial evaluating Opdivo (nivolumab) plus radiation versus temozolomide plus radiation in patients with newly diagnosed O6-methylguanine-DNA methyltransferase -unmethylated glioblastoma multiforme did not meet its primary endpoint of overall survival at final analysis, the company said.

The safety profile of Opdivo was consistent with previously reported studies in solid tumors. The company will complete a full evaluation of the data from CheckMate -498 and work with investigators on the future presentation and publication of the results.

Opdivo is also being studied in patients with newly diagnosed MGMT-methylated GBM in the Phase 3 CheckMate -548 (NCT02667587) study, in which Opdivo is added to the current standard of care, radiation plus temozolomide.

CheckMate -498 (NCT02617589) is a Phase 3 randomized, multi-centre study evaluating Opdivo and radiation versus temozolomide and radiation in patients with newly diagnosed MGMT-unmethylated GBM.

After surgery, patients in the experimental arm received Opdivo every two weeks concurrent with radiation, followed by maintenance with Opdivo every four weeks until disease progression or unacceptable toxicity.

The primary endpoint of the trial was OS. Secondary endpoints included progression-free survival, and OS rate at two years.

Glioblastoma multiforme is the most common and most aggressive type of primary malignant tumor of the central nervous system.

Globally, an estimated 300,000 patients develop, and 241,000 patients die from, brain or central nervous system cancer each year.

Standard treatment for patients with newly diagnosed GBM can include surgery followed by radiation and chemotherapy, but treatment options are limited.

The last investigational medicine to improve survival for patients with newly diagnosed GBM was approved by the US Food and Drug Administration in 2005.

The five year survival rate of patients with GBM is less than 5%.

MGMT methylation status is the most commonly used biomarker in GBM and, studies suggest, may be predictive of the likelihood of patients with GBM to respond to alkylating chemotherapy such as temozolomide.
Patients with MGMT-unmethylated GBM are generally known to have a worse prognosis than patients with MGMT-methylated GBM.

At Bristol-Myers Squibb, patients are at the center of everything we do. The focus of our research is to increase quality, long-term survival for patients and make cure a possibility.