As a result, the company has decided to unblind the treatment assignments of patients in the trial.
Bristol Myers’ CEO Giovanni Caforio pictured above. Photo by Win McNamee/Getty Images
Bristol Myers Squibb reported that the independent Data Monitoring Committee (DMC) had reviewed its CheckMate -548 Phase III trial of Opdivo (nivolumab) plus current standard of care in patients with newly diagnosed glioblastoma multiforme (GBM) with 06-methylguanine-DNA methyltransferase (MGMT) promoter methylation following surgical resection of the tumor. Unfortunately, the committee’s assessment indicated the trial would not meet its primary endpoint of overall survival (OS) in patients with no baseline corticosteroid use or in the overall randomized population. There were no safety concerns.
As a result, the company has decided to unblind the treatment assignments of patients in the trial. Patients will be provided information on their options for treatment going forward, and patients that were showing benefit from Opdivo can continue treatment if they and their physician agree.
Opdivo is a checkpoint inhibitor against PD-1. Glioblastoma (GBM) is the most common and most aggressive form of malignant tumor of the central nervous system. It affects about 10 in 10,000 people. Standard treatment for people recently diagnosed with GBM is surgery followed by radiation and chemotherapy, but the options for treatment are limited. The five-year survival rate is less than 5%.
CheckMate -548 evaluated Opdivo in addition to standard of care, which is temozolomide and radiation therapy compared to placebo plus standard of care. The primary endpoints are progression-free survival (PFS) per blinded independent central review (BICR) in all randomized patients and overall survival (OS) in patients with no corticosteroid use at baseline as well as in all randomized patients. The secondary endpoints are PFS and OS rate at 12 and 24 months as evaluated by investigator. In September 2019, Bristol Myers Squibb announced the trial did not meet its primary endpoint of PFS in all randomized patients.
“Glioblastoma is an aggressive cancer with a very poor prognosis that has seen limited new treatment options over the last 15 years,” said Michael Mandola, Oncology Development Program Lead, Bristol Myers Squibb. “We are disappointed that CheckMate -548 did not meet its desired outcome despite limiting enrollment to patients with MGMT promoter methylation, which we believed may have led to improved survival. We are grateful to the patients, caregivers and investigators for participating in this trial and will continue to work with the oncology community in the pursuit of effective therapies for patients with this difficult disease.”
Earlier this month, the company announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) recommended approval of Inrebic (fedratinib) for disease-related splenomegaly or symptoms in adults with primary myelofibrosis, post-polycythemia vera myelofibrosis or post-essential thrombocythemia myelofibrosis, who are JAK inhibitor naïve or have been treated with ruxolitinib. The European Commission will then review the recommendation. If Inrebic is approved, it will be the first, once-daily oral therapy to reduce spleen size and symptom burden for patients with myelofibrosis where ruxolitinib treatment has failed or patients who have not received JAK inhibitor treatment.
The positive opinion was based on data from the JAKARTA and JAKARTA2 studies.
Inrebic is an oral kinase inhibitor with activity against wildtype and mutationally activated JANUS 2 and FMS-like tyrosine kinase 3 (FLT3). The drug is a JAK2-selective inhibitor with higher potency for JAK2 over JAK1, JAK3 and TYK2.
