Opdivo Fails to Demonstrate Survival Benefit in Phase 3 Brain Cancer Trial

Opdivo Fails to Demonstrate Survival Benefit in Phase 3 Brain Cancer Trial

Patients with glioblastoma multiforme, a type of brain cancer, who recurred following radiation therapy and Temodal (temozolomide), did not survive longer when treated with the PD-1 inhibitor Opdivo (nivolumab) compared to standard-of-care treatment with Avastin (bevacizumab).

The findings mean that the randomized CheckMate -143 Phase 3 trial (NCT02017717) has failed to meet its primary objective.

“[Glioblastoma multiforme] is a historically difficult disease to treat and conventional treatment options have demonstrated limited responses,” Fouad Namouni, MD, head of Oncology Development and head of Medical at Bristol-Myers Squibb, said in a news release. “We remain steadfast in our pursuit of treatments for diseases with the highest unmet need and continue our work to determine how our immuno-oncology agents can potentially improve outcomes for these patients.”

The CheckMate -143 study was designed to evaluate the safety and effectiveness of the PD-1 inhibitor Opdivo and Opdivo plus the CTLA-4 inhibitor Yervoy (ipilimumab) in patients with recurrent glioblastoma multiforme. Both drugs are immune checkpoint inhibitors designed to harness the body’s immune system and launch anti-tumor immune responses.

The study was originally a Phase 2 trial, but findings presented at the 2016 ASCO Annual Meeting showed encouraging signs of activity in the group of patients receiving Opdivo monotherapy; 40% of patients were still alive one year after beginning treatment, with only mild adverse events reported.

Based on the findings, the company opened a Phase 3 cohort within CheckMate -143 designed to compare Opdivo monotherapy (3 mg per kilogram intravenously every two weeks until disease progression) with Avastin, administered at 10 mg per kilogram every two weeks. Avastin is currently the standard of care for patients with recurrent glioblastoma.

The Phase 3 cohort enrolled 440 participants with stage 4 recurrent glioblastoma. Its primary outcome measure was overall survival, and secondary outcomes included overall survival rate, progression-free survival, and objective response rate.

Bristol-Myers Squibb has now announced that the trial did not reach its primary endpoint, and that further data from the trial will be presented May 7 at the World Federation of Neuro-Oncology Societies 2017 Meeting in Zurich, Switzerland.

BMS is currently conducting two additional trials, CheckMate -498 (NCT02617589) and CheckMate -548 (NCT02667587), in newly diagnosed glioblastoma patients. The trials, which are moving forward as planned, are evaluating the combination of Opdivo with radiation therapy, with or without Temodal.