Strike three: Bristol-Myers’ third I/O shot at glioblastoma misses as Opdivo flops yet again on key endpoint
Glioblastoma continues to defy about everything thrown at it.
Bristol-Myers Squibb put out word Thursday morning that its third Phase III assault on brain cancer using its star PD-1 Opdivo failed the first endpoint, with no significant improvement in progression-free survival for patients who face grim odds.
CheckMate-548 appears headed for a complete collapse, though overall survival is still being studied. Researchers had tried to see if the checkpoint therapy could outdo the standard of care by adding it to the standard — temozolomide and radiation therapy.
They already tried — and failed — earlier this year with CheckMate-498, a Phase III that combined Opdivo and radiation against temozolomide. That trial failed the mark on OS in May.
Two years ago the company was forced to concede defeat on Checkmate-143, the first use of a PD-1 against glioblastoma.
Bristol-Myers has had a string of setbacks in the clinic with Opdivo, though the pharma giant still enjoys blockbuster revenue even as Merck’s Keytruda continues its clinical blitz that put them on top of the market.
In this case, though, the Bristol-Myers team joins a long list of failures in fighting brain cancer, which remains one of the toughest targets in oncology. AbbVie had its own bitter setback to report in May when their antibody-drug conjugate depatuxizumab mafodotin (or depatux-m; previously known as ABT-414) also failed in improving survival times for brain cancer victims.
Several years ago AbbVie showed up at ASCO with ABT-414 and Rova-T to tout their potential. Rova-T failed completely for the R&D team, forcing a complete write-off of a drug they bought for $5.8 billion upfront.
A complete failure here won’t extinguish all hope that a PD-1 could yet play a role in glioblastoma. Robert Prins at the UCLA Jonsson Comprehensive Cancer Center reported evidence earlier this year from a tiny exploratory trial that a checkpoint may help patients when used ahead of surgery. But it’s a long shot.
One of the few remaining Phase III studies for glioblastoma likely to read out soon belongs to Tocagen $TOCA which is making the difficult assault with Toca 511/FC. Researchers announced several months ago that they would continue to the final readout, dashing any hopes for an early success. There isn’t much confidence in this drug, though, with the stock falling from a high north of $15 last fall to just above $3 a share this morning. The market cap is holding at a micro-level $72 million.
These failures won’t encourage others to make a try.