Bristol-Myers Squibb’s closely watched study dubbed Checkmate-227 hit early, with researchers touting a success for their combination of Opdivo and Yervoy in treating frontline non-small cell lung cancer cases.
In a statement the company $BMY says that researchers tracked a “highly” significant progression-free survival rate for patients with a high tumor mutation burden (TMB), regardless of PD-L1 expression. Their combination was compared with chemo in the study, which is still tracking for overall survival results.
That’s a significant group, analysts note, pointing to Bristol-Myers’ projection that the TMB crowd accounts for 45% of all frontline patients. Bristol-Myers redesigned the study to go after the biomarker after stumbling on a pivotal trial that involved a patient population that was not so narrowly defined. All the developers are shifting to a biomarker focus as they duke it out for specific slices of a mega blockbuster-sized market.
Skeptics, though, began to retaliate early, and after a sharp jump early in the day, shares are trading down 3% as critics wonder if Bristol-Myers can follow through with convincing data. We asked lung cancer expert Jack West for his take, which you can see here, questioning the way the biomarker was handled and noting that practitioners will need to see more before changing the way they treat patients.
Hustling along in search of positive data, Bristol-Myers essentially integrated two parallel studies involving more than 1,700 patients. And R&D chief Tom Lynch told analysts this morning that there’s more work to be done on TMB-defined studies, with upcoming data readouts on gastric, lung and head and neck cancers.
Some analysts had been wondering if Bristol-Myers might just call a success today, with its Q4 report coming up. Past mishaps for Opdivo in the all-important NSCLC group cost it big time as Merck surged ahead with a combination of Keytruda and chemo.
Just a few days ago Seamus Fernandez at Leerink noted:
While success at the OS interim represents a very high bar, this would be a hugely positive surprise. We believe a win here would suggest that Opdivo + Yervoy could have a critically important place in the treatment of NSCLC.
Bristol-Myers CEO Giovanni Caforio called it a “breakthrough in cancer research and a meaningful step forward in determining which first-line lung cancer patients may benefit most from the combination of Opdivo and Yervoy.”
“TMB has emerged as an important biomarker for the activity of immunotherapy. For the first time, this Phase 3 study shows superior PFS with first-line combination immunotherapy in a predefined population of NSCLC patients with high TMB,” said Matthew Hellmann, study investigator and medical oncologist at Memorial Sloan Kettering Cancer Center. “CheckMate-227 showed that TMB is an important, independent predictive biomarker that can identify a population of first-line NSCLC patients who may benefit from the nivolumab plus ipilimumab combination.”
Not everyone was impressed by the top-line results, though.
Although this was a positive trial, TMB is such a nonspecific (and expensive) biomarker I still see this a hypothesis generating and we need to use what we learn from this to find a truly specific marker for IO benefit. #LCSM https://t.co/B6Q8PhemTQ
— Nathan A. Pennell MD, PhD (@n8pennell) February 5, 2018
The win here is also a plus for Foundation Medicine $FMI, which provided the test used to pick patients with a high TMB.
AstraZeneca — which earlier recorded a major fail for its combination of its checkpoint drug Imfinzi and tremelimumab, another PD-1/L1 checkpoint combined with an experimental CTLA-4 drug — failed the first step on PFS with their combo. The OS data is due out later in the year.
The implications for Bristol-Myers are considerable. An early leader in the field, the R&D team on Opdivo have been working feverishly to get their PD-1 back on track following a key miss in lung cancer. But a success here on PD-1/CTLA-4 will likely trigger fresh chatter of a possible takeover bid by Pfizer, which has never lost its appetite for a mega-merger. On the other hand, such a takeover would also threaten one of the most innovative of the big biopharma companies.
Opdivo earned close to $5 billion last year, a 31% increase over 2016, making this their biggest selling franchise drug. Eliquis is now their number two therapy, highlighting Opdivo’s oversized role in the company’s future.
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