- Bristol-Myers Squibb Co.'s flagship immunotherapy Opdivo missed a key goal in a Phase 3 study testing the drug in combination with Yervoy for a common type of kidney cancer, hindering the drugmaker's plans to expand its immuno-oncology franchise.
- Opdivo plus Yervoy failed to clearly improve progression-free survival (PFS) over Pfizer's Sutent as a first-line treatment for advanced renal cell carcinoma, Bristol-Myers disclosed in a Tuesday update on its Checkmate-214 study.
- While the two-drug pairing did hit another primary endpoint comparing objective response rates, the lack of a statistically significant PFS benefit hurts Bristol-Myers' chances of securing U.S. approval for the new indication on this data alone.
Opdivo (nivolumab)'s mixed results in Checkmate-214 follow several high-profile setbacks for other checkpoint inhibitors in the immuno-oncology field.
Most recently, AstraZeneca plc lost nearly $14 billion in market value after its PD-L1 inhibitor Imfinzi (durvalumab) didn't hit its PFS objective in a closely watched lung cancer study. That failure, which was seen as a chance for the British drugmaker to catch up with immuno-oncology leaders, echoed Bristol-Myers own setback with Opdivo in first-line lung cancer a year earlier.
Other studies aiming to confirm the benefit of Roche AG's Tecentriq (atezolizumab) and Merck & Co.'s Keytruda (pembrolizumab) in, respectively, bladder cancer and carcinoma of the head and neck have also fallen short in recent months.
Such misses have shaded what has otherwise been a story of rapid clinical advances and commercial success for immuno-oncology. Given that drugmakers have rushed in to develop these medicines and combination therapies across hundreds of clinical studies, though, it's inevitable that the field will see both victories and setbacks as it matures.
Yet the trial failures also reflect the degree to which the science behind these new drugs still is not completely understood. One remaining question, for example, is whether progression-free survival is a good predictor the drug's ability to extend overall survival (OS).
In the earlier Checkmate-025 study, which supported approval of Opdivo as a second-line treatment for renal cell carcinoma (RCC), Opdivo improved OS by 5.4 months even though the difference in PFS between the immunotherapy and its comparator was not statistically significant.
"The results of a comparison of progression-free survival between the nivolumab group and the everolimus group suggest that progression-free survival was not a surrogate for overall survival in this study," the trial investigators wrote in The New England Journal of Medicine.
For Bristol-Myers, the hope is that Checkmate-214 in first-line RCC will follow a similar pattern. The drugmaker will continue the study to allow the OS data to mature. OS, PFS and objective response rate are each a co-primary endpoint.
Checkmate-214 was powered more heavily to show an OS benefit, raising the difficulty of hitting statistical significance on the PFS measure, Cowen analyst Steve Scala wrote in an August 16 note.
The Opdivo and Yervoy combination did lead to a higher numerical median PFS at 11.56 months versus 8.38 months in the Sutent arm, giving some optimism for a possible hit on OS.
But data on OS won't be available until the latter half of 2019, potentially delaying Bristol-Myers' ability to win a label expansion into first-line RCC if the Food and Drug Administration doesn't see enough evidence for approval based on Checkmate-214.
Shares in the drugmaker fell by a little over 1% in Wednesday morning trading.
Opdivo currently is the only checkpoint inhibitor approved in RCC, but others such as Roche's Tecentriq are being tested in the indication as well. With Merck cementing its lead in the more lucrative lung cancer market, indications like RCC will be increasingly important for Bristol-Myers as it seeks to grow Opdivo's revenue further.