- Bristol-Myers Squibb Co. said Thursday a study testing its star immunotherapy Opdivo together with Yervoy will be stopped early after an interim look at the data showed the combination improved overall survival in patients with a common type of kidney cancer.
- The positive results flip the script on the combo's prospects, which had appeared diminished in August when the drugmaker revealed the immuno-oncology pairing failed to clearly improve progression-free survival (PFS).
- Perhaps more significantly for the field, Opdivo and Yervoy's success on overall survival offers another piece of evidence suggesting PFS as a clinical endpoint may not fully capture the benefit of immunotherapy.
Overall survival results from the CHECKMATE-214 study hadn't been expected to read out until the second half of 2019. So Thursday's announcement an independent data monitoring committee recommended halting the trial early due to efficacy was a welcome boost from Bristol-Myers.
Opdivo (nivolumab) is currently the only checkpoint inhibitor approved to treat advanced renal cell carcinoma (RCC), having won approval as a second-line treatment in November 2015. CHECKMATE-214 is designed to expand that label to include previously untreated patients by pairing Opdivo with Bristol-Myers other immunotherapy Yervoy (ipilimumab).
The combo improved overall survival versus Pfizer's Sutent (sunitinib) in both the primary study population of intermediate- and poor-risk patients as well as in all randomized patients in the trial.
Bristol-Myers said it would share results of the study with regulators, indicative the company will likely file for approval.
"We expect Bristol to file for this indication shortly; approval would make Opdivo [plus] Yervoy the first approved [immuno-oncoloy] combination in the first line renal setting," wrote Cowen & Co. analyst Steve Scala in a Sept. 7 note.
Shares in the company closed 5% higher Thursday on the news.
Opdivo and Yervoy's failure to show a statistically significant benefit on PFS, only to later improve overall survival, mirrors the performance of Opdivo monotherapy in initial studies in second-line RCC. In the CHECKMATE-025, treatment with Opdivo led to a 5.4-month improvement in survival despite not demonstrating superior PFS.
Such a pattern raises hopes that AstraZeneca's rival Imfinzi (durvalumab) may also overcome a damaging miss on PFS to eventually show a survival benefit down the road. The drug created reverberations around the industry when it reported the negative result from its MYSTIC study in non-small cell lung cancer.
Scala views the overall survival data in CHECKMATE-214 as a positive sign for Bristol-Myers' CHECKMATE-227 study in first-line non-small cell lung cancer (NSCLC). That trial also pairs Opdivo with Yervoy and could put Bristol-Myers in a more competitive position in the all-important lung cancer market, if successful.
Lung cancer update
On Friday, Bristol-Myers Squibb also released follow-up data which showed a three-year survival benefit to Opdivo versus the chemotherapy docetaxel in two types of NSCLC. The results help confirm Opdivo's efficacy over a longer time horizon, setting the bar for other checkpoint inhibitors in the second-line market.
In one, called CHECKMATE-017, 16% of patients with squamous NSCLC treated with Opdivo were alive after three years versus only 6% of those receiving docetaxel — a 38% reduction in relative risk. The second, testing patients with non-squamous NSCLC, showed a lower 27% risk reduction.
Interestingly, among patients treated with Opdivo in that second study, 26% with PD-L1 expression higher than 1% were alive after three years compared to only 11% with PD-L1 expression less than 1%. PD-L1 expression measures have a rough guide of which patients are most likely to respond to checkpoint inhibitors, although the correlations are not always as neat as drugmakers would like.
Editor's note: This article has been updated to include updated results from two lung cancer studies of Opdivo versus docetaxel.