Dive Brief:
- Data unveiled Monday from a Phase 3 study found patients with high levels of a biomarker appeared to derive greater benefit from Bristol-Myers Squibb's Opdivo, particularly when paired with the the pharma's other immunotherapy Yervoy.
- Facing an uphill battle to challenge rival Merck & Co. in advanced lung cancer, Bristol-Myers is betting continued segmentation of patient populations will open an opportunity for its immunotherapy Opdivo to earn a share of the first-line market. Key to that strategy is the company's focus on a biomarker known as tumor mutation burden (TMB), which functions as a count of the number of mutations present in a patient's tumor.
- "Patients populations will continue to segment. You will continue to see the evolution of biomarkers," said Bristol-Myers' chief scientific officer Thomas Lynch at an investor event Monday held during the annual meeting of the American Society of Clinical Oncology.
Dive Insight:
This year's ASCO conference further solidified the position of Merck's Keytruda (pembrolizumab) as the current immunotherapy of choice for initial treatment of metastatic non-small cell lung cancer.
Researchers unveiled results from two more positive studies of Keytruda, showing the drug helped extend survival for a broader range of patients when used as monotherapy or in combination with chemotherapy. While oncologists still debated which regimen to give patients who express lower levels of a biomarker called PD-L1, Keytruda now has data supporting use in most people with NSCLC.
Keytruda's success ups the challenge for competing companies like Bristol-Myers and Roche.
For Bristol-Myers, a study called CheckMate-227 is the company's primary means of demonstrating Opdivo (nivolumab)'s relevance in first-line lung cancer. Back in April, the pharma read out results which showed a pairing of Opdivo and Yervoy (ipilimumab) cut the risk of disease worsening or death by 42% versus standard chemotherapy among patients with a TMB score of greater than 10 mutations per megabase.
According to new data from a different subset of that study, combining Opdivo with chemotherapy also improved median progression-free survival in patients who were considered PD-L1 non-expressors by about one month.
That result, which was descriptive and not tested as a primary endpoint, didn't much impress.
"This is a relatively pedestrian result, I think, for this patient population," said Thomas Stinchcombe, professor of medicine at the Duke Cancer Institute, in remarks discussing the Bristol-Myers data Monday.
Exploratory data presented by Bristol-Myers, however, appears to bolster the pharma's argument that TMB will prove a useful measure of which patients can benefit from immunotherapy.
Among 129 patients with high TMB scores, 45% treated with Opdivo plus Yervoy, and 27% treated with Opdivo plus chemo had not experienced disease progression at 12 months. For those given chemo alone, the one-year progression-free survival rate was only 8%.
If TMB is more widely adopted as a biomarker in clinical practice, Bristol-Myers could argue its combination should play a role in the initial treatment of NSCLC.
"For patients who have no PD-L1 but also have a high tumor mutation burden, I think there is certainly rationale to nivolumab plus ipilimumab without additional chemotherapy," said Leena Gandhi, associate professor of medicine at the New York University School of Medicine, in a plenary session at ASCO Sunday before the new CheckMate-227 data was released.
(Gandhi, who served as principal investigator of Merck's Keynote-189 study testing Keytruda together with chemotherapy, will soon be joining Eli Lilly to lead immuno-oncology medical development.)
Analysts, however, see much of the market going Merck's way. Investment firm Cowen forecasts Keytruda will hold about 50% of the U.S. market by 2019 versus only 13% for Bristol-Myers.
Roche, which is pinning its hopes on a four-drug combination with its PD-L1 inhibitor Tecentriq, is set to claim 31%, according to Cowen.
CheckMate-227 will continue to test Opdivo plus Yervoy's impact on overall survival in patients who express PD-L1.