- Along with full-year earnings, Bristol-Myers Squibb Company announced positive topline results for its CheckMate-227 trial in the first-line non-small cell lung cancer setting — potentially a market-changing result.
- The pharma full-year revenues increased 7% to $20.8 billion, with drugs like Eliquis and Opdivo driving growth. Eliquis revenues were up 46% to $4.9 billion, while Opdivo increased 31% to $4.9 billion.
- While Bristol-Myers executives cast an optimistic tone, some analysts on an investor call were a bit more skeptical, seeking clarity beyond scant details released on the data.
Results from the ongoing Phase 3 CheckMate-227 trial showed that first-line patients with non-small cell lung cancer and expressing a biomarker called tumor mutation burden (TMB) showed "highly statistically significant" progression-free survival with a combination of Opdivo (nivolumab) and Yervoy (ipilimumab) versus chemotherapy.
The trial will continue as overall survival data matures.
After competitor AstraZeneca plc's failure in the closely watched MYSTIC trial, Bristol-Myers made significant changes to the design of CheckMate-227 to optimize results.
"First, we increased the size of Part 1a. This gave us more statistical optionality and lowered the potential for imbalances in the PD-L1 positive patients," said CSO Thomas Lynch on the Feb. 5 call with analysts.
"Second, we added a second part, Part 2, to '227. This is a study of about 750 patients who were enrolled regardless of histology and across the PD-L1 spectrum, comparing Opdivo plus chemotherapy versus chemotherapy alone. And third the change we made was to our analysis plan for Part 1, which allowed us to include TMB."
These disappointed investors at the time, but it seems the strategy paid off.
The key to these changes was that the trial no longer focused on PD-L1 expression as the key biomarker for determining patients and instead focused on the new biomarker TMB. The company noted that nearly 45% of patients assessed were considered high-TMB.
"We've known for quite some time that PD-L1 expression has been an imperfect biomarker," added Lynch. The company sees the results as game-changing and are expecting the data to change the market dynamic for first-line lung cancer.
Currently, Merck's Keytruda (pembrolizumab) monotherapy is the only PD-1/L1 inhibitor to gain approval in this patient population, considered the most lucrative of cancer indications. Yet the efficacy of Keytruda is dependent on patients having high PD-L1 expression and clinicians have been reticent to use the drug across the first-line setting. Keytruda is approved in combination with chemotherapy regardless of PD-L1 expression.
Lynch pointed out during the call that many clinicians are confused about what to do for patients that do not have high levels of PD-L1.
"We're very encouraged by today's results, which establish TMB as an important new independent biomarker for selecting patients that response to immunotherapy," said Lynch. "We believe TMB could be important more broadly."
Bristol-Myers said that it has now started testing for TMB expression across its immuno-oncology clinical program. Over the next year and half, the big pharma expects results across multiple different types, including head and neck, small cell lung cancer, gastric and renal cell carcinoma.
Some analysts on an investor called sought more information. They want data on how the combo performed in moderate TMB expressers compared with high-TMB expressing patients, which could determine the size of the potential market.
Bristol-Myers expects to release full data from CheckMate-227 at an upcoming medical meeting.