Bristol Myers Squibb’s Opdivo and Yervoy only just won their first approval in previously untreated metastatic non-small cell lung cancer, but the pair is already making it two.
The FDA on Tuesday greenlighted the immuno-oncology duo alongside two cycles of platinum chemo for first-line patients without EGFR or ALK mutations, regardless of whether their tumors express biomarker PD-L1. The go-ahead comes just 11 days after the agency cleared Opdivo and Yervoy for use sans chemo in PD-L1-positive patients.
But while a chemo-free regimen offers its advantages—namely, helping eligible patients avoid some of chemo’s harmful side effects—industry watchers have been more focused on the chemo cocktail’s potential to spark responses early and keep them going.
With the trio, BMS hoped to deliver a "fast initial response" from chemo along with the "durable longer-term benefit to patients" Opdivo and Yervoy have already shown they can provide, Wolfe Research analyst Tim Anderson wrote in an October note to clients.
Based on data from the Checkmate 9LA trial set to be presented this weekend at the American Society of Clinical Oncology (ASCO) virtual annual meeting, that plan seems to have worked. With a minimum follow-up of 8.1 months, Opdivo, Yervoy and chemo cut patients’ risk of death by 31%—well above the 21% death risk reduction Opdivo and Yervoy posted on their own in the Checkmate-227 trial.
And those figures improved with longer follow-up. At the 12.7-month mark, the combo had pared down the death risk by 38% in in patients with PD-L1 levels below 1% and by 36% in patients with PD-L1 levels of 1% or more.
Of course, despite clearing its clinical and regulatory hurdles, BMS still has a major challenge before it, and that’s stealing share from another chemo combo: that of archrival Merck, whose Keytruda has been gobbling up global first-line market share for three years on the back of data showing it could cut patients’ death risk by 51%.
In addition to a late start, BMS may also be dealing with additional side effects from its combo’s additional drug—although industry watchers won’t know the extent until this weekend’s ASCO presentation.
“Opdivo plus Yervoy by itself shows toxicity, and adding chemotherapy into the mix will only increase this. The commercial value of CM-9LA will therefore depend on the balance between the clinical benefit and the toxicity,” Anderson wrote in October, adding, “it will only be once full results are presented” that a risk-benefit assessment “will be possible.”