Opdivo/Yervoy combo for melanoma fails in key patient population
Bristol-Myers Squibb’s efforts to expand their checkpoint inhibitor combination have run into another recalcitrant cancer.
The NJ-based pharma announced that a combination of Yervoy and Opdivo didn’t beat out Opdivo alone in patients with resected high-risk melanoma who had very low levels of PD-L1. The drug combo couldn’t improve recurrence-free survival in these post-surgery patients.
The results mean that adding a CTLA4 inhibitor to a PD-1 inhibitor didn’t help the patients who lacked PD-L1 ligands. Bristol-Myers is continuing the study, Checkmate-915, to see if the combo helps the larger, all-comer pool.
Although the trial will go on, the failure of PD-1 negative patients is significant, Checkpoint combination therapies were explored in part on the promise of helping patients who didn’t test positive for PD-L1 — a population that represents about 60% of melanoma patients, per some estimates.
The New England Journal of Medicine study that burnished the first FDA approved checkpoint combination therapy in 2015 — a combination of Opdivo and Yervoy in unresectable melanoma — showed that compared with Opdivo alone, the combo more than doubled progression-free survival in PD-L1 negative patients, from 5.3 months to 11.2 months. Subsequent data showed it also brought slight improvements in overall survival.
Although Bristol-Myers had the early lead on checkpoint therapies, they’ve been losing out to Merck and their PD-1, Keytruda — a drug some analysts expect to top $20 billion by 2024. That race and their lagging place helped trigger the Celgene acquisition that closes today.
Combination checkpoints therapy has been a mixed but mostly successful strategy for Bristol-Myers Squibb. Last year, the combo failed a Phase III for small cell lung cancer. Three, though have been approved and the company has pushed hard for more, most recently touting the results of a Phase III trial on non-small cell lung cancer and winning breakthrough status and speedy review for liver cancer.
The idea of combining these two checkpoint inhibitors into a single therapy is to better target the tumor and overcome resistance by hitting it in different ways. But critics note they have rarely led to huge increases in survival over single-agent therapies and that together, the two can lead to high toxicities.