A LAG-3, Opdivo combo from Bristol-Myers offers a proof-of-concept glimpse of limited success
CHICAGO — Now that the first wave of PD-(L)1 drugs has splashed out and is getting established in the cancer market, one of the next steps down the pipeline involves matching up checkpoint inhibitors in new combos as the leaders in the field pursue a fast and furious R&D strategy to market expansion. To that end, Bristol-Myers Squibb $BMY turned up at ASCO with some intriguing proof-of-concept data that marries their drug Opdivo with a LAG-3 drug, offering an early glimpse on how it could work for a particular category of patient.
Their combo, BMS-986016, achieved a 12.5% objective response rate among 55 melanoma patients who had already been on a PD-(L)1 therapy. More importantly, there was significant split in responses among patients based on LAG-3 expression, with 20% of the patients with at least 1% of tumor-associated immune cells within the tumor margin achieving an ORR compared to 7.1% with less than 1%.
Jefferies’ Biren Amin concluded that the data were underwhelming, but an adjustment around LAG-3 expression could enhance its future.
Opdivo was the first of the PD-(L)1s to dominate the market, but after Bristol-Myers’ trial work derailed on a misstep in lung cancer, the big biotech has doubled down on oncology, shaking up its R&D group and tackling a steadily widening number of studies. This is one step back in the right direction.
“As a potentially synergistic immune pathway to PD-1/PD-L1, LAG-3 has emerged as an immune checkpoint receptor that regulates T cell function and whose inhibition may increase benefits for patients,” said Paolo Ascierto of the Istituto Nazionale Tumori Fondazione Pascale of Naples, Italy. “These results indicate that BMS-986016 in combination with Opdivo may offer clinical benefit, particularly for patients whose tumors contain immune cells that express LAG-3. Further investigation is warranted to understand the impact of this combination as well as the utility of LAG-3 as an immune biomarker.”