LAG-3/PD-1 Inhibitor Therapy in Unresectable or Metastatic Melanoma: The RELATIVITY-047 Trial


Sajeve Thomas, MD, reflects on the RELATIVITY-047 trial combining relatlimab, a LAG-3 inhibitor, with nivolumab, a PD-1 inhibitor, in the first-line setting of unresectable or metastatic melanoma.


Sajeve S. Thomas, MD: Ultimately these are 2 distinct inhibitory checkpoints, and if you can target both LAG-3 and PD-1, you can get a synergistic response and a better response of trying to turn on these T-cells and shrink tumors, and that’s essentially what the LAG-3 is doing. It is another distinct inhibitory checkpoint. The rationale for¼this combination is to get better responses, but hopefully without seeing as many adverse effects as we’ve seen with other combinations. The RELATIVITY-047 trial (NCT03470922) was a randomized phase 3 study, a¼global study randomizing patients with metastatic melanoma. About 700 patients received nivolumab and relatlimab, versus nivolumab alone. These were patients with unresected melanoma stage IV disease. If you had autoimmune [disease], you were excluded. If you required steroids for other medical issues, you were excluded. The primary end point was progression-free survival. The secondary end points were overall survival and response rate.

In the clinical trial, the primary end point was progression-free survival. For patients who had nivolumab, the median progression-free survival was roughly 4.6 months. If you got nivo and rela, the median progression-free survival was 10.1 months, so a distinct, significant improvement in progression-free survival. Regardless of whether you’re BRAF mutated or wild type, the progression-free survival with nivo and rela was approximately the same amount, at 10 months.

If you look at ipilimumab/nivolumab, it was roughly 16 to 17 months in terms of median progression-free survival. If you looked at LAG-3 status, because they did look at PD-1 and LAG-3 status, if you were more than 1% than the median progression-free survival, it was roughly about 12 months. If you were less than 1%, it was median progression-free survival of about 4 months. If you look at overall survival, there was descriptively a change in better overall survival for those who got nivo and rela, but this was not a significant difference. So, hopefully, there are more follow-ups to see if there’s some significant difference in overall survival. In terms of response rate, nivo had a response rate of roughly 33%, and nivo and rela was about 43%, so about 10% improvement in response rate with the combination of nivo and rela. When we talk about safety issues, compared with the ipi/nivo combination, which has grade 3/grade 4 events of 50%, 55%, nivo and rela was roughly about 18% to 20% in terms of grade 3/grade 4 adverse events.

Transcript edited for clarity.

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