ASCO 2025 | RELATIVITY-020: dose comparison of nivolumab and relatlimab in melanoma

In a poster, I presented the results of the cohort E on RELATIVITY-020  trial. So that was the phase one/two trial exploring nivolumab combined with relatlimab in different patient populations. And in that trial, we randomized to the first-line setting. So first-line advanced melanoma, different dosing schedules of relatlimab. So nivolumab combined with relatlimab in the current standard as seen in Relativity-047 of 480 milligrams of nivolumab plus 160 milligrams of relatlimab. That’s our standard dosing versus 480 nivolumab plus 480 of relatlimab. So that was a randomized trial. It was phase two randomized in the advanced setting. What we found was a slightly higher response rate with the higher dose of relatlimab. But this did not translate into a prolonged progression-free survival or overall survival, only in a higher response rate. However, the median number of doses of drugs was lower in the higher dose relatlimab cohort in this randomized study and toxicities were slightly higher in the higher dosing of relatlimab. So the question is how are we managing toxicities, what is causing this lack of efficacy effect with the higher dose of anti-LAG-3. That’s yet to be explored. Was it possibly immunosuppression? Was it that there was not enough checkpoint inhibitor given? It’s interesting there was a higher response rate. However, this did not translate into time to event analyses, Kaplan-Meier analyses for progression-free survival or overall survival. So a lot more to be explored. My take-home message for that though is within the field of oncology, using checkpoint inhibitors and immunotherapy, we really do need to get better at reducing the risk of toxicities and dosing these drugs appropriately. It’s not by strict intervals that we do this in the real world. We know that if you watch the patient, read the patient’s immune system, look at blood tests, look at the patient, then decide whether you’ll go in with your second, third or fourth dose of immunotherapy. If a patient has a particularly active immune system, hang back. Don’t go in with cycle two, wait, wait for the T cells to settle down, follow them with regular blood tests, see them again, and then decide whether you’ll give cycle two or three. And always you can do a scan early to see if you’re getting an anti-tumor response so you’re more confident about waiting for the second or third, fourth dose of immunotherapy. I think if we make a more nuanced approach and personalize the intervals, we will see less toxicity, less immunosuppression and possibly more efficacy.

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