Who is this for?
This is for people with advanced (metastatic or unresectable) melanoma who are starting their first drug treatment.
Melanoma is one of the cancers that responds best to immunotherapy. This trial asked whether releasing a second, newly-discovered immune brake — on top of the usual one — could work even better.
What kind of trial is this?
RELATIVITY-047 was a global phase II–III randomized, double-blind trial — a rigorous design. It compared the fixed-dose combination of relatlimab + nivolumab against nivolumab alone, as a first treatment for advanced melanoma.
Background: a third brake to release
Immunotherapy works by taking the brakes off the immune system so it can attack cancer. For years, only two brakes could be targeted with drugs — PD-1 (blocked by nivolumab) and CTLA-4 (blocked by ipilimumab; see our kidney-cancer summary for how those two work). LAG-3 is a third brake, found on worn-out immune cells inside tumors. Relatlimab is the first drug able to release it — and RELATIVITY-047 tested whether adding it to nivolumab helps.
The trial: what was tested and how
RELATIVITY-047 enrolled 714 people with untreated advanced melanoma, randomly assigned to one of two treatments given as an infusion every 4 weeks:
- Relatlimab + nivolumab: the two immunotherapy drugs together (as a single combined infusion).
- Nivolumab alone: the standard single immunotherapy drug.
The main measure was progression-free survival — how long the cancer was held in check.
Results: what they found
Releasing the extra LAG-3 brake kept the cancer in check for longer — and, with four years of follow-up, helped people live longer as well — at the cost of somewhat more side effects than nivolumab alone.
Relatlimab + nivolumab vs nivolumab alone
The cancer was kept from growing more than twice as long — a 22% lower risk of progression or death (HR 0.78). At 4 years, 31% vs 24% were still free of progression.
With four years of follow-up, a survival benefit emerged that wasn’t yet clear at first: people lived a median of about 20 months longer (HR 0.77), and 52% vs 43% were alive at 4 years.
The combination roughly doubled serious side effects compared with nivolumab alone — but this is notably lower than the older two-drug combination (nivolumab + ipilimumab), which causes them in about half of people.
What is LAG-3?
LAG-3 (lymphocyte-activation gene 3) is a protein that appears on immune cells that have become “exhausted” inside a tumor — it acts as a brake that dampens their attack. Blocking it can re-energize those worn-out cells. Relatlimab was the first drug approved to block LAG-3, making this combination the first new class of checkpoint inhibitor in years.
How does this compare with nivolumab + ipilimumab?
Both are two-drug immunotherapy combinations that outperform a single drug. The older pairing, nivolumab + ipilimumab, is very potent but causes serious side effects in about half of people. Relatlimab + nivolumab offers a gentler middle option: stronger than nivolumab alone, with far fewer severe side effects than the ipilimumab combination. Which to choose depends on the person and their disease — a decision made with the oncology team.
The bottom line
For advanced melanoma, adding relatlimab — the first drug to release the newly-targeted LAG-3 brake — to nivolumab held the cancer in check more than twice as long as nivolumab alone (10.2 vs 4.6 months). With four years of follow-up, it also helped people live longer (median 53.3 vs 33.2 months; 52% vs 43% alive at 4 years). It brings a third class of checkpoint inhibitor into cancer care, and offers a first-line option that is stronger than a single immunotherapy but easier to tolerate than the older two-drug combination.
What this could mean for you
- A newer immunotherapy option. For advanced melanoma, relatlimab + nivolumab is a first-line choice that targets a brand-new immune target.
- A middle ground on side effects. More effective than one drug, gentler than the older two-drug combination — a useful balance for many people.
- The choice is individual. Which immunotherapy combination fits best depends on your disease and health — worth discussing with your oncologist.
Questions & comments
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