FDA Approval: Nivolumab (Opdivo) for Melanoma

The date, from the FDA's own file

The openFDA Drugs@FDA record for nivolumab is BLA 125554, sponsored by Bristol Myers Squibb. The original approval is dated December 22, 2014. It was a priority review of a new molecular entity.

The drug is sold as Opdivo. Melanoma was its first approved use.

What a checkpoint inhibitor does

T cells are the immune system's killers. They carry a switch called PD-1 on their surface. When PD-1 meets its partner proteins, PD-L1 or PD-L2, the T cell stops multiplying and stops releasing the signals that summon help.

That switch exists to stop the immune system attacking healthy tissue. Some tumors exploit it. The label says upregulation of those partner proteins happens in some cancers, and signaling down that path can shut off the immune surveillance that would otherwise find the tumor.

Nivolumab is an antibody that binds PD-1 and blocks that handshake. It does not attack the cancer. It removes the brake and lets T cells do it.

Ipilimumab, often given with it, releases a different brake called CTLA-4. The label states that blocking both together produces a stronger T-cell response than either alone. Our page on immunotherapy covers the wider family.

The trial behind the melanoma approval

NCI summarized CheckMate-066. It enrolled 418 people with untreated metastatic melanoma whose tumors carried no BRAF mutation, and randomly assigned them to nivolumab or to dacarbazine, the chemotherapy drug then in common use.

At publication, median overall survival had not been reached in the nivolumab group. It was 10.8 months with dacarbazine. One-year survival was 72.9% against 42.1%. Median progression-free survival was 5.1 months against 2.2 months, and 40.0% of people on nivolumab had their tumors shrink, against 13.9%.

Severe side effects were less common with nivolumab: 11.7% had grade 3 or 4 events, against 17.6% with chemotherapy.

One finding surprised people. Within the nivolumab group, survival was no different between those whose tumors tested positive for PD-L1 and those who tested negative. The obvious biomarker did not sort responders from non-responders.

What the label covers now

The indication has grown well past 2014. The current label lists nivolumab for adults and children aged 12 and over with melanoma that cannot be removed by surgery or has spread, either alone or with ipilimumab. It also covers adjuvant treatment — given after surgery to lower the chance of return — for completely removed stage IIB, IIC, III, or IV melanoma.

NCI reported the combination approval separately. On September 30, 2015, the FDA granted accelerated approval to nivolumab plus ipilimumab for melanoma without a BRAF V600 mutation. Among 109 people with that tumor type, 60% responded to the combination against 11% on ipilimumab with placebo, and median progression-free survival was 8.9 months against 4.7 months.

That gain came at a cost. Serious adverse reactions occurred in 62% of people on the combination, against 39% on ipilimumab alone.

The side effects that define this drug class

Releasing an immune brake means the immune system can turn on healthy organs. The label puts immune-mediated reactions first among its warnings, notes they may be severe or fatal, and says they can occur in any organ.

It names the main ones: pneumonitis in the lungs, colitis in the bowel, hepatitis in the liver, endocrine problems including the thyroid, skin reactions, and nephritis in the kidneys.

The label's instruction is monitoring, not avoidance. Liver enzymes, creatinine, and thyroid function are checked at the start and periodically during treatment. Treatment is paused or stopped depending on how severe the reaction is.

Other warnings cover infusion reactions, serious complications in people who have a donor stem cell transplant before or after PD-1 blockade, and harm to a fetus.

The wider picture

Melanoma is common but usually caught early. The American Cancer Society projects 112,000 US diagnoses and 8,510 deaths for 2026, while NCI's own SEER records show 94.7% five-year relative survival across all stages for 2016 through 2022 diagnoses.

That average hides the split. Survival is 100.0% for localized disease, 76.0% for regional, and 34.0% once it is distant. Only about 5% of melanomas are distant at diagnosis, and that small group is where drugs like nivolumab do their work. Our page on melanoma stages explains how extent is described.

These are group figures from past years. They do not describe any one person.

When to get checked

Two different questions sit under this heading.

For anyone on a PD-1 blocking drug, the label's warning list translates into symptoms worth reporting to the treatment team the day they appear, not at the next appointment:

• A new or worsening cough, or breathlessness on ordinary effort
• Diarrhea, more stools than usual, or blood or mucus in them
• Yellowing of the skin or eyes, dark urine, or pain under the right ribs
• Deep tiredness, feeling cold all the time, or unexplained weight change
• A rash that spreads, blisters, or peels
• Passing much less urine than usual

These are the organ systems the label names: lungs, bowel, liver, hormone glands, skin, and kidneys. Blood tests for liver enzymes, creatinine, and thyroid function are checked before treatment and at intervals during it.

For anyone else, the question is spotting melanoma early. NCI lists a mole that changes in size, shape, or color, has ragged edges, shows more than one color, is asymmetrical, itches, oozes, bleeds, or opens up, or has new small moles growing beside it. A diameter over about 6 mm is a further prompt.

What this does not mean

• An approval sets out who is eligible in general terms. Whether it fits one person is a clinical judgment.
• CheckMate-066 compared nivolumab with dacarbazine, which is no longer the standard first choice. It does not rank nivolumab against today's other options.
• A negative PD-L1 test did not predict failure in this trial. Biomarker results are read differently in different cancers.
• Labels change. The version described here is the one on DailyMed at the source-check date.

Sources

• openFDA Drugs@FDA API record for OPDIVO (BLA 125554) — https://api.fda.gov/drug/drugsfda.json?search=openfda.brand_name:%22OPDIVO%22&limit=1
• NCI, Nivolumab Improves Overall Survival in Patients with Metastatic Melanoma without a BRAF Mutation — https://www.cancer.gov/types/skin/research/nivolumab
• NCI Cancer Currents, FDA Approves Nivolumab for Some Melanomas and Lung Cancers — https://www.cancer.gov/news-events/cancer-currents-blog/2015/nivolumab-expanded
• DailyMed, OPDIVO (nivolumab) prescribing information — https://dailymed.nlm.nih.gov/dailymed/services/v2/spls/f570b9c4-6846-4de2-abfa-4d0a4ae4e394.xml
• NCI PDQ, Melanoma Treatment (Patient Version) — https://www.cancer.gov/types/skin/patient/melanoma-treatment-pdq
• SEER Cancer Stat Facts, Melanoma of the Skin — https://seer.cancer.gov/statfacts/html/melan.html

How this article was prepared

An AI-assisted editorial system helped prepare this page. No named medical reviewer has reviewed it unless one is listed.

The National Cancer Information Foundation publishes Cancer Explained. This page is for learning. It is not medical advice and does not suggest a test or treatment.

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