In a First, FDA Approves Immunotherapy Combination for Advanced Melanoma

Today the FDA announced accelerated approval of a combination of immunotherapy drugs for the frontline treatment of advanced melanoma. The drugs, ipilimumab (Yervoy®) and nivolumab (Opdivo®), made by Bristol-Myers Squibb (BMS), are two immune checkpoint inhibitors that “release the brakes” on the immune system, allowing it to mount a stronger and more effective attack against cancer. The FDA based its approval on results from a clinical trial showing that patients who received the combination had better responses than those who received ipilimumab alone.

Melanoma experts applauded the FDA’s decision. “Today’s approval represents a step forward for the melanoma community, providing hope for patients with metastatic melanoma,” said Jedd D. Wolchok, MD, PhD, a medical oncologist at the Ludwig Center at Memorial Sloan Kettering Cancer Center and director of CRI’s clinical program, in a press release.

Today’s much-anticipated approval caps a headline-grabbing journey that began more than 2 years ago, when the cancer world first heard about promising clinical results obtained with the ipi + nivo combination. At the annual meeting of the American Society of Clinical Oncology (ASCO) in June of 2013, Wolchok presented results of a phase I trial showing that patients who received the combination experienced “rapid and deep regressions” of their tumors. The results captivated both doctors and patients alike, and have since generated sustained enthusiasm for the combination, which researchers have tested in multiple clinical trials, including a large and ongoing phase III trial.

Today’s accelerated approval was based on the results of a phase II trial, called CheckMate-069, which enrolled patients with previously untreated advanced melanoma and gave them either the combination of ipi + nivo or ipi alone. Among 109 patients, the combination had a response rate of 60% compared to 11% for ipi alone, with 17% of the combo-treated patients experiencing a complete response compared to 0% for those who received ipi alone. The median progression-free survival for the combination group was 8.9 months versus 4.7 months for ipi alone. Today’s approval applies only to patients without a BRAF V600 mutation. Continued approval for this indication is contingent on additional data showing an improved overall survival benefit to patients.

Checkpoint inhibitors like ipilimumab and nivolumab represent some of the most promising immunotherapy drugs in use today. These drugs target proteins on immune cells that act like brakes, or checkpoints. By releasing these immune brakes, the drugs allow a stronger and more powerful immune attack against cancer. Ipilimumab blocks a braking molecule on immune cells called CTLA-4, while nivolumab blocks another called PD-1. Ipilimumab was approved by the FDA in 2011 as frontline treatment of advanced melanoma; nivolumab was approved in 2014 for melanoma that is no longer responding to ipilimumab or to other drugs.

Researchers have high hopes for combination immunotherapy approaches to treat cancer. Because the immune system has a system of multiple checks and balances—both gas pedals and brakes—drugs that target these levers in combination hold the promise of powerful complementary and even synergistic effects. Researchers are also exploring a similar combination of CTLA-4-blocking and PD-1-blocking drugs in other cancer types, including lung cancer. CRI’s Clinical Accelerator is undertaking one such study, a phase I trial of the CLTA-4-blocking drug tremelimumab plus the PD-L1-blocking drug durvalumab for patients with a variety of solid tumors.

The list of patients who have benefited from the ipi + nivo immunotherapy combination is long and growing. You can read one patient’s story and watch a video here. Melanoma patients should ask their doctors about receiving the combination regimen. Any patients experiencing difficulties getting access to the drug combination should visit BMS Access Support®.

As powerful as these drugs are, not everyone responds to them, and they are not without risk of significant though usually manageable toxicities. The Cancer Research Institute is committed to funding additional basic, clinical, and translational research that will help bring effective immunotherapies to more patients with all types of cancer.