Immunotherapy Approvals in 2015

Some will say that immunotherapy became a household word in 2015. That’s in large part to the significant number of FDA approvals. Checkpoint blockade—called so because they “release the brakes” on the immune system, allowing it to mount a stronger and more effective attack against cancer—was FDA approved for melanoma, lung cancer, and kidney cancer. A new type of immunotherapy—oncolytic virus therapy—got approval in October to treat melanoma. And there are now more than 20 approved antibody-based drugs, including new immunotherapies for neuroblastoma and multiple myeloma. Let’s take a look!

Checkpoint Inhibitors

• A combination of ipilimumab (Yervoy®)—an anti-CTLA-4 antibody—and nivolumab (Opdivo®)—an anti-PD-1 antibody—was FDA approved on September 30, 2015, for melanoma. Ipilimumab approved in 2011 as a monotherapy, and was the first treatment ever shown in a large, randomized phase III clinical study to improve overall survival in patients with metastatic melanoma, the deadliest form of skin cancer. Nivolumab received FDA approval on December 22, 2014, also for melanoma. The most recent approval is based on a phase II trial that showed that ipilimumab and nivolumab worked in synergy; the combination had a response rate of 60%, compared to 11% treated with just ipilimumab. What’s more, 17% of the combo-treated patients experienced a complete response, compared to 0% for those who received ipilimumab alone.

• Nivolumab (Opdivo®) had a big year on its own. It was FDA approved for squamous (March 4, 2015) and non-squamous (October 9, 2015) non-small cell lung cancer, the leading cause of cancer-related death in the U.S. and the world. With the initial approval, nivolumab became the first immunotherapy drug approved for lung cancer. It was approved, again, for renal cell carcinoma (RCC), the most common form of kidney cancer, on November 23, 2015.

• Pembrolizumab (Keytruda®), a PD-1 antibody, was approved on October 2, 2015, for patients with metastatic non-small cell lung cancer that expresses a protein called PD-L1.

Oncolytic Virus Therapy

• On October 27, 2015, the FDA approved a new type of immunotherapy—oncolytic virus therapy—for the treatment of advanced melanoma. Talimogene laherparepvec (Imlygic™; T-VEC) is a genetically engineered herpes simplex virus—the virus that causes cold sores. It is injected directly into tumors, where it replicates and causes the tumors to die. This approval is based on a phase III clinical trial, where 16.3% of patients treated with T-VEC achieved a durable response, compared to 2.1% of patients treated with the immune protein GM-CSF.

Monoclonal Antibodies

• Dinutuximab (Unituxin™) was approved on March 10, 2015, for children with high-risk neuroblastoma. Neuroblastoma is a cancer of immature nerve cells, which is most common in the adrenal glands, which sit above the kidneys (although neuroblastoma can develop anywhere that groups of nerve cells exist). It is the most common solid cancer in childhood, with approximately 700 cases occurring in the U.S. each year. Even with aggressive treatment, only 40% to 50% of patients with high-risk neuroblastoma survive. Dinutuximab binds to GD2, which is expressed on the surface of neuroblastoma cells. The FDA approval is based on a phase III clinical trial where 63% of participants receiving the dinutuximab combination were alive and free of tumor growth or recurrence, compared to 46% of participants treated with a vitamin A-related compound, which is commonly used to treat this type of cancer, alone.

• On April 24, 2015, ramucirumab (Cyramza®) was approved for patients with colorectal cancer. It is directed against VEGFR2, and works by blocking the binding of it to VEGF, which is crucial in angiogenesis—the transition of tumors from a benign state to a malignant one characterized by the formation of new blood vessels. A statistically significant overall survival improvement was observed in patients receiving ramucirumab plus chemotherapy (13.3 months), compared to those just receiving chemo alone (11.7 months).

• Multiple myeloma patients got some good news on November 16, 2015—the immunotherapy daratumumab (Darzalex®) was given approval by the FDA for the treatment of patients with multiple myeloma. It was the first monoclonal antibody ever approved for multiple myeloma and is the first approved immunotherapy that targets CD38—a protein found in most multiple myeloma cells. By going after CD38, daratumumab attacks and kills the myeloma cells. In one clinical trial, daratumumab demonstrated a 36% overall response rate in 42 patients with multiple myeloma. Daratumumab also induced durable responses that improved over time, with 65% of responding patients in remission at 12 months. This is really big news for multiple myeloma patients who have become resistant to treatment, which—until now—had a survival of less than a year.

• Necitumumab (Portrazza™) was approved on November 24, 2015, for patients with squamous non-small cell lung cancer, which accounts for 15% of the NSCLC population. Necitumumab blocks the activity of EGFR, a protein commonly found on squamous NSCLC tumors. This approval is based on a clinical trial that compared chemotherapy plus necitumumab to chemotherapy alone. Those taking necitumumab lived longer on average (11.5 months), compared to those taking a chemotherapy regimen (9.9 months). It is the first EGFR antagonist to be approved for lung cancer by the FDA.

• Within just two weeks of daratumumab’s approval, the FDA approved elotuzumab (Empliciti™) for patients with multiple myeloma (November 30, 2015). Elotuzumab targets the SLAMF7 receptor, which is present on both myeloma cells and the immune system’s natural killer (NK) cells. By attaching to the myeloma cells, it marks them for destruction, and by attaching to the NK cells, it primes the immune cells to search for and attack the myeloma cells. The FDA approval is based on the results of a phase III trial in which elotuzumab led to a 30% reduction in the risk of disease progression and death. After two years on the elotuzumab regimen, 41% of patients survived without disease progression, compared to 27% of those without the drug.

2015 was a great year for cancer immunotherapy, and we expect it to be the same in 2016 and beyond, with more treatments—therapeutic vaccines, CAR T cell therapy—joining the list. Stay tuned!