Nivolumab and Ipilimumab Clinical Trials

Advances in Immunotherapy drugs are showing great promise in treating difficult cancers like mesothelioma. Trials using a combination of drugs that boost the action of the immune system are ongoing and have already shown some successes. Currently there is a phase III clinical trial testing the effectiveness of nivolumab and ipilimumab in patients with pleural mesothelioma. It is being compared to standard chemotherapy with platinum drugs and pemetrexed.

Nivolumab

Made by Bristol-Myers Squibb, nivolumab is an immunotherapy drug given the brand name Opdivo. It has been tested in a number of clinical trials already and is approved for treating specific types of cancer. Current clinical trials are looking at the effectiveness and safety of nivolumab in patients with mesothelioma, usually in combination with other drugs. Nivolumab is approved by the U.S. Food and Drug Administration to treat specific advanced and metastasized cancers including:

• Certain types of melanoma. It is also approved to prevent the recurrence of melanoma in some patients.
• Non-small cell and small cell lung cancer.
• Renal cell carcinoma.
• Hodgkin’s lymphoma.
• Head and neck cancer.
• Urothelial cancer.
• Colorectal cancer.
• Hepatocellular carcinoma.

There is hope that this drug will prove in clinical trials to also be useful in treating advanced mesothelioma and to be approved for that purpose.

Nivolumab works by binding to a protein on immune system T-cells. The protein, PD-1, interacts with proteins on cancer cells, which tells it not to attack. The drug interferes with this interaction, which takes the brakes off the immune system and allows it to recognize the cancer cells as abnormal.

Ipilimumab

Marketed under the brand name Yervoy, ipilimumab is also made by Bristol-Myers Squibb and is also an immunotherapy drug. It works in a similar way to Opdivo. Ipilimumab targets the protein CTLA-4 on T-cells. This protein acts like an off switch for the immune cells. The drug blocks it and keeps the cells in the “on” state so they can attack and kill cancer cells.

Ipilimumab is not approved to treat as many cancers as nivolumab. Currently on that list is metastatic melanoma and as an additional therapy for melanoma patients who have undergone surgery to remove tumors. It is also approved to treat renal cell carcinoma, and certain types of colorectal cancer.

Combination Phase III Clinical Trial

These two drugs are approved for treating a limited number of cancer types, but patients with other kinds of cancers can potentially access them through clinical trials. For mesothelioma patients there are ongoing trials using both drugs in combination, and there may be other trials in the future.

Right now the combination therapy is being used in a phase III clinical trial. The participants in the trial are mesothelioma patients with cancers that are unresectable, which means they are not candidates for surgical removal of the bulk of tumors. The participants have also not had any other treatment; the experimental combination of nivolumab and ipilimumab is being used as a first-line therapy.

In this phase III trial patients are randomized, with some getting the new therapy and others getting the standard chemotherapy treatment of pemetrexed with carboplatin or cisplatin. It is necessary to use both types of treatment to make a comparison between the standard therapy and the new one.

Patients were accepted into the trial that were at least 18 years old and diagnosed with pleural mesothelioma, did not qualify for curative surgery, did not have another type of cancer, had metastasis to the central nervous system, and had not yet received any chemotherapy.

Earlier Clinical Trial Results with Nivolumab and Ipilimumab

The current phase III trial follows what was a promising phase II trial of the nivolumab and ipilimumab combination. That trial took place with 125 mesothelioma patients in France. That trial used the combination and tested it against the use of nivolumab alone. Another difference from the current trial was that patients in this trial had been given chemotherapy previously but without success.

The researchers achieved a disease control rate of 50 percent. This means that half of the participants had either no additional growth of tumors or actual shrinking in the tumors after several weeks of the combination treatment. More than a quarter of the patients saw tumors get smaller and the overall survival time was longer on the combination.

Potential Side Effects

Clinical trials are used to determine effectiveness of new therapies, but also to find out what side effects are caused and if they are worth the benefits of the treatment. So far, some of the more common side effects reported are hyponatremia, rashes and itchiness, fatigue, liver damage, difficulty breathing, pain, cough, nausea, anemia, constipation, vomiting, and diarrhea.

The current phase III trial is closed to new participants right now, but it may open up in the future. There is also potential that other trials using this immunotherapy combination will begin, allowing for more mesothelioma patients to benefit from it. If the trial goes well the pair of drugs could become an approved therapy for mesothelioma. If you are interested in accessing clinical trials, talk to your medical team to find out if you qualify for any studies that are currently taking patients.