Ipilimumab Clinical Trials

What Is Ipilimumab?

Ipilimumab is an FDA-approved medication for treating certain types of cancer, including advanced melanoma, non-small cell lung cancer, and renal cell carcinoma. It is also approved for classical Hodgkin's lymphoma. Ipilimumab is an antibody that works by targeting CTLA-4, a molecule on immune cells that normally helps to shut down the immune response. By blocking CTLA-4, ipilimumab helps to unleash the body's immune system to fight cancer cells. This type of drug is known as an immune checkpoint inhibitor.

In addition to its approved uses, ipilimumab is being investigated in clinical trials for other conditions such as prostate cancer and pancreatic cancer. It is often studied in combination with other immunotherapies, like nivolumab, or with other cancer treatments such as chemotherapy or radiation therapy.

Uses and Conditions Under Study

Ipilimumab is extensively studied across a wide range of cancers, primarily focusing on its role as an immune checkpoint inhibitor.

• Melanoma: Ipilimumab is FDA-approved for advanced melanoma and is being investigated in 109 trials for melanoma, 59 trials for metastatic melanoma, 18 trials for unresectable melanoma, and 15 trials for malignant melanoma. It aims to enhance the immune system's ability to recognize and attack melanoma cells, often in combination with other immunotherapies or radiation. Studies include NCT02374242, which evaluated ipilimumab with nivolumab for brain metastases.
• Lung Cancer: The drug is approved for non-small cell lung cancer (NSCLC) and is being studied in 18 trials for NSCLC and 15 trials for lung cancer. It is explored alone or in combination with other treatments to improve outcomes for patients with advanced or metastatic lung cancers.
• Kidney Cancer: Ipilimumab is approved for renal cell carcinoma (RCC) and is being investigated in 24 trials for RCC and 15 trials for Stage IV Renal Cell Cancer. Clinical trials assess its safety and effectiveness, often in combination with other drugs like nivolumab or cabozantinib, for metastatic clear cell renal cell carcinoma.
• Prostate Cancer: There are 17 trials investigating ipilimumab for prostate cancer. Studies explore its impact on the immune system in patients receiving hormone therapy, and in combination with nivolumab for metastatic castration-resistant prostate cancer, as seen in NCT04000617.
• Pancreatic Cancer: Ipilimumab is being studied in 15 trials for pancreatic cancer. Research includes combinations with vaccines or other agents to improve the poor prognosis of pancreatic ductal adenocarcinoma.

Other conditions under investigation include classical Hodgkin's lymphoma, where ipilimumab is studied for relapsed or refractory cases, and various solid tumors where it is combined with other investigational agents to assess safety and efficacy.

Dosing

Ipilimumab is administered intravenously (IV). The specific dosage and regimen depend on the condition being treated and whether it is used alone or in combination with other therapies.

In clinical trials, various doses of ipilimumab have been investigated:

• Commonly studied doses include 1 mg/kg, 3 mg/kg, and 10 mg/kg. For example, in some Phase I trials, participants received ipilimumab IV at doses of 2.5 mg, 5 mg, or 10 mg, with dose escalation to determine the recommended Phase II dose.
• In studies for advanced melanoma, doses such as 10 mg/kg have been used, sometimes in combination with other treatments like high-dose interferon.
• When combined with other immunotherapies, such as nivolumab, ipilimumab doses like 1 mg/kg or 3 mg/kg are frequently explored. For instance, a study for advanced solid tumors investigated ipilimumab at 1 mg/kg in combination with other agents to determine recommended Phase II dosing.
• Some trials also explore fixed doses, such as Ipilimumab 25 mg, often in combination with radiation therapy.

Ipilimumab is often given as part of a treatment cycle, with specific schedules for administration, which may include neoadjuvant (before surgery) or adjuvant (after surgery) approaches, or as part of ongoing maintenance therapy.

Side Effects

In clinical trials involving over 5,000 patients, the most commonly reported side effect for Ipilimumab was diarrhea. Approximately 33.9% of patients taking Ipilimumab experienced diarrhea, compared to 22.2% of patients on placebo. Other common side effects included:

• Fatigue: 32.4% of patients on Ipilimumab experienced fatigue, compared to 28.5% on placebo.
• Nausea: 27.7% of patients on Ipilimumab experienced nausea, compared to 25.2% on placebo.
• Pruritus (itching): 25.3% of patients on Ipilimumab experienced pruritus, compared to 12.5% on placebo.
• Decreased appetite: 23.4% of patients on Ipilimumab experienced decreased appetite, compared to 16.5% on placebo.
• Rash: 22.4% of patients on Ipilimumab experienced a rash, compared to 10.8% on placebo.
• Pyrexia (fever): 15.1% of patients on Ipilimumab experienced pyrexia, compared to 9.3% on placebo.
• Increased alanine aminotransferase (a liver enzyme): 14.6% of patients on Ipilimumab experienced an increase, compared to 6.9% on placebo.

Some side effects were observed less frequently with Ipilimumab than with placebo, such as anemia (17.7% on Ipilimumab vs. 20.1% on placebo). It is important to discuss any side effects with your healthcare provider.

Clinical Trial Results

Clinical trials have evaluated Ipilimumab in various cancer types, assessing its impact on survival, tumor response, and other clinical measures.

Melanoma

In a study (NCT00162123) evaluating Ipilimumab reinduction regimens in patients with melanoma, different dosing strategies showed varying outcomes:

• Overall Survival (OS): The median overall survival was 30.8 months for patients receiving 10 mg/kg Ipilimumab, 18.7 months for those on 3 to 10 mg/kg Ipilimumab, and 15.2 months for patients on 0.3 to 10 mg/kg Ipilimumab.
• 1-Year Survival Rates: Approximately 63.6% of patients on 10 mg/kg Ipilimumab were alive at one year, compared to 65.6% on 0.3 to 10 mg/kg Ipilimumab, and 38.2% on 3 to 10 mg/kg Ipilimumab.
• Progression-Free Survival (PFS): The median time patients lived without their disease worsening was 3.4 months for the 10 mg/kg Ipilimumab regimen, and 2.6 months for both the 0.3 to 10 mg/kg and 3 to 10 mg/kg Ipilimumab regimens.

Another study (NCT00084656) in patients with resected Stage III or Stage IV melanoma investigated immune-related adverse events (irAEs), which are side effects related to the immune system's activity. The percentage of participants experiencing irAEs was 65.4% for 10 mg/kg Ipilimumab alone, 72.0% for 10 mg/kg Ipilimumab combined with peptides, and 80.0% for 3.0 mg/kg Ipilimumab combined with peptides.

Lymphoma

In a study (NCT00089076) of patients with recurrent or refractory lymphoma, Ipilimumab led to confirmed responses (complete or partial) in 2 participants.

Pancreatic Cancer

A trial (NCT00112580) for patients with Stage IV pancreatic cancer that could not be surgically removed found that 0% of participants achieved a complete or partial response to Ipilimumab, in both locally advanced and metastatic disease cohorts.

Synovial Sarcoma

In a study (NCT00140855) of patients with advanced synovial sarcoma, no participants achieved a complete or partial tumor response. However, 6 participants showed stable disease, meaning their tumors did not grow or shrink significantly.

Currently Recruiting Trials

Where to Participate

• Las Vegas, Nevada (63 sites)
• New York, New York (36 sites)
• St Louis, Missouri (32 sites)
• Pittsburgh, Pennsylvania (29 sites)
• Chicago, Illinois (27 sites)
• Columbus, Ohio (25 sites)
• Boston, Massachusetts (24 sites)
• Atlanta, Georgia (23 sites)
• Anchorage, Alaska (23 sites)
• Los Angeles, California (22 sites)

Development Timeline