Ipilimumab +/− Sargramostim for Skin Cancer

Recruiting at 295 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: Systemic steroids, Interleukin 2

Disqualifiers: CNS metastases, Autoimmune disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 6

245 Participants Needed

Trial Summary

What is the purpose of this trial?

This randomized phase II trial is studying how well giving ipilimumab with or without sargramostim (GM-CSF) works in treating patients with stage III or stage IV melanoma that cannot be removed by surgery (unresectable). Ipilimumab works by activating the patient's immune system to fight cancer. Colony-stimulating factors, such as sargramostim, may increase the number of immune cells found in bone marrow or peripheral blood and may help the immune system recover from the side effects of treatment. It is not yet known whether giving ipilimumab together with sargramostim is more effective than ipilimumab alone in treating melanoma.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications, such as systemic corticosteroids, at least 4 weeks before starting. If you're on medications like interleukin 2, interferon, or other immunotherapy regimens, you will also need to stop those. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug Ipilimumab for treating skin cancer?

Research shows that Ipilimumab, a drug that helps the immune system fight cancer, has been effective in improving survival for patients with advanced melanoma, a type of skin cancer. In clinical trials, patients treated with Ipilimumab lived longer compared to those who did not receive the drug. ^{1 2 3 4 5}

Is the combination of Ipilimumab and Sargramostim safe for humans?

Ipilimumab, also known as Yervoy, has been studied for its safety in treating advanced melanoma. Most people experience mild to moderate side effects, but some may have severe reactions. It's important to monitor patients closely and manage side effects promptly, often with medications like corticosteroids. ^{2 4 6 7 8}

What makes the drug Ipilimumab unique for treating skin cancer?

Ipilimumab is unique because it is a monoclonal antibody that targets CTLA-4, a molecule that normally helps keep the immune system in check. By blocking CTLA-4, Ipilimumab boosts the body's immune response against cancer cells, which can lead to longer-lasting tumor regression compared to other treatments. ^{2 3 4 9 10}

Research Team

Frank S Hodi

Principal Investigator

ECOG-ACRIN Cancer Research Group

Eligibility Criteria

This trial is for adults with advanced melanoma that can't be surgically removed. They must have a certain level of white blood cells, no HIV or hepatitis infections, and be in good physical condition (ECOG 0-1). Women who could get pregnant must use effective birth control. Participants cannot have brain metastases, autoimmune diseases, or a history of certain treatments like ipilimumab.

Inclusion Criteria

I do not have an active hepatitis B infection.

Your AST and ALT levels are not more than 2.5 times the upper limit of normal.

I am not currently on treatments like IL2, interferon, chemotherapy, or steroids.

Exclusion Criteria

I do not have an autoimmune disease, or if I have thyroid issues, they are stable with treatment.

I have never been treated with ipilimumab or drugs targeting CD137 or CTLA-4.

I do not have any health or mental conditions that could make treatment risky.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction Treatment

Patients receive induction therapy with ipilimumab and sargramostim or ipilimumab alone. Treatment repeats every 21 days for 4 cycles.

12 weeks

4 visits (in-person)

Maintenance Therapy

Patients receive maintenance therapy with ipilimumab and sargramostim or ipilimumab alone. Treatment with ipilimumab repeats every 12 weeks and sargramostim every 21 days.

12 weeks

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment completion. Follow-up occurs every 3 months for 2 years, then every 6 months for 3 years.

5 years

Treatment Details

Interventions

• Ipilimumab
• Sargramostim

Trial Overview The study is testing if combining the immune system booster Ipilimumab with Sargramostim (GM-CSF), which helps grow more immune cells, works better than Ipilimumab alone for treating unresectable stage III/IV melanoma. Patients are randomly assigned to one of the two treatment groups.

Participant Groups

Group I: Arm A (ipilimumab and sargramostim) Experimental Treatment 2 Interventions

Patients receive induction therapy comprising ipilimumab IV over 90 minutes on day 1 and sargramostim SC once daily on days 1-14. Treatment repeats every 21 days for 4 cycles. After 12 weeks of induction treatment, anti-tumor response is assessed and patients then receive maintenance therapy comprising ipilimumab IV over 90 minutes on day 1 and sargramostim SC once daily on days 1-14. Treatment with ipilimumab repeats every 12 weeks and treatment with sargramostim repeats every 21 days. After 12 weeks of maintenance therapy, anti-tumor response is reassessed and patients with responsive or stable disease then continue maintenance therapy until disease progression or unacceptable toxicity.

Group II: Arm B (ipilimumab) Active Control 1 Intervention

Patients receive induction therapy comprising ipilimumab IV over 90 minutes on day 1. Treatment repeats every 21 days for 4 cycles. After 12 weeks of induction treatment, anti-tumor response is assessed and patients then receive maintenance therapy of ipilimumab IV over 90 minutes on day 1. Treatment with ipilimumab repeats every 12 weeks. After 12 weeks of maintenance therapy, anti-tumor response is reassessed and cycles repeat every 12 weeks in the absence of disease progression or unacceptable toxicity

Ipilimumab is already approved in United States, European Union for the following indications:

Approved in United States as Yervoy for:

• Advanced melanoma
• Stage III unresectable melanoma
• Stage IV metastatic melanoma

Approved in European Union as Yervoy for:

• Advanced melanoma
• Stage III unresectable melanoma
• Stage IV metastatic melanoma

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Findings from Research

Ipilimumab, a first-in-class T-cell potentiator, has shown significant improvements in overall survival for advanced melanoma patients in a phase 3 trial, with median survival extending to 10.1 months compared to 6.4 months for the control group.

The treatment demonstrated long-term survival benefits, with 24-month survival rates increasing from 13.7% with the gp100 vaccine alone to 21.6% and 23.5% for patients receiving ipilimumab alone or in combination, respectively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Releasing the brake on the immune system: ipilimumab in melanoma and other tumors. Tarhini, A., Lo, E., Minor, DR.[2021]

Ipilimumab (Yervoy) is the first new therapy approved for melanoma in over a decade, functioning as an antibody that blocks CTLA-4, which enhances the immune response against tumors, leading to durable tumor regression and improved overall survival in patients with advanced melanoma.

The clinical development of ipilimumab revealed its unique side effects profile and the long-lasting nature of its therapeutic responses, paving the way for future combination therapies with other checkpoint inhibitors currently being tested.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunomodulatory therapy for melanoma: ipilimumab and beyond. Callahan, MK., Postow, MA., Wolchok, JD.[2021]

Ipilimumab (Yervoy®) is an approved monoclonal antibody for treating malignant melanoma by blocking the CTLA-4 protein, which enhances T-cell responses against tumor cells, showing its efficacy in cancer immunotherapy.

Currently, ipilimumab is also being tested in phase III trials for prostate cancer and phase II trials for non-small cell lung cancer, indicating its potential for broader applications in cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ipilimumab: first global approval. Cameron, F., Whiteside, G., Perry, C.[2021]

Ipilimumab significantly improves overall survival in patients with advanced melanoma compared to the gp100 peptide vaccine, reducing the risk of death by 34% with monotherapy and 32% when combined with the vaccine.

The treatment can cause unique immune-related side effects, particularly affecting the skin and gastrointestinal system, which require careful monitoring and management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ipilimumab: a guide to its use in advanced melanoma. Lyseng-Williamson, KA., Sanford, M.[2017]

In a phase 2 trial involving 142 patients with untreated advanced melanoma, the combination of nivolumab and ipilimumab resulted in a 2-year overall survival rate of 63.8%, compared to 53.6% for those receiving ipilimumab alone, suggesting improved survival outcomes with the combination therapy.

However, the combination treatment was associated with a higher incidence of severe side effects, with 54% of patients experiencing grade 3-4 adverse events compared to 20% in the ipilimumab-only group, indicating a trade-off between efficacy and safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined nivolumab and ipilimumab versus ipilimumab alone in patients with advanced melanoma: 2-year overall survival outcomes in a multicentre, randomised, controlled, phase 2 trial. Hodi, FS., Chesney, J., Pavlick, AC., et al.[2022]

Ipilimumab showed a best overall response rate (BORR) of 5.8% and a disease control rate (DCR) of 27% in patients with advanced melanoma, indicating some level of efficacy in this challenging population.

The treatment resulted in promising long-term survival rates, with 1- and 2-year survival rates of 47.2% and 32.8%, respectively, and a median overall survival of 10.2 months, while adverse events were primarily immune-related but manageable.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of ipilimumab monotherapy in patients with pretreated advanced melanoma: a multicenter single-arm phase II study. O'Day, SJ., Maio, M., Chiarion-Sileni, V., et al.[2022]

Ipilimumab has shown a positive impact on overall survival in patients with stage IV melanoma, with long-term follow-up indicating its effectiveness compared to conventional treatments.

While 84.8% of patients experience drug-related adverse events, most are mild to moderate; however, severe reactions can occur, necessitating careful monitoring and management, especially when combined with other therapies like vemurafenib.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CTLA-4 blockade with ipilimumab: biology, safety, efficacy, and future considerations. Camacho, LH.[2022]

Ipilimumab, an anti-CTLA-4 antibody, has been shown to improve survival in patients with unresectable or metastatic melanoma, with a standard dosing of 3 mg/kg every 3 weeks for a total of 4 doses.

While ipilimumab can cause immune-related adverse events in 15% of patients, most are mild and manageable; however, high-grade events can be serious and require careful monitoring and treatment with corticosteroids.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ipilimumab for advanced melanoma: a pharmacologic perspective. Trinh, VA., Hagen, B.[2021]

Ipilimumab, a monoclonal antibody targeting CTLA-4, has shown potential activity in prostate cancer, particularly in patients with lower disease burden, despite not improving overall survival in a Phase III study.

While immune-related adverse events are common with ipilimumab treatment, they can generally be managed effectively using standard immunosuppressive treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ipilimumab in the treatment of prostate cancer. Reese, Z., Straubhar, A., Pal, SK., et al.[2018]

Ipilimumab, a monoclonal antibody used to enhance anti-tumor T-cell responses, can cause significant side effects, including ipilimumab-induced hypophysitis (IH), which affects hormone levels and requires hormone replacement therapy in most cases.

In a review of 10 patients with IH, early detection and management guidelines were developed, highlighting the importance of monitoring hormone levels and recognizing imaging abnormalities, which often resolve without high-dose glucocorticoid therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ipilimumab-induced hypophysitis in melanoma patients: an Australian case series. Lam, T., Chan, MM., Sweeting, AN., et al.[2022]

References

1. United States pubmed.ncbi.nlm.nih.gov

Releasing the brake on the immune system: ipilimumab in melanoma and other tumors. [2021]

2. United States pubmed.ncbi.nlm.nih.gov

Immunomodulatory therapy for melanoma: ipilimumab and beyond. [2021]

3. New Zealand pubmed.ncbi.nlm.nih.gov

Ipilimumab: first global approval. [2021]

4. New Zealand pubmed.ncbi.nlm.nih.gov

Ipilimumab: a guide to its use in advanced melanoma. [2017]

5. England pubmed.ncbi.nlm.nih.gov

Combined nivolumab and ipilimumab versus ipilimumab alone in patients with advanced melanoma: 2-year overall survival outcomes in a multicentre, randomised, controlled, phase 2 trial. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of ipilimumab monotherapy in patients with pretreated advanced melanoma: a multicenter single-arm phase II study. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

CTLA-4 blockade with ipilimumab: biology, safety, efficacy, and future considerations. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Ipilimumab for advanced melanoma: a pharmacologic perspective. [2021]

9. England pubmed.ncbi.nlm.nih.gov

Ipilimumab in the treatment of prostate cancer. [2018]

10. Australia pubmed.ncbi.nlm.nih.gov

Ipilimumab-induced hypophysitis in melanoma patients: an Australian case series. [2022]