Ipilimumab +/− Interferon Alfa-2b for Advanced Skin Cancer

Not currently recruiting at 324 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: Corticosteroids, Immunosuppressants

Disqualifiers: Autoimmune disorders, Active infection, Pregnancy, 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: 15

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of the drug ipilimumab, with or without interferon alfa-2b, in treating advanced skin cancer that cannot be surgically removed. Ipilimumab, a monoclonal antibody, targets certain cells to block tumor growth, while interferon alfa-2b may disrupt cancer cell growth. The trial aims to determine if combining these treatments is more effective than using ipilimumab alone. Individuals diagnosed with advanced melanoma that cannot be surgically removed and who have had no more than one prior treatment for this cancer may be suitable for this trial. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial requires a 4-week washout period (time without taking certain medications) between your last treatment and the start of the study therapy. If you are on systemic corticosteroids or other immunosuppressants, you must stop them at least 2 weeks before joining the trial, unless they are replacement doses for adrenal insufficiency.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that ipilimumab, when used alone, can help treat advanced melanoma. Safety data from 1,498 patients who took different doses of ipilimumab suggest it is generally well-tolerated. However, some patients experienced immune-related side effects, such as skin rashes and diarrhea.

Studies indicate that combining ipilimumab with high-dose recombinant interferon alfa-2b can lead to more severe reactions. Both treatments can cause side effects, but using them together may increase the risk of these adverse effects. While ipilimumab has been extensively studied, more research is needed to fully understand the safety of combining it with interferon alfa-2b. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for advanced skin cancer because they explore different dosing strategies and combinations of ipilimumab, with or without interferon alfa-2b. Ipilimumab is an immune checkpoint inhibitor that works by enhancing the body's immune response against cancer cells, which is different from traditional chemotherapy that directly attacks cancer cells. The combination with interferon alfa-2b, which boosts the immune system, might enhance this effect even further. By testing both higher and lower doses of ipilimumab, alone or with interferon, researchers aim to find the most effective and tolerable approach, potentially offering new hope for patients with advanced skin cancer.

What evidence suggests that this trial's treatments could be effective for advanced skin cancer?

Research shows that ipilimumab can help treat advanced melanoma, a type of skin cancer. In this trial, participants will receive different treatments involving ipilimumab. Some will receive a higher dose, which studies have found can extend survival to an average of 15.7 months, though it may also cause more side effects. Others will receive a lower dose. Additionally, some participants will receive ipilimumab combined with recombinant interferon alfa-2b, which may enhance the immune system's ability to fight cancer cells. Interferon alfa-2b alone has been shown to reduce the chance of cancer recurrence and improve survival without requiring a higher dose. These findings suggest that ipilimumab, either alone or with interferon alfa-2b, could be a promising treatment for advanced melanoma. ^{2 6 7 8 9}

Who Is on the Research Team?

Ahmad Tarhini

Principal Investigator

ECOG-ACRIN Cancer Research Group

Are You a Good Fit for This Trial?

This trial is for adults with stage III-IV melanoma that can't be surgically removed. Eligible participants must not have other current cancers (except certain cases), no brain metastasis, normal organ function tests, and no history of severe autoimmune diseases or conditions requiring systemic steroids. Women who can bear children and men must use effective contraception.

Inclusion Criteria

I haven't received any vaccines for infectious diseases in the last 4 weeks.

Your white blood cell count is at least 3000 per microliter.

My cancer's size and spread were checked within the last month.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction

Patients receive ipilimumab and possibly recombinant interferon alfa-2b depending on the arm, with treatments administered over several weeks

12 weeks

Multiple visits for IV and SC administration

Maintenance

Continued administration of ipilimumab and possibly recombinant interferon alfa-2b, with treatments spaced out over a longer period

48 weeks

Regular visits every 12 weeks for IV administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 10 years

Every 3 months for 2 years, then every 6 months for 3 years, then annually

What Are the Treatments Tested in This Trial?

Interventions

• Ipilimumab
• Recombinant Interferon Alfa-2b

Trial Overview The study is testing the effectiveness of ipilimumab alone versus in combination with high-dose recombinant interferon alfa-2b in treating advanced melanoma. Ipilimumab is a monoclonal antibody that may block tumor growth by targeting specific cells, while interferon alfa-2b could interfere with tumor cell growth.

How Is the Trial Designed?

Group I: Arm D (lower dose ipilimumab) Experimental Treatment 2 Interventions

INDUCTION PHASE: Patients receive lower dose ipilimumab IV over 90 minutes once every 3 weeks for 4 doses. MAINTENANCE PHASE: Patients receive lower dose ipilimumab IV over 90 minutes once every 12 weeks for 4 doses beginning in week 24.

Group II: Arm C (lower dose ipilimumab + HDI) Experimental Treatment 3 Interventions

INDUCTION PHASE: Patients receive lower dose ipilimumab IV over 90 minutes once every 3 weeks for 4 doses and recombinant interferon alfa-2b IV over 20 minutes 5 days a week for 4 weeks and then SC 3 times weekly for 8 weeks. MAINTENANCE PHASE: Patients receive lower dose ipilimumab IV over 90 minutes once every 12 weeks for 4 doses beginning in week 24 and recombinant interferon alfa-2b SC 3 times weekly for 48 weeks.

Group III: Arm B (higher dose ipilimumab) Experimental Treatment 2 Interventions

INDUCTION PHASE: Patients receive higher dose ipilimumab IV over 90 minutes once every 3 weeks for 4 doses. MAINTENANCE PHASE: Patients receive higher dose ipilimumab IV over 90 minutes once every 12 weeks for 4 doses beginning in week 24.

Group IV: Arm A (higher dose ipilimumab, HDI) Experimental Treatment 3 Interventions

INDUCTION PHASE: Patients receive higher dose ipilimumab IV over 90 minutes once every 3 weeks for 4 doses and recombinant interferon alfa-2b IV over 20 minutes 5 days a week for 4 weeks and then SC 3 times weekly for 8 weeks. MAINTENANCE PHASE: Patients receive higher dose ipilimumab IV over 90 minutes once every 12 weeks for 4 doses beginning in week 24 and recombinant interferon alfa-2b SC 3 times weekly for 48 weeks.

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+

Published Research Related to This Trial

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 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]

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 is a monoclonal antibody that enhances T cell activation by blocking the CTLA-4 receptor, leading to improved antitumor responses and has been shown to increase overall survival in patients with advanced melanoma, a condition with a poor prognosis.

While ipilimumab has demonstrated significant efficacy, it can cause serious immune-related adverse effects that require prompt management, highlighting the importance of monitoring patients during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ipilimumab: a novel immunostimulatory monoclonal antibody for the treatment of cancer. Graziani, G., Tentori, L., Navarra, P.[2020]

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]

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, an immunotherapy for metastatic melanoma, can cause serious but rare haematological adverse events like anaemia and leukopenia in some patients, as seen in three cases presented in the study.

These haematological toxicities, while potentially severe, are manageable and can be effectively treated with corticosteroids, highlighting the importance of prompt recognition and intervention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Serious haematological toxicity during and after ipilimumab treatment: a case series. Simeone, E., Grimaldi, AM., Esposito, A., et al.[2021]

Citations

1. nejm.org nejm.org/doi/full/10.1056/NEJMoa1910836

Five-Year Survival with Combined Nivolumab and ... Overall survival at 5 years was 52% in the nivolumab-plus-ipilimumab group and 44% in the nivolumab group, as compared with 26% in the ipilimumab group.

2. news.bms.com news.bms.com/news/details/2021/Six-and-a-Half-Year-Outcomes-for-Opdivo-nivolumab-in-Combination-with-Yervoy-ipilimumab-Continue-to-Demonstrate-Durable-Long-Term-Survival-Benefits-in-Patients-with-Advanced-Melanoma/default.aspx

Six-and-a-Half-Year Outcomes for Opdivo (nivolumab) in ... Among patients with BRAF-mutant tumors, the rate of OS at 6.5 years was 57% in patients who received Opdivo plus Yervoy, 43% for Opdivo alone, ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9954703/

Immunotherapy in Melanoma: Recent Advances and ... A dose of 10 mg/kg demonstrated improved overall survival (median overall survival 15.7 months vs.

4. opdivo.com opdivo.com/melanoma/clinical-trial-results/advanced-immunotherapy-combination

Advanced Melanoma Skin Cancer | Clinical Trial Results See how OPDIVO® (nivolumab) + YERVOY® (ipilimumab) performed in a clinical trial as a treatment for people with advanced melanoma skin cancer that has ...

5. targetedonc.com targetedonc.com/view/higher-dose-of-ipilimumab-improves-survival-but-increases-toxicities-in-advanced-melanoma

Higher Dose of Ipilimumab Improves Survival, But ... Higher Dose of Ipilimumab Improves Survival, But Increases Toxicities in Advanced Melanoma. Author(s)Jason Harris. According to results from a ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/20147741/

Efficacy and safety of ipilimumab monotherapy in patients ... Conclusion: Ipilimumab demonstrated clinical activity with encouraging long-term survival in a previously treated advanced melanoma population.

7. ascopubs.org ascopubs.org/doi/10.1200/jco.2011.29.15_suppl.8583

Ipilimumab safety profile: Summary of findings from ... Safety data were pooled from 1498 patients treated with ipilimumab at various doses, alone and in combination with various agents, and AEs in ...

8. merck.com merck.com/news/ten-year-data-for-mercks-keytruda-pembrolizumab-demonstrates-sustained-overall-survival-benefit-versus-ipilimumab-in-advanced-melanoma/

Ten-Year Data for Merck's KEYTRUDA® (pembrolizumab ... At 10 years, more than one-third (34.0%) of patients with advanced melanoma were alive after treatment with KEYTRUDA, compared to 23.6% of patients treated ...

9. news.bms.com news.bms.com/news/details/2024/Bristol-Myers-Squibb-Presents-Landmark-10-Year-Follow-Up-Data-from-CheckMate--067-Which-Showed-Continued-Durable-Long-Term-Survival-Benefit-with-Opdivo-plus-Yervoy-in-Advanced-Melanoma/default.aspx

067 Which Showed Continued Durable Long-Term ... With a minimum follow up of 10 years, median overall survival (OS) was 71.9 months with Opdivo plus Yervoy (95% CI: 38.2-114.4) - the longest ...