Pre-surgery Immunotherapy for Melanoma

Recruiting at 3 trial locations

Overseen By Michael Postow, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Memorial Sloan Kettering Cancer Center

Must not be taking: Immunosuppressants

Disqualifiers: Autoimmune disease, Hepatitis B, HIV/AIDS, others

Stay on Your Current Meds You can continue your current medications while participating

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

Compensation: Varies

Number of Visits: Unknown

28 Participants Needed

Trial Summary

Do I need to stop my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot participate if you have active autoimmune disease requiring immunosuppression or if you are using other investigational drugs within 30 days before the study.

Do I need to stop my current medications for the trial?

The trial information does not specify whether you need to stop taking your current medications. However, if you are on investigational drugs, you must stop them at least 30 days before starting the study treatment.

What data supports the idea that Pre-surgery Immunotherapy for Melanoma is an effective treatment?

The available research shows that pre-surgery immunotherapy for melanoma, using drugs like immune checkpoint inhibitors, leads to better outcomes compared to standard treatments. Specifically, about 70%-80% of patients remain free from cancer recurrence two years after treatment. This is a significant improvement over traditional methods. Additionally, trials have shown that this approach can make previously inoperable melanomas treatable with surgery, further improving survival rates. These findings suggest that pre-surgery immunotherapy is a promising option for treating melanoma. ^{1 2 3 4 5}

What data supports the effectiveness of the drug Ipilimumab, Yervoy, Nivolumab, and Opdivo for pre-surgery treatment of melanoma?

Research shows that using immune checkpoint inhibitors (drugs that help the immune system attack cancer cells) before surgery can improve outcomes for melanoma patients, with about 70%-80% of patients remaining cancer-free for two years. These drugs have shown promising results in early trials, with some patients experiencing complete responses, meaning no signs of cancer were found after treatment. ^{1 2 3 4 5}

What safety data exists for pre-surgery immunotherapy for melanoma?

Existing safety data for pre-surgery immunotherapy for melanoma includes findings from various studies. A study using a cancer registry identified both known and unknown adverse events (AEs) associated with immunotherapy and targeted therapy in melanoma patients, with a lower incidence of AEs in the anti-PD-1 group. Another study on immune checkpoint inhibitors (ICIs) in the perioperative setting found them to be generally safe, with no Grade III-IV complications reported. Ipilimumab, a CTLA-4 inhibitor, has been associated with AEs in up to 64% of patients, but management strategies have reduced morbidity. Overall, while some AEs are reported, pre-surgery immunotherapy appears to be safe, though further studies are needed to confirm these findings. ^{6 7 8 9 10}

Is pre-surgery immunotherapy for melanoma safe for humans?

Pre-surgery immunotherapy, including drugs like Ipilimumab and Nivolumab, has been studied for safety in humans. While some adverse events (side effects) are common, they are often manageable, and serious complications are less frequent. Overall, these treatments are considered safe, but monitoring for side effects is important. ^{6 7 8 9 10}

Is the treatment Surgical Resection of Melanoma a promising treatment for melanoma?

Surgical resection is a promising treatment for early-stage melanoma because it can completely remove the cancer and often cure the patient. For more advanced melanoma, surgery is still important, but combining it with new drug treatments before surgery can improve outcomes. ^{2 11 12 13 14}

How is the treatment 'Surgical Resection of Melanoma' different from other treatments for melanoma?

This treatment is unique because it involves pre-surgery immunotherapy, using immune checkpoint inhibitors (ICIs) like nivolumab and ipilimumab, which are given before the surgical removal of melanoma. This approach can enhance the body's immune response against the tumor, potentially leading to better outcomes and higher recurrence-free survival rates compared to traditional post-surgery treatments. ^{2 11 12 13 14}

What is the purpose of this trial?

Combination treatment with nivolumab and ipilimumab before surgery may help people with melanoma because the drugs are designed to help the immune system target and destroy cancer cells (immunotherapy), which may shrink the cancer and prevent recurrence after surgery. Treatment given before surgery is called neoadjuvant therapy. The purpose of this study is to find out whether neoadjuvant therapy with nivolumab and ipilimumab can kill melanoma tumors before surgery and prevent disease from coming back after surgery. This study also explores a new, experimental PET scan that images the immune system to see if it is related to treatment outcomes.

Research Team

Michael A. Postow

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

This trial is for adults over 18 with certain stages of melanoma (IIIB, IIIC, IIID, or IV) that can be removed by surgery. Participants must understand the study and agree to its rules. They should have good physical function and not be pregnant or nursing. People who've had specific immunotherapies or suffer from autoimmune diseases, severe allergies to antibodies, HIV/AIDS, hepatitis B infection, or other conditions making treatment risky are excluded.

Inclusion Criteria

I am fully active or can carry out light work.

My cancer's BRAF status does not affect my eligibility.

I understand the study requirements and have signed the consent form.

Exclusion Criteria

I do not have an active autoimmune disease or need for immunosuppression.

I have received immunotherapy targeting CTLA-4 or PD-1/PD-L1 before.

I have an active hepatitis B infection confirmed by a test.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Treatment

Participants receive combination treatment with nivolumab and ipilimumab before surgery to target and destroy melanoma tumors

6-8 weeks

Surgery

Participants undergo surgery to remove melanoma tumors

Follow-up

Participants are monitored for safety and effectiveness after surgery and treatment, including assessment of pathologic response

up to 2 years

Treatment Details

Interventions

• Ipilimumab
• Nivolumab
• PET Scan
• Surgical Resection of Melanoma

Trial Overview The trial tests if combining nivolumab and ipilimumab as pre-surgery (neoadjuvant) therapy helps shrink melanoma tumors and prevent their return post-surgery. It also examines a new PET scan technique to see how well the immune system responds to this treatment.

Participant Groups

Group I: Participants with Stage III Melanoma Experimental Treatment 4 Interventions

All participants will have cytologically or histologically confirmed stage IIIB, IIIC, IIID melanoma that can be surgically removed.

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Findings from Research

Neoadjuvant systemic therapy using immune checkpoint inhibitors shows promise in improving recurrence-free survival for patients with stage III and IV melanoma, potentially outperforming the traditional approach of surgery followed by adjuvant therapy.

Early phase trials indicate that neoadjuvant therapy can lead to pathological complete response rates between 30% and 70%, suggesting it may be an effective strategy, although further studies are needed to determine optimal dosing and timing relative to surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant Immune Checkpoint Inhibitor Therapy in Melanoma: Efficacy, Safety and Timing. van Akkooi, ACJ., Zijlker, LP., Wouters, MWJM.[2022]

Neoadjuvant immune checkpoint inhibitors (ICIs) have shown improved outcomes in melanoma treatment, with 70-80% of patients experiencing recurrence-free survival at 2 years, based on a review of 61 phase II and III trials.

Biomarkers such as higher PD-L1 expression and CD8+ cell density can predict patient responses to ICIs, indicating that these treatments may significantly alter the standard approach for advanced resectable melanoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preoperative Therapy in Melanoma: Evolving Perspectives in Clinical Trials. Kakish, H., Xu, K., Ahmed, FA., et al.[2023]

In a study of 9800 patients with stage IV melanoma, only 22% underwent surgery, and those who did were generally younger, had private insurance, and were treated at academic centers, indicating that access to surgery may be influenced by socioeconomic factors.

Patients receiving both surgery and immunotherapy had significantly better overall survival rates compared to those who received neither treatment, highlighting the potential benefits of combining these approaches in managing advanced melanoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Surgical Utilization and Outcomes for Patients with Stage IV Melanoma in the Modern Immunotherapy Era. Lwin, TM., Kaelberer, Z., Ruan, M., et al.[2023]

In a study of 14,433 patients with stage IV melanoma, it was found that the introduction of immunotherapy, particularly checkpoint inhibitors, did not significantly change the rates of surgical resection for metastatic disease compared to the period before these treatments were available.

The analysis revealed that patients receiving immunotherapy were generally younger, healthier, and had better socioeconomic status, indicating disparities in access to treatment among different patient groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of immunotherapy and surgery for stage IV melanoma. Molina, G., Kasumova, GG., Qadan, M., et al.[2021]

Immunotherapy has significantly changed how melanoma is treated, influencing surgical decisions for both resectable and unresectable cases, which may lead to increased surgical interventions for metastatic melanoma.

While immunotherapies show great promise in controlling melanoma, further research is necessary to enhance their effectiveness while reducing potential side effects for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current Immunotherapy Practices in Melanoma. Rothermel, LD., Sarnaik, AA., Khushalani, NI., et al.[2020]

Ipilimumab, a treatment for metastatic melanoma, can cause adverse events (AEs) in up to 64% of patients, including rare and potentially life-threatening conditions like DRESS and aseptic meningitis, highlighting the need for careful monitoring and management of side effects.

Despite the occurrence of severe AEs, ipilimumab showed a high response rate in patients, with 30.9% experiencing tumor regression and a 61.8% tumor control rate, suggesting that effective antitumor responses can occur even with limited treatment exposure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The price of tumor control: an analysis of rare side effects of anti-CTLA-4 therapy in metastatic melanoma from the ipilimumab network. Voskens, CJ., Goldinger, SM., Loquai, C., et al.[2022]

A systematic review of 18 studies on neoadjuvant immune checkpoint inhibitors (ICIs) for early-stage non-small-cell lung cancer (NSCLC) suggests that these treatments are generally safe and well tolerated, with low 30-day mortality rates (0% to 5.4%) and no significant adverse events reported as the main cause for surgery cancellations.

Surgery cancellation rates varied widely (0% to 45.8%), primarily due to disease progression rather than treatment-related adverse events, indicating that while ICIs are promising, careful monitoring of disease status is crucial before surgical intervention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of Neoadjuvant Immune Checkpoint Inhibitors on Surgery and Perioperative Complications in Patients With Non-small-cell Lung Cancer: A Systematic Review. Takada, K., Takamori, S., Brunetti, L., et al.[2023]

In a study of 111 melanoma patients treated with immunotherapy or targeted therapy, the majority received immunotherapy, particularly anti-PD-1 treatments, with a total of 371 adverse events (AEs) reported.

The incidence of AEs was lower in patients receiving anti-PD-1 therapy, with only 15.3% experiencing severe (grade 3 to 4) AEs, which were more common in those on targeted therapies, highlighting the need for better reporting and understanding of both known and unknown AEs in cancer treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Using a cancer registry to capture signals of adverse events following immune and targeted therapy for melanoma. Aguiar, JP., Cardoso Borges, F., Murteira, R., et al.[2021]

A study of 236 patients receiving preoperative immunotherapy for non-small cell lung cancer showed that it is safe, with no significant differences in short-term outcomes like margin positivity, 30-day readmission, or mortality compared to 10,715 patients receiving preoperative chemotherapy.

Overall survival rates were similar between the immunotherapy group (63% at 5 years) and the chemotherapy group (51% at 5 years), indicating that immunotherapy is a feasible option before surgery without compromising patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Perioperative Outcomes and Survival After Preoperative Immunotherapy for Non-Small Cell Lung Cancer. Mayne, NR., Potter, AL., Bharol, K., et al.[2022]

A study of 17 patients undergoing various surgeries while receiving immune checkpoint inhibitors (ICI) showed no severe complications (Grade III-IV) in the 30 days post-surgery, suggesting that ICI are safe in the perioperative setting.

The findings indicate that ICI, including pembrolizumab and ipilimumab, do not need to be discontinued during surgery, although further research is needed to confirm these results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Feasibility and Safety of Surgery in Patients Receiving Immune Checkpoint Inhibitors: A Retrospective Study. Elias, AW., Kasi, PM., Stauffer, JA., et al.[2022]

Surgery is the primary treatment for patients with localized melanoma (stages 0-II), involving wide excision and sentinel lymph node biopsy when necessary.

For stage III melanoma, surgery is preferred for patients with limited metastases, but the use of effective preoperative drugs should be considered, while stage IV melanoma management should involve a multidisciplinary team for optimal decision-making.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Surgical management of melanoma. Sondak, VK., Gibney, GT.[2014]

The combination of ipilimumab and nivolumab, when given before surgery, significantly enhances the immune response against advanced melanoma, leading to a high rate of complete tumor response.

In a reported case, this pre-surgical treatment increased the presence of CD8+ T cells in the tumor area, suggesting a stronger anti-tumor immune activity, making it a promising approach for patients with unresectable advanced melanoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Successful Treatment of Unresectable Advanced Melanoma by Administration of Nivolumab With Ipilimumab Before Primary Tumor Resection. Fujimura, T., Kambayashi, Y., Sato, Y., et al.[2020]

Recent advancements in melanoma surgery have shifted from highly radical procedures with many complications to less invasive operations, improving patient outcomes.

The introduction of new systemic treatments, including targeted therapies and immunotherapy, has redefined the role of surgery in melanoma treatment, particularly reducing the need for extensive surgeries like elective block dissections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Surgery for malignant melanoma - Expected standards]. Kádár, Z., Lengyel, Z., Gyulai, R.[2023]

Surgical resection is often curative for early cutaneous melanoma, but some patients may experience relapse due to high-risk features in their tumors or lymph nodes.

Immunotherapy using checkpoint inhibitors like ipilimumab, nivolumab, and pembrolizumab has been shown to improve recurrence-free survival in patients with node-positive melanoma after surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adjuvant immunotherapy for melanoma. Thomas, D., Bello, DM.[2021]

References

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

Neoadjuvant Immune Checkpoint Inhibitor Therapy in Melanoma: Efficacy, Safety and Timing. [2022]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Preoperative Therapy in Melanoma: Evolving Perspectives in Clinical Trials. [2023]

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

Surgical Utilization and Outcomes for Patients with Stage IV Melanoma in the Modern Immunotherapy Era. [2023]

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

Use of immunotherapy and surgery for stage IV melanoma. [2021]

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

Current Immunotherapy Practices in Melanoma. [2020]

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

The price of tumor control: an analysis of rare side effects of anti-CTLA-4 therapy in metastatic melanoma from the ipilimumab network. [2022]

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

Impact of Neoadjuvant Immune Checkpoint Inhibitors on Surgery and Perioperative Complications in Patients With Non-small-cell Lung Cancer: A Systematic Review. [2023]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Using a cancer registry to capture signals of adverse events following immune and targeted therapy for melanoma. [2021]

9. Netherlands pubmed.ncbi.nlm.nih.gov

Perioperative Outcomes and Survival After Preoperative Immunotherapy for Non-Small Cell Lung Cancer. [2022]

10. Switzerland pubmed.ncbi.nlm.nih.gov

The Feasibility and Safety of Surgery in Patients Receiving Immune Checkpoint Inhibitors: A Retrospective Study. [2022]

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

Surgical management of melanoma. [2014]

12. Switzerland pubmed.ncbi.nlm.nih.gov

Successful Treatment of Unresectable Advanced Melanoma by Administration of Nivolumab With Ipilimumab Before Primary Tumor Resection. [2020]

13. Hungary pubmed.ncbi.nlm.nih.gov

[Surgery for malignant melanoma - Expected standards]. [2023]

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

Adjuvant immunotherapy for melanoma. [2021]